KR900002065B1

KR900002065B1 - Process for preparing brasinoride analogues

Info

Publication number: KR900002065B1
Application number: KR1019860000414A
Authority: KR
Inventors: 조광연; 허만욱; 김영섭
Original assignee: 재단법인 한국화학연구소; 채영복
Priority date: 1986-01-23
Filing date: 1986-01-23
Publication date: 1990-03-31
Also published as: KR870006836A

Abstract

The method for preparing brasinoride analogues or formula (I), useful as plant growth regulator, is presented. Thus, 18.0g of p- toluenesulfonyl chloride is added to 200ml of the solution having 15g of stigmasterol. The above mixture solution is reacted at the room temperature for 12 hrs and the reacted solution is added to 1 litre of 5% sodium bicarbonate solution. The obtained precipitates are filtered, washed with water and dried at below 60≰C under vaccum. The above solid is re-crystalized to make the white stigmasterol-3- tosilate. In (I), R is H, C1-10 aliphatic gp., cyclo or aromatic gp.

Description

브라시노라이드 유사체의 제조방법Method of Making Brassinolide Analogues

본 발명은 신규의 브라시노라이드 유사체의 제조방법에 관한 것이다. 특히 본 발명은 식물 생장 조절제로서 유용한 하기 일반식(I)의 브라시노라이드 유사체의 제조방법에 관한 것이다.The present invention relates to a process for the preparation of novel brassinolide analogs. In particular, the present invention relates to a process for the preparation of brassinolide analogues of general formula (I) below useful as plant growth regulators.

상기 식중, R은 수소, 탄소수 1∼10개의 직쇄 지방족기, 탄소수 3∼10개의 측쇄 지방족기, 시클로기, 메틸메틸술피닐기, 에톡시메틸기 1∼3개의 저급알킬기로 치환되어도 좋은 방향족 또는 복소환기를 나타낸다.In the above formula, R is an aromatic or heterocyclic group which may be substituted with hydrogen, a linear aliphatic group of 1 to 10 carbon atoms, a branched aliphatic group of 3 to 10 carbon atoms, a cyclo group, a methylmethylsulfinyl group or a lower alkyl group of 1 to 3 ethoxymethyl groups. Indicates.

상기 일반식(I)화합물의 기에 대한 설명중, 직쇄 지방족기란 탄소수 1∼10의 알킬기, 탄소수 2∼10의 알케닐을 의미하며, 측쇄지방족기란 이소프로필, 이소부틸, 이소펜틸, 이소헥실, 이소헵틸, 이소옥틸, sec-부틸, sec-펜틸, sec-헥실, sec-헵틸, sec-옥틸, ter-아밀, ter-헥실, ter- 헵틸, ter-옥틸기를 의미한다. 또한 시클로기란 탄소수 3∼10의 시클로알킬기, 시클로알케닐기, 시클로알킬저급알킬기를 나타낸다.In the description of the group of the general formula (I), the straight chain aliphatic group means an alkyl group having 1 to 10 carbon atoms and an alkenyl having 2 to 10 carbon atoms, and the side chain aliphatic group is isopropyl, isobutyl, isopentyl, isohexyl, iso Heptyl, isooctyl, sec-butyl, sec-pentyl, sec-hexyl, sec-heptyl, sec-octyl, ter-amyl, ter-hexyl, ter-heptyl, ter-octyl group. In addition, a cyclo group represents a C3-C10 cycloalkyl group, a cycloalkenyl group, and a cycloalkyl lower alkyl group.

방향족기란 페닐기, 1∼3개의 저급알킬기가 치환된 페닐기, 벤질기, 1∼3개의 저급알킬기가 치환된 벤질기, 페닐에테닐기, 페닐저급알킬기, 1∼3개의 저급알킬기가 치환된 페닐 저급알킬기 등을 나타내며, 1∼3개의 저급알킬기로 치환되어도 좋은 복소환기란 피리딜기, 1∼3개의 저급알킬기로 치환된 피리딜기, 푸라닐기, 1∼3개의 저급알킬기로 치환된 푸라닐기, 푸라닐저급알킬기, 옥사졸기, 이소옥사졸기, 저급알킬기로 치환된 이소옥사졸기, 옥사졸저급알킬기, 티오페닐기, 저급알킬기로 치환된 티오페닐기, 티오페닐저급알킬기, 티오피라닐기 등을 나타낸다.The aromatic group is a phenyl group, a phenyl group substituted with 1 to 3 lower alkyl groups, a benzyl group, a benzyl group substituted with 1 to 3 lower alkyl groups, a phenyl lowerenyl group, a phenyl lower alkyl group and a lower phenyl substituted with 1 to 3 lower alkyl groups Heterocyclic group which may represent an alkyl group etc. and may be substituted by 1-3 lower alkyl groups is a pyridyl group, the pyridyl group substituted by 1-3 lower alkyl groups, furanyl group, the furanyl group substituted by 1-3 lower alkyl groups, furanyl An isoxazole group substituted with a lower alkyl group, an oxazole group, an isoxazole group, a lower alkyl group, an oxazole lower alkyl group, a thiophenyl group, a thiophenyl group substituted with a lower alkyl group, a thiophenyl lower alkyl group, a thiopyranyl group, etc. are shown.

하기 일반식(A)의 브라시노라이드 화합물은 1979년 미국의 클로브 등에 의해 유채의 화분으로부터 처음으로 분리된 화합물로서(Nature, 281, 216, 1979)식물 생육촉진물질이며, 이는 1980년 풍등이 입체선택적으로 합성했다.[J. Am. Chem. Soc., 102, 6580(1980)]The brassinolide compound of the following general formula (A) is the first compound isolated from pollen of rapeseed (Nature, 281, 216, 1979) by Clove et al in 1979 (Nature, 281, 216, 1979). Selectively synthesized. [J. Am. Chem. Soc., 102, 6580 (1980)].

그후, 이 화합물이 식물의 생장에 미치는 효과가 여러면에서 검토되었다.(Chem. ＆ Eng. News, Nov. 5, 20, 1979) 브라시노라이드는 강력한 식물 생장 촉진 효과를 갖는다고 보고되어 있으며, 이는 식물 세포의 길이 생장과 세포분열의 촉진에 의한 것으로 밝혀졌다. 이들 물질은 극히 낮은 농도(1×10^-4㎍/ml)에서도 효과가 있다고 보고되어 왔다. [Agric. Bio. Chem, 48(3), 719∼726, 1984, ibid 47(5), 1139∼1141, 1983] 현재 이런 종류의 화합물들을 농업에 이용하려는 시도가 미국, 일본, 유럽 등에서 널리 행하여지고 있으며 상당히 성공적인 결과들이 보고되고 있다.Thereafter, the effect of this compound on plant growth has been examined in many ways (Chem. & Eng. News, Nov. 5, 20, 1979). Brassinolide has been reported to have a potent plant growth promoting effect. This was found to be due to the growth of plant cells and the promotion of cell division. These substances have been reported to be effective at extremely low concentrations (1 × 10 ⁻⁴ μg / ml). Agric. Bio. Chem, 48 (3), 719 to 726, 1984, ibid 47 (5), 1139 to 1141, 1983. Attempts to use these kinds of compounds in agriculture are now widely undertaken in the United States, Japan, and Europe, and with significant success. Are being reported.

첫번째 시도는 보통식물보다 더 빠르게 꽃이 피고 열매가 맺으며, 빨리 익게하는 시도가 벼, 딸기, 양상치, 대두콩과 보리 등에 행하여 졌으며, 이 실험 결과, 이들 브라시노라이드가 유묘상태의 식물에 대해, 태양광을 좀더 효과적으로 이용케하는 것으로 믿어지고 있다. 이제 막 싹이 트는 식물체의, 약 1에이커의 면적에 1mg정도만 뿌려도 조기 수확 등의 목표를 달성할 수 있는 것으로 믿어져, 우리나라와 같은 비교적 북쪽에 위치한 지방들(캐나다, 알래스카)에서 수확기를 단축함으로서 생산량을 증대시킬수 있으며, 비교적 따뜻한 나라에선, 1번 더 수확할 수 있는 가능성을 제시한다고 볼 수 있다.The first attempts were to flower and fruit faster than ordinary plants, and to ripen early, such as rice, strawberries, lettuce, soybeans, and barley. It is believed to use sunlight more effectively. It is believed that just 1 milligram of acres of newly sprouted plants can achieve the goal of early harvesting, and by shortening the harvesting season in relatively northern provinces like Canada and Alaska. It is possible to increase yields and, in a relatively warm country, offers the possibility of one more harvest.

둘째로, 브라시노라이드는 식물체가 잡초와 곤충, 질병 그리고 그 외의 여러 불리한 환경적인 요건(서리, 가뭄)에 가장 취약한 시기인 유묘시기에 이를 강하게 하여 주기 때문에, 최종 산물의 상태가 좋고, 더욱 커질 수 있다. 브라시노라이드로 처리할 경우, 뿌리가 굳건해져(예, 딸기, 토마토, 콩에서), 조기 수확뿐만 아니라, 노화도 늦추어 주는 것으로 믿어지고 있다. 실제 미국 농무성의 연구팀의 연구 결과로는 몇몇 작물에서 약 15%∼20%의 증수가 있었고, 감자의 눈에 발라준 결과 그 크기가 커져 시장에서의 인기가 좋았다고 하며, 콩의 온실 실험에선 32%나 증수가 있었다고 한다.Second, because brassinolide strengthens it during the seedling season, when plants are most vulnerable to weeds, insects, diseases and other adverse environmental requirements (frost, drought), the final product is in good condition and grows larger. Can be. When treated with brassinolide, it is believed that the roots are firm (eg from strawberries, tomatoes and beans), which slow down aging as well as early harvest. In fact, the US Department of Agriculture's research team found that some crops had about 15% to 20% increase, and the size of the potato's eye showed its size and popularity in the market. I said there was some increase.

이 화합물들은 그 후 연구 결과[T. Morishita, H. Abe, M. Uchiyama, S. Marumo, S. Takatsuto and N. Ikekawa, Phytochem., 22, 1051(1983) S. Takatsuto, B. Ying, M. Morisaki and N. Ikekawa, J. Chromatogr., 239, 233(1982) M. Ikeda, S. Takatsuto, T. Sassa, N. Ikekawa and M. Nukina, Agric Biol. Chem., 47, 655(1983) T. Yokota, J. Baba and N. Takahashi, Tetrahedron Lett., 23, 4965(1982) H. Abe, I. Morishita, M. Uchiyama, S. Marumo, K. Munakata, S. Takatsuto and M. Ikekawa, Agric. Biol. Chem., 46, 2609(1982) H. Abe, T. Morishita, M. Uchiyama, S. Takatsuto, N. Ikekawa, M. Ikeda, T. Sassa, T. Kitsuwa and S. Marumo, Experientia, 39, 351(1983) T. Yokota, M. Arima and N. Takahashi, Tetrahedron Lett., 23, 1275(1982) J. Baba, T. Yokota and N. Takahashi, Agric. Biol. Chem., 47. 659(1983) T. Yokoda, J. Baba and N. Takahashi, Agric. Biol. Chem., 47. 1409(1983) T. Yokota, M. Arima, N. Takahashi, S. Takatsuto, N. Ikekawa, T. Takematsu, Agric. Biol. Chem., 47(10), 2419∼2420(1983)]에 의하면, 자연계에도 널리 존재하는 것으로 알려져 있으며, 앞으로 농업적인 면에서 광범위한 응용이 기대되고 있는 화합물이다. 그러나, 이 화합물은, 그 구조에서 알 수 있듯이, 7개의 키랄 중심(Chiral Center)을 가지고 있으며, 그 구조가 복잡하여 대량 생산에 문제가 있으며, 자연 상태에서 불안정하여 쉽게 그 효과를 상실하는 결점을 가지고 있다.These compounds have since been studied [T. Morishita, H. Abe, M. Uchiyama, S. Marumo, S. Takatsuto and N. Ikekawa, Phytochem., 22, 1051 (1983) S. Takatsuto, B. Ying, M. Morisaki and N. Ikekawa, J. Chromatogr , 239, 233 (1982) M. Ikeda, S. Takatsuto, T. Sassa, N. Ikekawa and M. Nukina, Agric Biol. Chem., 47, 655 (1983) T. Yokota, J. Baba and N. Takahashi, Tetrahedron Lett., 23, 4965 (1982) H. Abe, I. Morishita, M. Uchiyama, S. Marumo, K. Munakata , S. Takatsuto and M. Ikekawa, Agric. Biol. Chem., 46, 2609 (1982) H. Abe, T. Morishita, M. Uchiyama, S. Takatsuto, N. Ikekawa, M. Ikeda, T. Sassa, T. Kitsuwa and S. Marumo, Experientia, 39, 351 (1983) T. Yokota, M. Arima and N. Takahashi, Tetrahedron Lett., 23, 1275 (1982) J. Baba, T. Yokota and N. Takahashi, Agric. Biol. Chem., 47. 659 (1983) T. Yokoda, J. Baba and N. Takahashi, Agric. Biol. Chem., 47. 1409 (1983) T. Yokota, M. Arima, N. Takahashi, S. Takatsuto, N. Ikekawa, T. Takematsu, Agric. Biol. Chem., 47 (10), 2419-2420 (1983), are widely known to exist in the natural world, and are widely expected to be used for agricultural applications in the future. However, this compound, as its structure shows, has seven chiral centers, its structure is complex, which causes problems in mass production, and is unstable in nature and easily loses its effect. Have.

본 발명자들은 식물에 대해 브라시노라이드와 같은 생리적인 효과를 가지고 있으면서도, 합성이 용이하고, 생산 가격이 저렴한 화합물을 개발하기 위하여, 예의 연구를 한 결과, 브라시노라이드의 측쇄가 생물학적 활성을 좌우하는 중요한 인자임을 발견하였다. 즉, 측쇄의 길이가 탄소사슬로 볼때 3개 내지 5개의의 범위에 있어야 하며, 적절한 소수성을 갖어야 하는 것이다. 따라서 이의 요구도를 충족하는 여러 화합물들을 제조하였고, 특히 방향족 화합물을 측쇄에 도입한 화합물들도 제조하였다. 이들 화합물들에 대해 라미나조인트 법으로 실험한 결과, 강력한 생리 활성을 가지고 있음을 발견하고 본 발명을 완성하게 되었다.The present inventors have conducted intensive studies to develop compounds that have a physiological effect such as brassinolide on plants, but are easy to synthesize and have low production cost. It was found to be an important factor. That is, the length of the side chain should be in the range of 3 to 5 in terms of carbon chain, and should have appropriate hydrophobicity. Therefore, several compounds were produced that fulfilled the requirements thereof, and in particular, compounds in which aromatic compounds were introduced into the side chain. Experiments with these compounds by the lamina joint method revealed that they have strong physiological activity and have completed the present invention.

본 발명은 신규의 상기 일반식(I) 브라시노라이드 유사체의 제조방법을 제공하는데 있다.The present invention provides a novel method for preparing the general formula (I) brassinolide analogue.

이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.

본 발명을 하기 일반식(II) 6, 6-에틸렌-2α, 3α-이소프로필렌-디옥시-5α-프레그난-20S-카르복스알데히드롤 그리나드 시약과 같은 유기 금속 화합물 등의 화합물과 반응시켜 하기 일반식(III)의 화합물을 제조한 다음, 이의 보호기를 제거하여 상기 일반식(I) 화합물을 제조하는 방법에 관한 것이다.The present invention is reacted with a compound such as an organometallic compound such as the following general formula (II) 6, 6-ethylene-2α, 3α-isopropylene-dioxy-5α-pregnan-20S-carboxaldehyde roll Grignard reagent The present invention relates to a process for preparing the compound of formula (I) by preparing a compound of formula (III), followed by removal of its protecting group.

상기 식중 R은 전술한 바와 같다. 상기 일반식(II)의 화합물은 하기의 합성 경로에 따라 제조될 수 있다.Wherein R is as described above. The compound of formula (II) may be prepared according to the following synthetic route.

상기 일반식(II)화합물의 제조방법도 신규하며 본 발명의 범위에 속한다. 합성 공정 중 온도, 용매 등의 조건은 절대적인 수치가 아니고 바람직한 조건을 나타냄은 말할나위도 없다. 상기 합성 경로를 약술하여 명백히 한다. 상업적으로 쉽게 구할 수 있는 스티그마스테롤(IV)을 피리딘 속에서 p-톨루엔술포닐클로라이드로 반응시켜 스티그마스테롤-3-토실데이트(V)를 얻는다. 이를 용매화 분해하여 i-스티그마스테롤(VI)을 만든다음, 피리딘-삼산화크롬으로 산화하여 6-케토화합물(VII)을 얻은 다음 술포란을 용매로 하여 톨루엔 술포닐히드록시드로 재배열(rearrangement) 시키면 2,22-디엔 화합물(VIII)가 얻어진다. 이것을 아세톤을 용매로 하여 건조 질소하에서 촉매 오스밀화 반응(Osmylation) 시키면, 2,3-디히드록시-22-엔-5α-스티그마스톤-6-온(IX)이 얻어진다. 이를 히드록시기와 케톤기 부분을 보호한 후에, -70℃에서 오존으로 2중 결합을 잘라서 상기 출발물질인 알데히드(II)를 얻는다.The preparation method of the above general formula (II) compound is also novel and belongs to the scope of the present invention. It is needless to say that the conditions such as temperature, solvent, etc. during the synthesis process are not absolute values and indicate preferable conditions. The synthetic route is outlined and made clear. Commercially readily available stigmasterol (IV) is reacted with p-toluenesulfonylchloride in pyridine to give stigmasterol-3-tosyldate (V). This was subjected to solvation to form i-stigmasterol (VI), which was then oxidized to pyridine-chromium trioxide to give 6-keto compound (VII), followed by rearrangement with toluene sulfonyl hydroxide with sulfolane as solvent. 2,22-diene compound (VIII) is obtained. When this is subjected to catalytic ossylation reaction under dry nitrogen using acetone as a solvent, 2,3-dihydroxy-22-ene-5α-sigmastone-6-one (IX) is obtained. After protecting the hydroxyl group and the ketone group moiety, the double bond is cleaved with ozone at −70 ° C. to obtain the starting aldehyde (II).

[실시예 1]Example 1

스티그마스테릴-3-토실레이트(V)의 제조Preparation of stigmasteryl-3-tosylate (V)

p-톨로엔술포닐클로라이드(18.0gr)을 건조피리딘(200ml)에 녹인 스티그마스테롤(15.0gr)의 용액에 가한다. 위의 반응혼합물을 상온의 암실에서 12시간 반응을 시킨 다음, 5%의 중탄산칼륨 수용액 1l에 교반을 시키면서 서서히 붓는다. 이때 생성되는 고형상의 침전물을 여과하고, 침전물에 묻은 피리딘을 제거하기 위해 수회 물로 씻은 다음 감압하 그리고 60℃ 이하에서 건조시킨다. 무수아세톤에서 재결정을 한다. 결정은 흰색이다. 수율은 정량적이다.p-Toloenesulfonylchloride (18.0 gr) is added to a solution of stigmasterol (15.0 gr) dissolved in dry pyridine (200 ml). The reaction mixture was reacted for 12 hours in a dark room at room temperature, and then slowly poured while stirring in 1 l of 5% aqueous potassium bicarbonate solution. The resulting solid precipitate is filtered off, washed several times with water to remove pyridine from the precipitate, and then dried under reduced pressure and below 60 ° C. Recrystallize from anhydrous acetone. The crystal is white. Yield is quantitative.

융점 : 132∼133℃Melting Point: 132 ~ 133 ℃

NMR, δ(60MHz, CDCl₃/TMS) : 0.67, 0.73, 0.78, 0.83, 0.87(CH₃), 1.04∼2.40(CH₂-, CH-), 2.42(3H, CH₃-C₆H₄-), 4.0∼4.58(1H, bs), 4.95∼5.18(2H, m) 5.18∼5.43(1H, m), 7.2∼7.92(4H, q, J₁=23Hz, J₂=8Hz)NMR, δ (60MHz, CDCl ₃ / TMS): 0.67, 0.73, 0.78, 0.83, 0.87 (CH ₃ ), 1.04-2.40 (CH _2- , CH-), 2.42 (3H, CH ₃ -C ₆ H _4- ), 4.0 to 4.58 (1H, bs), 4.95 to 5.18 (2H, m) 5.18 to 5.53 (1H, m), 7.2 to 7.92 (4H, q, J ₁ = 23 Hz, J ₂ = 8 Hz)

I. R, (KBr-pellet) νmax(CM^-1) : 2930(s), 2840(s), 1695(w), 1495(w), 1465(m), 1440(m), 1390(m), 1370(m), 1360(s), 1320(w), 1305(w), 1298(w), 1270(w), 1200(s), 1180(s), 1143(w), 1125(w), 1105(m), 1025(w), 1015(W), 1000(w), 980(s), 950(s), 938(m), 900(s), 880(s), 878(m), 855(m), 830(s), 810(m), 805(m), 790(w), 755(w), 708(w), 742(w), 708(w), 680(s), 640(w), 60(w), 565(s).I. R, (KBr-pellet) ν max (CM ^-1 ): 2930 (s), 2840 (s), 1695 (w), 1495 (w), 1465 (m), 1440 (m), 1390 (m) , 1370 (m), 1360 (s), 1320 (w), 1305 (w), 1298 (w), 1270 (w), 1200 (s), 1180 (s), 1143 (w), 1125 (w) , 1105 (m), 1025 (w), 1015 (W), 1000 (w), 980 (s), 950 (s), 938 (m), 900 (s), 880 (s), 878 (m) , 855 (m), 830 (s), 810 (m), 805 (m), 790 (w), 755 (w), 708 (w), 742 (w), 708 (w), 680 (s) , 640 (w), 60 (w), 565 (s).

[실시예 2]Example 2

i-스티그마스테롤의 제조Preparation of i-Stig Masterol

스티그마스테롤-3-토실레이트(5.5gr)와 중탄산칼륨(3.2gr)을 아세톤(2l)에 녹인 다음, 물(200ml)을 여기에 더한다. 위의 반응 혼합물을 1시간 동안 환류 시킨 다음, 아세톤을 약 3시간에 걸쳐서 증류해서 제거 한다. 잔여반응물을 상온으로까지 냉각 시킨 후, 에테르로 추출한다. 추출된 유기용매층을 물, 포화소금물 등으로 순차적으로 씻은 다음, 무수 황산마그네슘으로 건조한다. 감압하에서 용매를 제거하여 굳기름 상태의 다소 불순한 i-스티그마스테롤이 정량적으로 얻어졌다. 이를 더 이상의 정제화하는 조작이 없이 다음에 쓰여졌다. 왜냐하면 이때의 불순물들이 다음 반응이 끝난 후에 제거될 수 있었기 때문이다. 반응의 진행에 관한 정보를 얻기 위해, 분석용 시료를 컬럼 크로마트그래피를 통하여 얻었다.[고형상은 플로리실(florisil), 전개 용매는 석유에테르와 벤젠을 2 대 3의 비율로 사용]Dissolve stigmasterol-3-tosylate (5.5 gr) and potassium bicarbonate (3.2 gr) in acetone (2 l), then add water (200 ml) to it. The reaction mixture was refluxed for 1 hour and then the acetone was distilled off over about 3 hours. The remaining reactant is cooled to room temperature and then extracted with ether. The extracted organic solvent layer is washed sequentially with water, saturated brine and the like, and then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give quantitatively somewhat impure i-Stigmasterol in a solid oil state. It is written next without further refinement. This is because impurities at this time could be removed after the next reaction. To obtain information on the progress of the reaction, analytical samples were obtained by column chromatography. [The solid phase used florisil and the developing solvent used petroleum ether and benzene in a ratio of 2 to 3].

융점 : 50∼53℃Melting Point: 50 ~ 53 ℃

NMR : δ(60MHz, CDCl₃/TMS); 0.65∼2.6(m, singlets at 0.73, 0.90, 0.97, 1.06), 3.10∼3.50(1H, bs), 4.85∼5.15(2H, m)NMR: δ (60 MHz, CDCl ₃ / TMS); 0.65 to 2.6 (m, singlets at 0.73, 0.90, 0.97, 1.06), 3.10 to 3.50 (1H, bs), 4.85 to 5.15 (2H, m)

IR(KBr-pellet), νmax(cm^-1); 3425(m), 2925(s), 2830(s), 1470(m), 1460(m), 1400(w), 1382(m), 1350(w), 1365(m), 1285(w), 1065(w), 1055(w), 1023(m), 1010(w), 980(m), 935(w), 880(w), 820(w), 620(w).IR (KBr-pellet), ν max (cm ⁻¹ ); 3425 (m), 2925 (s), 2830 (s), 1470 (m), 1460 (m), 1400 (w), 1382 (m), 1350 (w), 1365 (m), 1285 (w), 1065 (w), 1055 (w), 1023 (m), 1010 (w), 980 (m), 935 (w), 880 (w), 820 (w), 620 (w).

[실시예 3]Example 3

24-s-에틸-3α,5-시클로-5α-콜로스트-22-엔-6-온의 제조Preparation of 24-s-ethyl-3α, 5-cyclo-5α-colost-22-en-6-one

i-스티그마스테롤(6.0gr)을 피리딘(80ml)에 녹인다. 여기에 삼산화크롬(6.0gr)을 서서히 더한다. 위의 반응 혼합물을 상온에서 2시간 교반한다. 이때 기벽에 부착되는 물질들을 약수저를 사용 긁어내어 미세한 상태로 만든다. 연 후에 에테르(80ml)를 붓고 잘 교반하면 많은 양의 고운 침전물이 유리됨을 볼 수 있다. 이들을 여과하고, 여과안된 물질을 에티르로 씻은 다음, 모아진 여액에 얼음을 넣어 차게 만든 다음 6N-염산을 넣어서 잘 교반한 후에, 유기층과 수용액층으로 각각 분리한다. 수용액층을 2번 더, 에테르로 추출한다. 합하여진 에테르 층을 얼음을 넣어 차게 만든 후 포화 중탄산나트륨 수용액으로 씻고, 함염수로 씻은 후, 감압하에서 용매를 제거한다. 이렇게 해서 얻어진 물질을 컬럼 크로마토그래피를 한다. 이때 고정상은 실리카 겔 60G, 70∼200메쉬이며, 헥산으로 고정상을 채운 후, 헥산 : 벤젠= 1 : 1의 용매 혼합물로 전개 시킨다. 이때 85%의 수율로 5.05gr이 얻어졌다. 이를 99% 에탄올에서 재결정하니 흰색의 결정이 얻어졌다.Dissolve i-Stigmasterol (6.0 gr) in pyridine (80 ml). Chrome trioxide (6.0 gr) is slowly added thereto. The reaction mixture is stirred at room temperature for 2 hours. At this time, the material attached to the base wall is scraped off using a weak spoon to make a fine state. After opening, pour ether (80 ml) and stir well to see that a large amount of fine precipitate is liberated. They are filtered, the unfiltered material is washed with ethyr, iced in the collected filtrate, and then stirred well by adding 6N hydrochloric acid, and then separated into an organic layer and an aqueous layer. The aqueous layer is extracted twice more with ether. The combined ether layers are cooled with ice, washed with saturated aqueous sodium bicarbonate solution, washed with brine and the solvent is removed under reduced pressure. The material thus obtained is subjected to column chromatography. At this time, the stationary phase is silica gel 60G, 70-200 mesh, and after filling the stationary phase with hexane, it is developed with a solvent mixture of hexane: benzene = 1: 1. At this time, 5.05 gr was obtained with a yield of 85%. It was recrystallized in 99% ethanol to obtain white crystals.

융점 : 100.5∼101.5℃Melting Point: 100.5 ~ 101.5 ℃

NMR δ(60MHz, CDCl₃/TMS); 0.73, 0.80, 0.86, 0.90, 1.02, 1.10(18H, CH₃), 1.1∼2.7(26H, CH₂, CH), 5.0∼5.5(2H, m)NMR δ (60 MHz, CDCl ₃ / TMS); 0.73, 0.80, 0.86, 0.90, 1.02, 1.10 (18H, CH ₃ ), 1.1 to 2.7 (26H, CH ₂ , CH), 5.0 to 5.5 (2H, m)

; 2900(s), 2830(s), 1680(s), 1460(s), 1415(w), 1320(w), 1310(m), 1300(s), 1700(w), 1160(w), 1130(w), 1120(w), 1110(w), 1080(w), 1065(w), 1050(w), 1030(w), 1010(w), 980(s), 950(w), 910(w), 880(w), 820(w), 640(w).

; 2900 (s), 2830 (s), 1680 (s), 1460 (s), 1415 (w), 1320 (w), 1310 (m), 1300 (s), 1700 (w), 1160 (w), 1130 (w), 1120 (w), 1110 (w), 1080 (w), 1065 (w), 1050 (w), 1030 (w), 1010 (w), 980 (s), 950 (w), 910 (w), 880 (w), 820 (w), 640 (w).

[실시예 4]Example 4

24-s-에틸-5α-콜레스타-2,22-디엔-6-온의 제조Preparation of 24-s-ethyl-5α-cholesta-2,22-diene-6-one

24s-에틸-3α,5-시클로-5α-콜레스트-22-엔-6-온(12gr)을 술포란(86ml)에 녹인 용액에, p-톨루엔술폰산(617mg)을 가한다. 위의 반응 혼합물 상부의 공기를 질소로 충진한 후에 서서히 질소를 불어 넣어 주면서, 160℃ 부근에서 약 90분간을 교반하여 준다. 이때, 반응액의 색깔이 약한 적색을 띄우게 된다. 반응 혼합물을 방치하여 냉각시켜 70∼80℃ 정도까지 내려왔을때, 약 80ml의 물을 서서히 가한다. 이때 용액에 불용성인 담황색의 고체들이 유리됨을 관찰할 수 있다. 이를 30분간 더 교환한 후에 여과하여, 고체를 취한다. 여액에 대해선, 물(80ml)을 더 첨가한 후에 번젠과 톨루엔을 1:1로 혼합한 용매로 추출한 후에 분리된 유기층을 물로 씻은 후, 분리한 고체와 합한다. 이렇게 해서 얻어진 유기층을 감압하에서 용매를 제거한 후, 헥산에 녹인다. 헥산에 불용성인 성분은 술포란이므로 이를 스포이드를 이용 분리해 낸다. 헥산층을 감압하에서 농축한 후 컬럼 크로마토그래피를 이용 물질를 분리해 내었다.(실리카 겔 60g, 70∼200메쉬, 헥산으로 충진, 헥산 : 벤전=1 : 1로 전개). 7.9gr이 얻어졌다(수율 66%). 99% 에탄올에서 재결정 하였다.To a solution of 24s-ethyl-3α, 5-cyclo-5α-cholest-22-en-6-one (12gr) in sulfolane (86 ml), p-toluenesulfonic acid (617 mg) is added. After filling the air above the reaction mixture with nitrogen, the mixture is slowly blown with nitrogen and stirred for about 90 minutes at around 160 ° C. At this time, the color of the reaction solution is light red. When the reaction mixture was left to cool down to about 70-80 ° C., about 80 ml of water was slowly added. At this time, it can be observed that light yellow solids insoluble in the solution are released. It is further exchanged for 30 minutes and then filtered to take a solid. For the filtrate, water (80 ml) was further added, followed by extraction with a solvent mixed with burnen and toluene in a 1: 1 ratio, and then the separated organic layer was washed with water and then combined with the separated solid. After removing the solvent under reduced pressure, the organic layer thus obtained is dissolved in hexane. The component insoluble in hexane is sulfolane, so it is separated using a dropper. The hexane layer was concentrated under reduced pressure and the material was separated using column chromatography (60 g of silica gel, 70-200 mesh, filled with hexane, hexane: benzene = 1: 1). 7.9 gr was obtained (yield 66%). Recrystallized from 99% ethanol.

융점 : 112.5∼113.0℃Melting Point: 112.5 ~ 113.0 ℃

NMR δ(60Hz, CDCl₃/TMS); 0.69, 0.78, 0.84, 0.88, 0.96, 1.08(18H, CH₃-), 1.1∼2.5(24H, -CH_2-CH-), 5.10(2H, m), 5.60(2H, m).NMR δ (60 Hz, CDCl ₃ / TMS); 0.69, 0.78, 0.84, 0.88, 0.96, 1.08 (18H, CH _3- ), 1.1 to 2.5 (24H, -CH ₂ -CH-), 5.10 (2H, m), 5.60 (2H, m).

; 2950(s), 2860(s), 1710(s), 1665(w), 1480(m), 1470(m), 1450(m), 1400(m), 1342(w), 1315(w), 1310(w), 1280(w), 1250(w), 1205(w), 1200(w), 1180(w), 1150(w), 1130(w), 1097(w), 1040(w), 1020(w), 1000(m), 950(w), 840(w), 700(m), 640(w).

; 2950 (s), 2860 (s), 1710 (s), 1665 (w), 1480 (m), 1470 (m), 1450 (m), 1400 (m), 1342 (w), 1315 (w), 1310 (w), 1280 (w), 1250 (w), 1205 (w), 1200 (w), 1180 (w), 1150 (w), 1130 (w), 1097 (w), 1040 (w), 1020 (w), 1000 (m), 950 (w), 840 (w), 700 (m), 640 (w).

[실시예 5]Example 5

2α,3α-디히드록시-24s-에틸-5α-콜레스트-22-E-엔-6-온의 제조Preparation of 2α, 3α-dihydroxy-24s-ethyl-5α-cholest-22-E-en-6-one

24S-에틸-5α-콜레스타-22-디엔-6-온(12gr)을 아세톤(600ml)에 녹인 다음, t-부탄올(200ml)에 녹인 4산화오스뮴(600mg)N-메틸-모르포린 옥시드(12gr)과 물(20ml)을 순서대로 가한다. 위의 반응액 상부의 공기를 질소로 치환한 후에, 10시간 동안 교반한다. 이때 생성된 산물이 결정으로서 석출됨을 볼 수 있다. 반응 혼합물에 포화 중아황산 나트륨 용액을 과량으로 존재하는 4산화오스뮴을 파괴하기 위해 첨가한 후 2시간동안 교반한다. 침전된 결정들을 여과하여 모으고, 여지상의 물질들을 따뜻한 물로 3회 이상 씻어준다. 처음 여과한 후의 여액을 조금씩 30∼40℃이하에서 감압 농축후 물을 첨가한 후에 에틸 아세테이트로 추출한 다음, 이를 물과 소금물로 씻은 후 무수 황산마그네슘으로 건조 후 감압 증류하니 물질(IX)가 얻어졌다. 이를 헥산하에서 잘 으깨었더니 미세한 분말로 얻어졌다(12.4gr). 수율 95.5%24S-ethyl-5α-cholesta-22-diene-6-one (12gr) was dissolved in acetone (600 ml) and then osmium tetraoxide (600 mg) N-methyl-morpholine oxide dissolved in t-butanol (200 ml). (12gr) and water (20ml) are added in order. After replacing the air above the reaction solution with nitrogen, it is stirred for 10 hours. It can be seen that the produced product is precipitated as crystals. Saturated sodium bisulfite solution is added to the reaction mixture to destroy excess osmium tetraoxide and then stirred for 2 hours. The precipitated crystals are collected by filtration and the remaining material is washed three times or more with warm water. The filtrate after the first filtration was concentrated gradually under reduced pressure at 30 ~ 40 ℃ little by little after adding water, extracted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate and distilled under reduced pressure to obtain a substance (IX). . This was crushed well under hexane to give a fine powder (12.4 gr). Yield 95.5%

융점 : 204∼207℃Melting Point: 204 ~ 207 ℃

=3310(m), 2915(s), 2835(m), 1700(s), 1460(w), 1380(w), 1370(w), 1090(w), 1065(w), 1050(m), 1020(w), 980(m).

= 3310 (m), 2915 (s), 2835 (m), 1700 (s), 1460 (w), 1380 (w), 1370 (w), 1090 (w), 1065 (w), 1050 (m) , 1020 (w), 980 (m).

[실시예 6]Example 6

2α,3α-이소프로필리덴-디옥시-24s-에틸-5α-콜레스트-22-E-엔-6-온의 제조Preparation of 2α, 3α-isopropylidene-dioxy-24s-ethyl-5α-cholest-22-E-en-6-one

2α,3α-디히드록시-24s-에틸-5α-콜레스트-22-E-엔-6-온(7.0gr)을 디클로로메탈(180ml)에 가한 혼합물에 2, 2-디-메톡시프로판(20ml)과 p-톨루엔-술폰산(0.33gr)을 가한 다음, 상온에서 1시간 가량 교반한다. 여기에 탄산칼륨 분말을 더한 후 5분간 교반한 뒤에 포화 중탄산나트륨 수용액으로 씻고, 무수 황산마그네슘으로 건조한 후 감압 증류하여 용매를 제거하였다. 수율은 정량적이다. 99% 에탄올에서 재결정하였다.To a mixture of 2α, 3α-dihydroxy-24s-ethyl-5α-cholest-22-E-en-6-one (7.0 gr) to dichlorometal (180 ml), 2,2-di-methoxypropane ( 20 ml) and p-toluene-sulfonic acid (0.33 gr) were added, followed by stirring at room temperature for 1 hour. Potassium carbonate powder was added thereto, stirred for 5 minutes, washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and distilled under reduced pressure to remove the solvent. Yield is quantitative. Recrystallized from 99% ethanol.

융점 : 158 ∼159℃Melting Point: 158∼159 ℃

NMR δ(60MHz, CDCl₃/TMS); 0.60∼2.6(m, singlets at 0.69, 1.33, 1.49), 3.80∼4.40(2H, m), 4.95∼5.24(2H, m).NMR δ (60 MHz, CDCl ₃ / TMS); 0.60 to 2.6 (m, singlets at 0.69, 1.33, 1.49), 3.80 to 4.40 (2H, m), 4.95 to 5.44 (2H, m).

; 2900(s), 2825(s), 1700(s), 1620(w), 1450(m), 1440(w), 1380(s), 1360(s), 1300(w), 1243(s), 1215(s), 1170(w), 1100(w), 1060(s), 1040(m), 1020(m), 990(w), 975(w), 900(w), 850(w), 800(w), 595(w), 510(w).

; 2900 (s), 2825 (s), 1700 (s), 1620 (w), 1450 (m), 1440 (w), 1380 (s), 1360 (s), 1300 (w), 1243 (s), 1215 (s), 1170 (w), 1100 (w), 1060 (s), 1040 (m), 1020 (m), 990 (w), 975 (w), 900 (w), 850 (w), 800 (w), 595 (w), 510 (w).

[실시예 7]Example 7

6,6-에틸렌디옥시-2α,3α-이소프로필리덴디옥시-24s-에틸-5α-콜레스트-22-엔의 제조Preparation of 6,6-ethylenedioxy-2α, 3α-isopropylidenedioxy-24s-ethyl-5α-cholest-22-ene

p-톨루엔술폰산(0.05gr)을 2α,3α-이소프로필리덴디옥시-24s-에틸-5α-콜레스트-22-엔(3.5gr)을 부타논에틸렌케탈(60ml)에 녹인 용액에 더한다. 이 용액을 7시간 동안 환류시킨 다음, 벤젠(50ml)을 더한 후 1N-수산화나트륨 수용액으로 씻어준다. 이를 물, 함염수 등으로 씻고 무수 황산마그네슘으로 건조한 후 감압하에서 용매를 제거한다. 물질(XI)이 끈끈한 검상으로 얻어졌다(3.2gr, 84% 수율).p-toluenesulfonic acid (0.05gr) is added to a solution of 2α, 3α-isopropylidenedioxy-24s-ethyl-5α-cholest-22-ene (3.5gr) dissolved in butanone ethylene ketal (60 ml). The solution was refluxed for 7 hours, and then benzene (50 ml) was added, followed by washing with 1N aqueous sodium hydroxide solution. It is washed with water, brine, and the like, dried over anhydrous magnesium sulfate, and the solvent is removed under reduced pressure. Material (XI) was obtained with sticky gum (3.2gr, 84% yield).

NMR δ(60MHz, CDCl₃/TMS); 0.60∼2.60(m,singlets at 0.63, 1.80, 1.86, 1.96, 1.04, 1.23, 1.38), 3.65∼4.42(6H, m), 4.90∼5.28(2H, m).NMR δ (60 MHz, CDCl ₃ / TMS); 0.60 to 2.60 (m, singlets at 0.63, 1.80, 1.86, 1.96, 1.04, 1.23, 1.38), 3.65 to 4.42 (6H, m), 4.90 to 5.28 (2H, m).

; 2900(s), 2825(s), 1450(m), 1370(m), 1300(w), 1280(w), 1225(w), 1185(m), 1175(m), 1150(w), 1130(w), 1060(s),1050(s), 1020(w), 975(m), 915(m), 890(w), 870(w), 820(w), 780(w), 670(w), 650(w), 560(w).

; 2900 (s), 2825 (s), 1450 (m), 1370 (m), 1300 (w), 1280 (w), 1225 (w), 1185 (m), 1175 (m), 1150 (w), 1130 (w), 1060 (s), 1050 (s), 1020 (w), 975 (m), 915 (m), 890 (w), 870 (w), 820 (w), 780 (w), 670 (w), 650 (w), 560 (w).

[실시예 8]Example 8

6,6-에틸렌-2α, 3α-이소프로필리덴-디옥시-5α-프레그난-20s-카르복스알데히드(일반식(II)화합물)의 제조.Preparation of 6,6-ethylene-2α, 3α-isopropylidene-dioxy-5α-pregnane-20s-carboxaldehyde (General Formula (II) Compound).

물질(XI)(4.0gr : 6,6-에틸렌디옥시-2α, 3α-이소프로필리덴디옥시-24s-에틸-5α-콜레스트-22-E-엔)을 디클로로메탄(500ml)과 메탄올(500ml)의 혼합 용매에 녹여낸 후, 중탄산나트룸(4gr)을 넣은 후 온도를 -70∼-50℃로 낮춘 후 오존을 불어 넣는다. 반응 혼합물의 색깔이 엷은 푸른색을 띠우면, 오존 도입을 즉시 중단하고, 냉수욕을 제거한 후 질소를 불어 넣어 과량으로 녹아 있는 오존을 구축해 낸 다음 황화메틸(15ml)을 넣고 3시간 가량 교반시켜 준다. 이를 감압하에서 용매를 제거한 잔여물을 에테르로 추출하면, 검상의 표제 화합물 3.0gr이 얻어졌다(88.7%수율).Substance (XI) (4.0 gr: 6,6-ethylenedioxy-2α, 3α-isopropylidenedioxy-24s-ethyl-5α-cholest-22-E-ene) was converted into dichloromethane (500 ml) and methanol ( After dissolving in a mixed solvent of 500ml), add sodium bicarbonate (4gr), lower the temperature to -70 ~ -50 ℃, and then blow ozone. When the reaction mixture is light blue in color, stop the introduction of ozone immediately, remove the cold water bath, blow nitrogen to build up the dissolved ozone, add methyl sulfide (15 ml) and stir for about 3 hours. The solvent was removed under reduced pressure, and the residue was extracted with ether to give 3.0 gr of the title compound (88.7% yield).

NMR δ(60MHz, CDCl₃/TMS); 0.6∼2.6(m,singlets at 0.71, 1.83), 3.5∼4.35(6H, m), 9.47(1H,d, J₁=3Hz).NMR δ (60 MHz, CDCl ₃ / TMS); 0.6-2.6 (m, singlets at 0.71, 1.83), 3.5-4.35 (6H, m), 9.47 (1H, d, J ₁ = 3 Hz).

; 2670(w), 1715(s), 1460(s), 1450(m), 1370(s), 1340(m), 1305(m), 1285(m), 1230(m), 1190(s), 1175(s), 1150(w), 1130(w), 1060(s), 1050(s), 980(m), 950(w), 920(w), 890(w), 870(w), 820(w), 780(w), 670(w), 640(w), 580(w), 560(w).

; 2670 (w), 1715 (s), 1460 (s), 1450 (m), 1370 (s), 1340 (m), 1305 (m), 1285 (m), 1230 (m), 1190 (s), 1175 (s), 1150 (w), 1130 (w), 1060 (s), 1050 (s), 980 (m), 950 (w), 920 (w), 890 (w), 870 (w), 820 (w), 780 (w), 670 (w), 640 (w), 580 (w), 560 (w).

[실시예 9]Example 9

2α,3α-디히드록시-20-(1-히드록시에틸)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxyethyl) -5α-pregnan-6-one

출발물질인 일반식(II) 화합물(0.76gr)의 에테르 용액에 교반을 시키면서, 메틸마그네슘브로마이드(0.5ml, 10N 에테르용액)을 적가한 다음, 30분간 교반시켜 준후, 반응 온도를 40∼50℃까지 올린 후 1시간 더 반응을 시킨다. 이 반응 용액을 냉각시키면서, 10ml의 물을 적가한다. 이를 에테르로 추출한 후에, 묽은 염산으로 씻은 후, 함염수로 씻고, 무수 황산 마그네슘으로 건조 후에, 감압 증발시켰다(0.72g, 88%). 이를 컬럼크로마토그래피를 하여 정제한다(실리카겔, 70∼200메쉬, 헥산 : 에틸아세테이트=4 : 2)Methyl magnesium bromide (0.5 ml, 10N ether solution) was added dropwise while stirring to an ether solution of a compound of formula (II) (0.76 gr) as a starting material, and stirred for 30 minutes, and then the reaction temperature was 40 to 50 ° C. Raise it up and let it react for another hour. 10 ml of water is added dropwise while cooling the reaction solution. After extraction with ether, washed with dilute hydrochloric acid, followed by brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure (0.72 g, 88%). This was purified by column chromatography (silica gel, 70-200 mesh, hexane: ethyl acetate = 4: 2).

NMR (H, 60MHz, CDCl₃/TMS), δ(ppm); 0.55∼2.30(m,singlets at 0.57, 0.67, 0.77, 0.84, 0.97, 1.07, 1.15, 1.27), 3.57∼4.30(m,7H)NMR (H, 60 MHz, CDCl ₃ / TMS), δ (ppm); 0.55 to 2.30 (m, singles at 0.57, 0.67, 0.77, 0.84, 0.97, 1.07, 1.15, 1.27), 3.57 to 4.30 (m, 7H)

; 3400(m), 2900(s), 1455(m), 1440(m), 1380(m), 1325(w), 1305(w), 1300(w), 1280(w), 1270(w), 1260(w), 1240(w), 1230(w), 1205(w), 1195(m), 1170(m), 1150(m), 1120(m), 1090(s), 1060(s), 1040(s), 1025(m), 980(w), 960(w), 950(w), 930(w), 920(w), 905(w), 890(w), 870(w).

; 3400 (m), 2900 (s), 1455 (m), 1440 (m), 1380 (m), 1325 (w), 1305 (w), 1300 (w), 1280 (w), 1270 (w), 1260 (w), 1240 (w), 1230 (w), 1205 (w), 1195 (m), 1170 (m), 1150 (m), 1120 (m), 1090 (s), 1060 (s), 1040 (s), 1025 (m), 980 (w), 960 (w), 950 (w), 930 (w), 920 (w), 905 (w), 890 (w), 870 (w).

위의 화합물 0.5g을 테트라히드로푸란(20ml)에 녹인 후에, 6N 염산용액(5ml)을 더한 후 밤새도록 교반시킨 다음, 용매를 제거한다. 컬럼 크로마토그래피를 하여(실리카겔, 클로로포름 : 메탄올=40 : 1), 최종 물질을 얻고, 이를 헥산-에테르하에서 잘 문질러서 고형 물질을 얻는다.(0.29gr, 82.3%)After 0.5 g of the above compound was dissolved in tetrahydrofuran (20 ml), 6N hydrochloric acid solution (5 ml) was added and stirred overnight, and then the solvent was removed. Column chromatography (silica gel, chloroform: methanol = 40: 1) gives the final material, which is then rubbed well under hexane-ether to give a solid material (0.29gr, 82.3%).

융점 : 216∼219℃Melting Point: 216 ~ 219 ℃

원소분석(C₂₃H₃₈O₄)Elemental Analysis (C ₂₃ H ₃₈ O ₄ )

계산치(%) : C; 73.04, H; 10.05, O; 16.91Calculated (%): C; 73.04, H; 10.05, O; 16.91

실측치(%) : C; 72.23, H; 10.64, O; 17.02Found (%): C; 72.23, H; 10.64, O; 17.02

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.60, 2.40(m, singlets at 0.67, 0.75, 0.94, 1.10, 1.18, 1.25, 1.54), 2.53∼2.80(1H, m), 3.58∼4.10(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.60, 2.40 (m, singlets at 0.67, 0.75, 0.94, 1.10, 1.18, 1.25, 1.54), 2.53 to 2.80 (1H, m), 3.58 to 4.10 (3 H, m).

; 3410(s), 2960(s), 2880(m), 1725(s), 1470(m), 1465(m), 1440(m), 1430(m), 1385(m), 1335(m), 1280(m), 1260(w), 1230(w), 1200(w), 1190(w), 1150(w), 1110(m), 1100(m), 1075(m), 1050(m), 1040(m), 1005(m), 990(m), 920(w), 890(w), 865(w), 740(w), 705(w), 680(w), 655(w), 640(w), 595(w), 550(w).

; 3410 (s), 2960 (s), 2880 (m), 1725 (s), 1470 (m), 1465 (m), 1440 (m), 1430 (m), 1385 (m), 1335 (m), 1280 (m), 1260 (w), 1230 (w), 1200 (w), 1190 (w), 1150 (w), 1110 (m), 1100 (m), 1075 (m), 1050 (m), 1040 (m), 1005 (m), 990 (m), 920 (w), 890 (w), 865 (w), 740 (w), 705 (w), 680 (w), 655 (w), 640 (w), 595 (w), 550 (w).

[실시예 10]Example 10

2α,3α-디히드록시-20-(1-히드록시프로필)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxypropyl) -5α-pregnan-6-one

출발물질인 알데히드(0.76g)의 에테르 용액에 교반을 시키면서 메틸마그네슘브로마이드(0.5ml, 10N 에테르용액)을 방울방울 더한 다음, 상온에서 30분간 교반시켜 준 뒤에, 반응 온도를 40∼50℃까지 올려 환류시키면서 1시간 더 반응을 시킨다. 이 반응 용액을 냉각시키면서, 10ml의 물을 적가한다. 이를 에테르로 추출한 후에, 묽은 염산으로 씻은 후, 함염수로 씻고, 무수 황산마그네슘으로 건조한 후에, 감압 증발시켰다. 이를 컬럼 크로마토그래피하여 정제한다. (실리카겔, 70∼200메쉬, 헥산 : 에틸 아세테이트 = 4 : 1)Methyl magnesium bromide (0.5ml, 10N ether solution) was added dropwise to the ether solution of the starting material aldehyde (0.76g), followed by stirring at room temperature for 30 minutes, and then the reaction temperature was raised to 40-50 ° C. The reaction is further performed for 1 hour while refluxing. 10 ml of water is added dropwise while cooling the reaction solution. After extraction with ether, washed with dilute hydrochloric acid, washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. It is purified by column chromatography. (Silica gel, 70-200 mesh, hexane: ethyl acetate = 4: 1)

NMR(H, 60MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.30(m,singlets at 0.67, 0.73, 0.90, 1.25, 1.40), 3.40∼4.40(m,7H)NMR (H, 60 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.30 (m, singlets at 0.67, 0.73, 0.90, 1.25, 1.40), 3.40 to 4.40 (m, 7H)

; 3540(m), 2950(s), 2890(s), 1470(m), 1385(m), 1340(w), 1305(w), 1290(m), 1230(m), 1215(m), 1190(m), 1165(m), 1130(m), 1080(s), 1055(s), 1040(s), 1000(w), 970(m), 950(m), 905(w), 880(w), 855(w), 825(w).

; 3540 (m), 2950 (s), 2890 (s), 1470 (m), 1385 (m), 1340 (w), 1305 (w), 1290 (m), 1230 (m), 1215 (m), 1190 (m), 1165 (m), 1130 (m), 1080 (s), 1055 (s), 1040 (s), 1000 (w), 970 (m), 950 (m), 905 (w), 880 (w), 855 (w), 825 (w).

위의 화합물 0.5g을 테트라히드로푸란(20ml)에 녹인 후에 6N염산용액(5ml)을 더한 다음 상온에서 밤새도록 교반시켜 준다. 감압하에서 용매를 제거한 후, 잔사를 컬럼 크로마토그래피하여 정제한다. 최종 물질을 얻고, 이를 헥산 에테르 용매 혼합물(실리카겔, 클로로포폼 : 메탄올=40 : 1) 잘 처리하여 고상의 분말을 얻는다.0.5 g of the above compound was dissolved in tetrahydrofuran (20 ml), 6N hydrochloric acid solution (5 ml) was added, and the mixture was stirred overnight at room temperature. After removing the solvent under reduced pressure, the residue is purified by column chromatography. Obtain the final material and treat it well with hexane ether solvent mixture (silica gel, chlorophosphate: methanol = 40: 1) to obtain a solid powder.

융점 : 236∼241℃Melting Point: 236 ~ 241 ℃

수율 : 79.2%Yield: 79.2%

원소분석(C₂₄H₄₀O₄)Elemental Analysis (C ₂₄ H ₄₀ O ₄ )

계산치(%) : C; 73.49, H; 10.20, O; 16.31Calculated (%): C; 73.49, H; 10.20, O; 16.31

실측치(%) : C; 73.34, H; 10.12, O; 15.94Found (%): C; 73.34, H; 10.12, O; 15.94

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.6∼2.25(m,singlets at 0.67, 0.75, 0.9, 1.55), 2.52∼2.80(1H, m), 3.35∼4.10(3H, m)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.6 to 2.25 (m, singlets at 0.67, 0.75, 0.9, 1.55), 2.52 to 2.80 (1H, m), 3.35 to 4.10 (3H, m)

; 3400(s), 2950(s), 2875(m), 1725(s), 1470(m), 1450(m), 1430(m), 1385(m), 1350(w), 1340(w), 1325(w), 1310(w), 1280(w), 1260(w), 1230(w), 1200(w), 1160(w), 1130(w), 1115(w), 1100(m), 1075(m), 1035(m), 1005(m), 985(w), 965(m), 940(w), 920(w), 860(w), 705(w), 680(w), 640(w), 580(w).

; 3400 (s), 2950 (s), 2875 (m), 1725 (s), 1470 (m), 1450 (m), 1430 (m), 1385 (m), 1350 (w), 1340 (w), 1325 (w), 1310 (w), 1280 (w), 1260 (w), 1230 (w), 1200 (w), 1160 (w), 1130 (w), 1115 (w), 1100 (m), 1075 (m), 1035 (m), 1005 (m), 985 (w), 965 (m), 940 (w), 920 (w), 860 (w), 705 (w), 680 (w), 640 (w), 580 (w).

[실시예 11]Example 11

2α,3α-디히드록시-20-(1-히드록시부틸)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxybutyl) -5α-pregnan-6-one

실시예 9에서와 동일한 방법으로 제조하였다. 중간체인 6,6-에틸렌디옥시-2α,3α-이소프로필리덴-디옥시-20-[(1-히드록시부틸)]-5α-프레그난-6-온의 스펙트럼 데이타는 하기와 같다.Prepared in the same manner as in Example 9. The spectral data of the intermediate 6,6-ethylenedioxy-2α, 3α-isopropylidene-dioxy-20-[(1-hydroxybutyl)]-5α-pregnan-6-one are as follows.

융점 : 85∼88℃Melting Point: 85 ~ 88 ℃

수율 : 75.4%Yield: 75.4%

NMRδ(60MHz, CDCl₃/TMS) : 0.55∼2.30(m,singlets at 0.60, 0.75, 0.87, 1.03, 1.17, 1.21, 1.33, 1.60), 3.50∼4.30(m,7H).NMRδ (60 MHz, CDCl ₃ / TMS): 0.55 to 2.30 (m, singlets at 0.60, 0.75, 0.87, 1.03, 1.17, 1.21, 1.33, 1.60), 3.50 to 4.30 (m, 7H).

IRνmax(cm^-1); 3540(m), 2950(s), 2890(s), 1470(m), 1385(m), 1340(m), 1305(m), 1290(m), 1230(m), 1115(m), 1190(m), 1165(m), 1130(m), 1080(s), 1055(s), 1040(s), 1000(m), 970(m), 945(m), 920(w), 910(w), 880(w), 855(w), 825(w), 790(w), 770(w), 730(w), 705(w), 690(w), 660(w), 640(w).IRv max (cm ^-1 ); 3540 (m), 2950 (s), 2890 (s), 1470 (m), 1385 (m), 1340 (m), 1305 (m), 1290 (m), 1230 (m), 1115 (m), 1190 (m), 1165 (m), 1130 (m), 1080 (s), 1055 (s), 1040 (s), 1000 (m), 970 (m), 945 (m), 920 (w), 910 (w), 880 (w), 855 (w), 825 (w), 790 (w), 770 (w), 730 (w), 705 (w), 690 (w), 660 (w), 640 (w).

위 중간체를 실시예 9의 후반부의 방법과 동일하게 조작하여 표제의 최종 화합물의 데이터는 아래와 같다.The above intermediate was operated in the same manner as in the latter part of Example 9, whereby the data of the title compound was as follows.

융점 : 232∼234℃Melting Point: 232 ~ 234 ℃

수율 : 74.5%Yield: 74.5%

원소분석(C₂₅H₄₂O₄)Elemental Analysis (C ₂₅ H ₄₂ O ₄ )

계산치(%) : C; 73.91, H; 10.34, O; 15.75Calculated (%): C; 73.91, H; 10.34, O; 15.75

실측치(%) : C; 73.27, H; 10.84, O; 15.42Found (%): C; 73.27, H; 10.84, 0; 15.42

NMRδ(H, 80MHz, CDCI₃/TMS) : 0.6∼2.30(m, singlets at 0.67, 0.80, 0.92, 1.37, 1.70), 2.50∼2.80(1H, m), 3.50∼4.10(3H, m).NMRδ (H, 80 MHz, CDCI ₃ / TMS): 0.6 to 2.30 (m, singlets at 0.67, 0.80, 0.92, 1.37, 1.70), 2.50 to 2.80 (1H, m), 3.50 to 4.10 (3H, m).

; 3420(s), 2960(s), 2880(s), 1725(s), 1475(m), 1470(m), 1465(m), 1430(m), 1420(m), 1390(m), 1330(m), 1315(m), 1275(m), 1200(w), 1160(w), 1140(w), 1115(w), 1100(m), 1075(m), 1035(m), 1005(m), 965(m), 935(m), 925(w), 865(w), 820(w), 730(w), 705(w), 680(w), 640(w), 595(w), 465(w), 420(w).

; 3420 (s), 2960 (s), 2880 (s), 1725 (s), 1475 (m), 1470 (m), 1465 (m), 1430 (m), 1420 (m), 1390 (m), 1330 (m), 1315 (m), 1275 (m), 1200 (w), 1160 (w), 1140 (w), 1115 (w), 1100 (m), 1075 (m), 1035 (m), 1005 (m), 965 (m), 935 (m), 925 (w), 865 (w), 820 (w), 730 (w), 705 (w), 680 (w), 640 (w), 595 (w), 465 (w), 420 (w).

[실시예 12]Example 12

2α,3α-디히드록시-20-(1-히드록시아밀)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxyamyl) -5α-pregnan-6-one

상기 일반식(II)의 화합물(0.76gr)과 n-부틸마그네슘브로마이드로부터 실시예 9의 방법과 동일한 방법으로 제조하였다. 중간체인 6,6-에틸렌디옥시-2α,3α-이소프로필리덴디옥시-20-[(1-히드록시부틸)]-5α-프레그난의 스펙트럼 데이터는 하기와 같다.It was prepared in the same manner as in Example 9 from compound (0.76 gr) and n-butyl magnesium bromide of formula (II). The spectral data of the intermediate 6,6-ethylenedioxy-2α, 3α-isopropylidenedioxy-20-[(1-hydroxybutyl)]-5α-pregnan are as follows.

융점 : 70∼73℃Melting Point: 70 ~ 73 ℃

수율 : 69.7%Yield: 69.7%

; 3430(m), 2900(s), 2830(s), 1460(m), 1440(m), 1380(m), 1375(m), 1335(w), 1305(w), 1290(w), 1260(w), 1230(m), 1210(m), 1200(m), 1170(m), 1140(m), 1130(w), 1090(m), 1070(s), 1050(m), 980(m), 960(m), 950(w), 930(w), 920(w), 900(w), 870(w).

; 3430 (m), 2900 (s), 2830 (s), 1460 (m), 1440 (m), 1380 (m), 1375 (m), 1335 (w), 1305 (w), 1290 (w), 1260 (w), 1230 (m), 1210 (m), 1200 (m), 1170 (m), 1140 (m), 1130 (w), 1090 (m), 1070 (s), 1050 (m), 980 (m), 960 (m), 950 (w), 930 (w), 920 (w), 900 (w), 870 (w).

NMR δ(60MHz, CDCl₃/TMS) : 0.60∼2.5(m,singlets at 0.66, 0.68, 0.87, 1.17, 1.27, 1.34, 1.56), 3.5∼4.4(m,7H).NMR δ (60 MHz, CDCl ₃ / TMS): 0.60 to 2.5 (m, singlets at 0.66, 0.68, 0.87, 1.17, 1.27, 1.34, 1.56), 3.5 to 4.4 (m, 7H).

또한 표제의 최종 물질의 데이터는 하기와 같다.In addition, the data of the final material of the title is as follows.

융점 : 185.5∼186.5℃Melting Point: 185.5 ~ 186.5 ℃

수율 :68.3%Yield: 68.3%

IR(KBr-pellet)νmax(cm^-1) : 3420(s), 2955(s), 2860(s), 1720(s), 1470(w), 1460(w), 1450(w), 1435(w), 1420(w), 1385(m), 1335(m), 1310(w), 1280(m), 1260(m), 1210(w), 1155(w), 1130(w), 1120(w), 1100(w), 1075(m), 1035(s), 1005(m), 990(m), 970(m), 930(w), 920(w), 860(w), 850(w), 795(w), 705(w), 680(w), 640(w), 595(w).IR (KBr-pellet) ν max (cm ^-1 ): 3420 (s), 2955 (s), 2860 (s), 1720 (s), 1470 (w), 1460 (w), 1450 (w), 1435 ( w), 1420 (w), 1385 (m), 1335 (m), 1310 (w), 1280 (m), 1260 (m), 1210 (w), 1155 (w), 1130 (w), 1120 ( w), 1100 (w), 1075 (m), 1035 (s), 1005 (m), 990 (m), 970 (m), 930 (w), 920 (w), 860 (w), 850 ( w), 795 (w), 705 (w), 680 (w), 640 (w), 595 (w).

NMRδ(H, 80MHz, CDCl₃/TMS) : 0.60∼2.40(m,singlets at 0.68, 0.75, 0.90, 1.35), 2.50∼2.80(1H, m), 3.50∼4.15(2H, m).NMRδ (H, 80 MHz, CDCl ₃ / TMS): 0.60 to 2.40 (m, singlets at 0.68, 0.75, 0.90, 1.35), 2.50 to 2.80 (1H, m), 3.50 to 4.15 (2H, m).

원소분석(C₂₆H₄₄O₄)Elemental Analysis (C ₂₆ H ₄₄ O ₄ )

계산치(%) : C; 74.31, H; 10.47, O; 15.22Calculated (%): C; 74.31, H; 10.47, O; 15.22

실측치(%) : C; 73.84, H; 10.37, O; 15.42Found (%): C; 73.84, H; 10.37, O; 15.42

[실시예 13]Example 13

2α,3α-디히드록시 - 20-(1-히드록시헥실)-5α-프레그난-6-온2α, 3α-dihydroxy-20- (1-hydroxyhexyl) -5α-pregnan-6-one

일반식(II) 화합물(0.76g)와 n-아밀 마그네슘 브로마이드로부터, 실시예 9와 동일한 방법으로 제조하였다. 중간체인 6,6-에틸렌디옥시-2α,3α-이소프로필리덴-디옥시-20-(1-히드록시헥실)-5α-프레그난-6-온의 스펙트럼 데이터는 아래와 같다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and n-amyl magnesium bromide. Spectral data of the intermediate 6,6-ethylenedioxy-2α, 3α-isopropylidene-dioxy-20- (1-hydroxyhexyl) -5α-pregnan-6-one are shown below.

융점 : 125∼128℃Melting Point: 125 ~ 128 ℃

수율 : 77.5%Yield: 77.5%

; 3520(m), 2950(s), 2880(s), 1470(m), 1380(m), 1340(w), 1305(w), 1290(m), 1230(m), 1215(m), 1195(m), 1165(m), 1140(m), 1080(s), 1055(s), 1040(s), 970(m), 950(m), 935(m), 915(w), 905(w), 875(w), 855(w), 825(w), 790(w), 770(w), 725(w), 710(w), 690(w), 595(w), 570(w), 510(w), 500(w), 450(w).

; 3520 (m), 2950 (s), 2880 (s), 1470 (m), 1380 (m), 1340 (w), 1305 (w), 1290 (m), 1230 (m), 1215 (m), 1195 (m), 1165 (m), 1140 (m), 1080 (s), 1055 (s), 1040 (s), 970 (m), 950 (m), 935 (m), 915 (w), 905 (w), 875 (w), 855 (w), 825 (w), 790 (w), 770 (w), 725 (w), 710 (w), 690 (w), 595 (w), 570 (w), 510 (w), 500 (w), 450 (w).

NMR(H, 60MHz, CDCl₃/TMS)δ(ppm) : 0.5∼2.3(m,singlets at 0.57, 0.72, 0.80, 1.24, 1.29, 1.55) 3.30∼4.40(m,7H)NMR (H, 60 MHz, CDCl ₃ / TMS) δ (ppm): 0.5 to 2.3 (m, singlets at 0.57, 0.72, 0.80, 1.24, 1.29, 1.55) 3.30 to 4.40 (m, 7H)

보호기를 제거한 표제화합물의 데이터는 다음과 같다.The data of the title compound without protecting group are as follows.

융점 : 189.5∼190℃Melting Point: 189.5 ~ 190 ℃

수율 : 81.0%Yield: 81.0%

NMRδ(H, 80MHz, CDCl₃/TMS) : 0.60∼2.40(m,singlets at 0.65, 0.73, 1.30, 1.57) 2.50∼2.75(1H, m), 3.50∼4.10(3H, m).NMRδ (H, 80 MHz, CDCl ₃ / TMS): 0.60 to 2.40 (m, singlets at 0.65, 0.73, 1.30, 1.57) 2.50 to 2.75 (1H, m), 3.50 to 4.10 (3H, m).

IRνmaxKBr(cm^-1); 3450(s), 2960(s), 2870(s), 1727(s), 1470(m), 1450(m), 1415(m), 1385(m), 1340(w), 1330(w), 1310(w), 1275(m), 1230(m), 1195(m), 1160(w), 1140(w), 1100(m), 1080(m), 1055(m), 1040(m), 1005(m), 980(m), 920(m), 860(w), 815(w), 745(w), 705(w), 680(w), 645(w), 590(w), 465(w).IRv max KBr (cm ^-1 ); 3450 (s), 2960 (s), 2870 (s), 1727 (s), 1470 (m), 1450 (m), 1415 (m), 1385 (m), 1340 (w), 1330 (w), 1310 (w), 1275 (m), 1230 (m), 1195 (m), 1160 (w), 1140 (w), 1100 (m), 1080 (m), 1055 (m), 1040 (m), 1005 (m), 980 (m), 920 (m), 860 (w), 815 (w), 745 (w), 705 (w), 680 (w), 645 (w), 590 (w), 465 (w).

원소분석(C₂₇H₄₆O)Elemental Analysis (C ₂₇ H ₄₆ O)

계산치(%) : C; 74.68, H; 10.59, O; 14.73Calculated (%): C; 74.68, H; 10.59, O; 14.73

실측치(%) : C; 74.23, H; 10.43, O; 14.83Found (%): C; 74.23, H; 10.43, O; 14.83

[실시예 14]Example 14

2α,3α-디히드록시-20-(1-히드록시헵틸)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxyheptyl) -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 n-헥실마그네슘브로마이드를 사용하여 실시예 9와 동일한 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 9 using compound (0.76 g) and n-hexyl magnesium bromide.

중간체인 6,6-에틸렌디옥시-2α,3α-이소프로필렌리덴-디옥시-20-(1-히드록시에틸)-5α-프레그난-6-온의 스펙트럼 데이터는 다음과 같다.The spectral data of the intermediate 6,6-ethylenedioxy-2α, 3α-isopropyleneidene-dioxy-20- (1-hydroxyethyl) -5α-pregnan-6-one are as follows.

융점 : 156∼159℃Melting Point: 156 ~ 159 ℃

수율 : 74.2%Yield: 74.2%

IRνmaxKBr(cm^-1) : 3550(m), 2950(s), 2880(s), 1470(m), 1380(m), 1335(m), 1305(m), 1290(m), 1240(m), 1230(m), 1220(m), 1190(m), 1165(m), 1145(m), 1140(m), 1120(m), 1080(s), 1055(s), 1045(s), 1015(m), 1000(m), 970(m), 945(m), 905(w), 850(w), 825(w), 790(w), 770(w), 760(w), 725(w), 705(w), 690(w), 660(w), 645(w), 590(w), 570(w), 505(w), 495(w).IRν max KBr (cm ^-1 ): 3550 (m), 2950 (s), 2880 (s), 1470 (m), 1380 (m), 1335 (m), 1305 (m), 1290 (m), 1240 (m ), 1230 (m), 1220 (m), 1190 (m), 1165 (m), 1145 (m), 1140 (m), 1120 (m), 1080 (s), 1055 (s), 1045 (s ), 1015 (m), 1000 (m), 970 (m), 945 (m), 905 (w), 850 (w), 825 (w), 790 (w), 770 (w), 760 (w ), 725 (w), 705 (w), 690 (w), 660 (w), 645 (w), 590 (w), 570 (w), 505 (w), 495 (w).

NMR δ(60MHz, CDCl₃/TMS) : 0.50∼2.40(m,singlets at 0.68, 0.83, 0.89, 0.99, 1.13, 1.34, 1.41), 3.40∼4.50(m,7H)NMR δ (60 MHz, CDCl ₃ / TMS): 0.50 to 2.40 (m, singlets at 0.68, 0.83, 0.89, 0.99, 1.13, 1.34, 1.41), 3.40 to 4.50 (m, 7H)

상기 중간물질의 보호기를 제거하여 얻은 표제의 최종화합물의 데이터는 아래와 같다.The data of the final compound of the title obtained by removing the protecting group of the intermediate is as follows.

융점 : 191.5∼193.5℃Melting Point: 191.5 ~ 193.5 ℃

수율 : 83.2%Yield: 83.2%

; 3450(s), 2950(s), 2870(s), 1725(s), 1470(m), 1455(m), 1430(w), 1415(m), 1385(m), 1340(w), 1330(w), 1310(w), 1275(m), 1265(m), 1220(m), 1195(m), 1160(w), 1140(w), 1100(m), 1080(m), 1050(m), 1040(m), 1010(m), 980(m), 965(w), 950(w), 940(w), 920(w), 860(w), 705(w), 680(w), 645(w), 590(w), 555(w), 540(w), 445(w).

; 3450 (s), 2950 (s), 2870 (s), 1725 (s), 1470 (m), 1455 (m), 1430 (w), 1415 (m), 1385 (m), 1340 (w), 1330 (w), 1310 (w), 1275 (m), 1265 (m), 1220 (m), 1195 (m), 1160 (w), 1140 (w), 1100 (m), 1080 (m), 1050 (m), 1040 (m), 1010 (m), 980 (m), 965 (w), 950 (w), 940 (w), 920 (w), 860 (w), 705 (w), 680 (w), 645 (w), 590 (w), 555 (w), 540 (w), 445 (w).

NMRδ(H, 80MHz, CDCl₃/TMS) : 0.6∼2.40(m, singlets at 0.68, 0.80, 0.88, 0.93, 1.30)NMRδ (H, 80 MHz, CDCl ₃ / TMS): 0.6 to 2.40 (m, singlets at 0.68, 0.80, 0.88, 0.93, 1.30)

2.55∼2.80(1H, m).2.55 to 2.80 (1 H, m).

3.50∼4.10(3H, m).3.50 to 4.10 (3H, m).

원소분석(C₂₈H₄₈O₄)Elemental Analysis (C ₂₈ H ₄₈ O ₄ )

계산치(%) : C; 75.02, H; 10.71, O; 14.27Calculated (%): C; 75.02, H; 10.71, O; 14.27

실측치(%) : C; 74.23, H; 10.98, O; 14.48Found (%): C; 74.23, H; 10.98, O; 14.48

[실시예 15]Example 15

2α,3α-디히드록시-20-(1-히드록시옥틸)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxyoctyl) -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 n-헵틸마스네슘브로마이드를 사용하여 실시예 9의 방법과 동일하게 조작하여 제조하였다. 중간체인 6,6-에틸렌디옥시-2α,3α-이소프로필렌리덴-디옥시-20-(1-히드록시에틸)-5α-프레그난의 스펙트럼 데이터는 다음과 같다.Compound (II) was prepared by the same procedure as in Example 9 using compound (0.76 g) and n-heptyl magnesium bromide. Spectral data of the intermediate 6,6-ethylenedioxy-2α, 3α-isopropyleneidene-dioxy-20- (1-hydroxyethyl) -5α-pregnan are as follows.

수율 : 78%Yield: 78%

; 3540(m), 2950(s), 2880(s), 1470(m), 1385(m), 1340(w), 1305(w), 1290(m), 1230(m), 1220(m), 1195(m), 1165(m), 1140(m), 1130(m), 1080(s), 1055(s), 1040(s), 1000(m), 970(m), 950(m), 910(w), 880(w), 850(w), 830(w), 790(w), 725(w), 705(w), 695(w), 660(w), 640(w), 590(w), 570(w), 505(w), 500(w)

; 3540 (m), 2950 (s), 2880 (s), 1470 (m), 1385 (m), 1340 (w), 1305 (w), 1290 (m), 1230 (m), 1220 (m), 1195 (m), 1165 (m), 1140 (m), 1130 (m), 1080 (s), 1055 (s), 1040 (s), 1000 (m), 970 (m), 950 (m), 910 (w), 880 (w), 850 (w), 830 (w), 790 (w), 725 (w), 705 (w), 695 (w), 660 (w), 640 (w), 590 (w), 570 (w), 505 (w), 500 (w)

NMRδ(60MHz, CDCl₃/TMS) : 0.50∼2.40m(singlets at 0.58, 0.70, 0.77, 1.20). 3.3∼4.40(m,7H).NMRδ (60 MHz, CDCl ₃ / TMS): 0.50 to 2.40 m (singlets at 0.58, 0.70, 0.77, 1.20). 3.3 to 4.40 (m, 7H).

상기 중간 화합물의 보호기를 제거하여 표제의 최종 물질을 얻었다.The protecting group of the intermediate compound was removed to give the title final material.

융점 : 169∼171.5℃Melting Point: 169 ~ 171.5 ℃

수율 : 74.4%Yield: 74.4%

; 3450(s), 2950(s), 2870(s), 1725(s), 1470(m), 1450(m), 1430(m), 1420(m), 1385(m), 1340(w), 1327(w), 1312(m), 1275(m), 1230(m), 1195(m), 1160(w), 1100(w), 1075(m), 1050(m), 1045(m), 1030(m), 985(w), 960(m), 935(w), 920(w), 860(W), 705(w), 680(w), 645(w), 590(w), 445(w), 400(w).

; 3450 (s), 2950 (s), 2870 (s), 1725 (s), 1470 (m), 1450 (m), 1430 (m), 1420 (m), 1385 (m), 1340 (w), 1327 (w), 1312 (m), 1275 (m), 1230 (m), 1195 (m), 1160 (w), 1100 (w), 1075 (m), 1050 (m), 1045 (m), 1030 (m), 985 (w), 960 (m), 935 (w), 920 (w), 860 (W), 705 (w), 680 (w), 645 (w), 590 (w), 445 (w), 400 (w).

NMRδ(H, 80MHz, CDCl₃/TMS) : 0.60∼2.40(m,singlets at 0.65, 0.74, 0.85, 0.90, 1.25) 2.45∼2.75(1H, m)NMRδ (H, 80 MHz, CDCl ₃ / TMS): 0.60 to 2.40 (m, singlets at 0.65, 0.74, 0.85, 0.90, 1.25) 2.45 to 2.75 (1H, m)

3.45∼4.10(3H, m).3.45 to 4.10 (3H, m).

원소분석(C₂₉H₅₀O₄)Elemental Analysis (C ₂₉ H ₅₀ O ₄ )

계산치(%) : C; 75.35, H; 10.82, O; 13.84Calculated (%): C; 75.35, H; 10.82, O; 13.84

실측치(%) : C; 75.71, H; 10.92, O; 13.43Found (%): C; 75.71, H; 10.92, O; 13.43

[실시예 16]Example 16

2α,3α-디히드록시-20-(1-히드록시노난닐)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxynonanyl) -5α-pregnan-6-one

일반식(II) 화합물(0.76gr)과 n-옥틸마그네슘브로마이드로부터 실시예 9의 방법에 따라 제조했다. 중간물질인 6,6-에틸렌디옥시-2α,3α-이소프로필렌리덴-디옥시-(1-히드록시노난일)-5α-프레그난의 스펙트럼 데이터는 다음과 같다.Prepared according to the method of Example 9 from general formula (II) compound (0.76 gr) and n-octyl magnesium bromide. Spectral data of the intermediate 6,6-ethylenedioxy-2α, 3α-isopropyleneidene-dioxy- (1-hydroxynonanyl) -5α-pregnan are as follows.

수율 : 77.2%Yield: 77.2%

; 3400(m), 2900(s), 2850(s), 1470(m), 1390(m), 1340(m), 1310(w), 1300(w), 1240(w), 1215(w), 1205(m), 1190(m), 1160(w), 1150(w), 1100(m), 1080(s), 1060(m), 1000(w), 980(w), 950(w), 940(w), 910(w), 880(w).

; 3400 (m), 2900 (s), 2850 (s), 1470 (m), 1390 (m), 1340 (m), 1310 (w), 1300 (w), 1240 (w), 1215 (w), 1205 (m), 1190 (m), 1160 (w), 1150 (w), 1100 (m), 1080 (s), 1060 (m), 1000 (w), 980 (w), 950 (w), 940 (w), 910 (w), 880 (w).

NMRδ(60MHz, CDCl₃/TMS) : 0.60∼2.40(m, singlets at 0.66, 0.77, 0.84, 1.25, 1.65), 3.40∼4.40(m,7H)NMRδ (60 MHz, CDCl ₃ / TMS): 0.60 to 2.40 (m, singlets at 0.66, 0.77, 0.84, 1.25, 1.65), 3.40 to 4.40 (m, 7H)

상기 중간물질의 보호기를 제거하여 얻은 표제화합물의 데이터는 다음과 같다.The data of the title compound obtained by removing the protecting group of the intermediate is as follows.

융점 : 161~163℃ 수율 : 639%Melting Point: 161 ~ 163 ℃ Yield: 639%

; 3440(s), 2950(s), 2870(s), 1725(s), 1470(m), 1425(m), 1370(m), 1340(w), 1325(w), 1320(w), 1275(w), 1225(w), 1195(w), 1115(w), 1100(w), 1075(m), 1050(m), 1040(m), 1030(m), 1020(m), 985(w), 960(m), 935(w), 920(w), 860(w), 705(w), 645(w), 595(w), 550(W), 445(w)

; 3440 (s), 2950 (s), 2870 (s), 1725 (s), 1470 (m), 1425 (m), 1370 (m), 1340 (w), 1325 (w), 1320 (w), 1275 (w), 1225 (w), 1195 (w), 1115 (w), 1100 (w), 1075 (m), 1050 (m), 1040 (m), 1030 (m), 1020 (m), 985 (w), 960 (m), 935 (w), 920 (w), 860 (w), 705 (w), 645 (w), 595 (w), 550 (W), 445 (w)

NMRδ(80MHz, CDCl₃/TMS) : 0.55∼2.45(m,singlets at 0.67, 0.75, 0.87, 0.93, 1.27, 1.65, 1.83), 2.55∼2.80(1H, m), 3.50∼4.10(3H, m)NMRδ (80 MHz, CDCl ₃ / TMS): 0.55 to 2.45 (m, singlets at 0.67, 0.75, 0.87, 0.93, 1.27, 1.65, 1.83), 2.55 to 2.80 (1H, m), 3.50 to 4.10 (3H, m)

원소분석(C₃₀H₅₂O₄)Elemental Analysis (C ₃₀ H ₅₂ O ₄ )

계산치(%) : C; 75.65, H; 10.92, O; 13.43Calculated (%): C; 75.65, H; 10.92, O; 13.43

실측치(%) : C; 75.32, H; 10.84, O; 13.41Found (%): C; 75.32, H; 10.84, 0; 13.41

[실시예 17]Example 17

2α,3α-디히드록시-20-{(1-히드록시-1-이소아밀)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-1-isoamyl) methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 이소아밀마그네슘브로마이드로부터 실시예 9의 방법과 동일하게 제조하였다. 스펙트럼 데이터는 다음과 같다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and isoamyl magnesium bromide. The spectral data are as follows.

융점 : 182∼186℃Melting Point: 182 ~ 186 ℃

; 3450(s), 2955(s), 2860(s), 1720(s), 1460(w), 1450(w), 1435(w), 1420(w), 1385(m), 1335(m), 1310(w), 1280(m), 1260(m), 1210(w), 1155(w), 1130(w), 1120(w), 1100(w), 1075(m), 1035(s), 1005(m), 990(m), 970(m), 930(w), 920(w), 866(w), 850(w), 795(w), 705(w), 680(w), 640(w).

; 3450 (s), 2955 (s), 2860 (s), 1720 (s), 1460 (w), 1450 (w), 1435 (w), 1420 (w), 1385 (m), 1335 (m), 1310 (w), 1280 (m), 1260 (m), 1210 (w), 1155 (w), 1130 (w), 1120 (w), 1100 (w), 1075 (m), 1035 (s), 1005 (m), 990 (m), 970 (m), 930 (w), 920 (w), 866 (w), 850 (w), 795 (w), 705 (w), 680 (w), 640 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.40(m,singlets at 0.68, 0.75), 2.50∼2.80(1H, m). 3.50∼4.15(3H, m)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.40 (m, singlets at 0.68, 0.75), 2.50 to 2.80 (1H, m). 3.50 to 4.15 (3H, m)

원소분석(C₂₇H₄₆O₄)Elemental Analysis (C ₂₇ H ₄₆ O ₄ )

계산치(%) : C : 74.68, H : 10.59, O : 14.73Calculated Value (%): C: 74.68, H: 10.59, O: 14.73

실측치(%) : C : 75.02, H : 10.43, O : 13.92Found (%): C: 75.02, H: 10.43, O: 13.92

[실시예 18]Example 18

2α,3α-디히드록시-20-{(1-히드록시-1-이소헵틸)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-1-isoheptyl) methyl} -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 이소헵틸마그네슘브로마이드로부터 실시예 9의 방법과 동일하게 제조하였다. 그의 데이터는 아래와 같다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and isoheptyl magnesium bromide. His data is shown below.

융점 : 189∼193℃Melting Point: 189 ~ 193 ℃

; 3440(s), 2950(s), 2865(s), 1720(s), 1460(w), 1450(s), 1435(w), 1420(w), 1385(m), 1335(m), 1310(w), 1280(m), 1260(m), 1210(w), 1155(w), 1130(w), 1120(w), 1110(w), 1075(m), 1035(w), 1010(m), 990(m), 970(m), 930(w), 920(w), 860(w), 845(w), 795(w), 710(w), 680(w).

; 3440 (s), 2950 (s), 2865 (s), 1720 (s), 1460 (w), 1450 (s), 1435 (w), 1420 (w), 1385 (m), 1335 (m), 1310 (w), 1280 (m), 1260 (m), 1210 (w), 1155 (w), 1130 (w), 1120 (w), 1110 (w), 1075 (m), 1035 (w), 1010 (m), 990 (m), 970 (m), 930 (w), 920 (w), 860 (w), 845 (w), 795 (w), 710 (w), 680 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.40(m, singlets at 0.68, 0.75, 0.83, 0.94), 2.50∼2.80(1H, m), 3.45∼4.10(3H, m)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.40 (m, singlets at 0.68, 0.75, 0.83, 0.94), 2.50 to 2.80 (1H, m), 3.45 to 4.10 (3H, m)

원소분석(C₂₉H₅₀O₄)Elemental Analysis (C ₂₉ H ₅₀ O ₄ )

실측치(%) : C; 74.29, H; 10.21, O; 13.46Found (%): C; 74.29, H; 10.21, O; 13.46

[실시예 19]Example 19

2α,3α-디히드록시-20-{(1-히드록시-1-sec-부틸)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-1-sec-butyl) methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76gr)과 sec-부틸마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from Compound (II) (0.76 gr) and sec-butylmagnesium bromide.

융점 : 192∼196℃Melting Point: 192∼196 ℃

; 3460(s), 2950(s), 2855(s), 1720(s), 1460(w), 1450(w), 1430(w), 1420(w), 1385(m), 1335(m), 1320(w), 1310(w), 1275(m), 1260(m), 1210(m), 1155(w), 1130(w), 1120(w), 1110(w), 1095(m), 1040(s), 1015(m), 990(m), 970(m), 930(w), 920(w), 860(w), 845(w), 780(w), 720(w).

; 3460 (s), 2950 (s), 2855 (s), 1720 (s), 1460 (w), 1450 (w), 1430 (w), 1420 (w), 1385 (m), 1335 (m), 1320 (w), 1310 (w), 1275 (m), 1260 (m), 1210 (m), 1155 (w), 1130 (w), 1120 (w), 1110 (w), 1095 (m), 1040 (s), 1015 (m), 990 (m), 970 (m), 930 (w), 920 (w), 860 (w), 845 (w), 780 (w), 720 (w).

NMR(H, 80MHz, CDCl₃/TMS) : δ(ppm) : 0.60∼2.45(m, singlets at 0.67, 0.74, 0.85, 0.97), 2.50∼2.78(1H, m), 3.45∼4.15(3H, m)NMR (H, 80 MHz, CDCl ₃ / TMS): δ (ppm): 0.60 to 2.45 (m, singlets at 0.67, 0.74, 0.85, 0.97), 2.50 to 2.78 (1H, m), 3.45 to 4.15 (3H, m )

원소분석(C₂₆H₄₄O₄)Elemental Analysis (C ₂₆ H ₄₄ O ₄ )

실측치(%) : C; 72.92, H; 10.27, O; 14.83Found (%): C; 72.92, H; 10.27, O; 14.83

[실시예 20]Example 20

2α,3α-디히드록시-20-{[1-히드록시-1-(2-메틸부틸)]메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{[1-hydroxy-1- (2-methylbutyl)] methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 sec-아밀마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and sec-amyl magnesium bromide.

융점 : 202∼204℃Melting Point: 202 ~ 204 ℃

: 3450(s), 2950(s), 2855(s), 1725(s), 1455(w), 1430(w), 1420(w), 1385(m), 1325(w), 1315(w), 1280(m), 1270(m), 1210(w), 1166(w), 1140(w), 1120(w), 1100(w), 1080(m), 1040(s), 1015(m), 985(m), 980(m), 930(w), 920(w), 860(w), 845(w), 780(w), 720(w), 630(w)

: 3450 (s), 2950 (s), 2855 (s), 1725 (s), 1455 (w), 1430 (w), 1420 (w), 1385 (m), 1325 (w), 1315 (w) , 1280 (m), 1270 (m), 1210 (w), 1166 (w), 1140 (w), 1120 (w), 1100 (w), 1080 (m), 1040 (s), 1015 (m) , 985 (m), 980 (m), 930 (w), 920 (w), 860 (w), 845 (w), 780 (w), 720 (w), 630 (w)

NMR(H, 80MHz, CDCl₃/TMS);δ(ppm) : 0.60∼2.45(m,singlets at 0.67, 0.74, 0.80, 0.94), 2.50∼2.80(1H, m), 3.45∼4.15(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS); δ (ppm): 0.60 to 2.45 (m, singlets at 0.67, 0.74, 0.80, 0.94), 2.50 to 2.80 (1H, m), 3.45 to 4.15 (3H, m ).

원소분석 : C₂₇H₄₆O₄ Elemental Analysis: C ₂₇ H ₄₆ O ₄

실측치(%) : C; 75.72, H; 10.92, O; 13.84Found (%): C; 75.72, H; 10.92, O; 13.84

[실시예 21]Example 21

2α,3α-디히드록시-20-[(1-히드록시-1-(2-메틸-3-메틸부틸)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1- (2-methyl-3-methylbutyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 2-메틸이소아밀마그네슘 브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.A compound of the formula (II) (0.76 g) and 2-methylisoamyl magnesium bromide were prepared in the same manner as in Example 9.

융점 : 194∼198.5℃Melting Point: 194 ~ 198.5 ℃

; 3440(s), 2950(s), 2865(s), 1720(s), 1460(w), 1450(w), 1430(w), 1420(w), 1385(m), 1335(m), 1310(w), 1280(m), 1260(m), 1210(w), 1155(w), 1130(w), 1120(w), 1100(w), 1075(m), 1035(s), 1010(m), 990(m), 970(m), 930(w), 920(w), 860(W), 840(W), 795(w), 710(w), 680(w).

; 3440 (s), 2950 (s), 2865 (s), 1720 (s), 1460 (w), 1450 (w), 1430 (w), 1420 (w), 1385 (m), 1335 (m), 1310 (w), 1280 (m), 1260 (m), 1210 (w), 1155 (w), 1130 (w), 1120 (w), 1100 (w), 1075 (m), 1035 (s), 1010 (m), 990 (m), 970 (m), 930 (w), 920 (w), 860 (W), 840 (W), 795 (w), 710 (w), 680 (w).

NMR(H, 80MHz, CDCl₃/TMS);δ(ppm) : 0.60∼2.40(m,singlets at 0.68, 0.75, 0.82, 0.97, 1.02), 2.45∼2.85(1H, m). 3.45∼4.10(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS); δ (ppm): 0.60 to 2.40 (m, singlets at 0.68, 0.75, 0.82, 0.97, 1.02), 2.45 to 2.85 (1H, m). 3.45 to 4.10 (3H, m).

원소분석 : C₂₈H₄₈O₄ Elemental Analysis: C ₂₈ H ₄₈ O ₄

계산치(%) : C; 75.35, H; 10.82, O; 14.27Calculated (%): C; 75.35, H; 10.82, O; 14.27

실측치(%) : C; 74.82, H; 11.23, O; 13.83Found (%): C; 74.82, H; 11.23, 0; 13.83

[실시예 22]Example 22

2α,3α-디히드록시-20-[(1-히드록시-1-(2-메틸이소헥실)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1- (2-methylisohexyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76gr)과 2-메틸이소헥실마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 9 from compound (0.76 gr) and 2-methylisohexyl magnesium bromide.

융점 : 187∼191℃Melting Point: 187 ~ 191 ℃

; 3450(s), 2950(s), 2870(s), 1725(s), 1470(m), 1455(m), 1430(w), 1415(m), 1380(m), 1335(w), 1330(w), 1310(w), 1295(m), 1265(m), 1225(m), 1190(m), 1160(w), 1140(w), 1100(m), 1080(m), 1050(m), 1040(m), 1010(m), 980(m), 965(w), 950(w), 940(w), 920(w), 860(w), 705(w), 680(w), 645(w), 595(w), 556(w).

; 3450 (s), 2950 (s), 2870 (s), 1725 (s), 1470 (m), 1455 (m), 1430 (w), 1415 (m), 1380 (m), 1335 (w), 1330 (w), 1310 (w), 1295 (m), 1265 (m), 1225 (m), 1190 (m), 1160 (w), 1140 (w), 1100 (m), 1080 (m), 1050 (m), 1040 (m), 1010 (m), 980 (m), 965 (w), 950 (w), 940 (w), 920 (w), 860 (w), 705 (w), 680 (w), 645 (w), 595 (w), 556 (w).

NMR(1H, 80MHz, CDCl₃/TMS);δ(ppm) : 0.6∼2.40(m,singlets at 0.68, 0.80, 0.88, 0.92), 2.55∼2.80(1H, m), 3.45∼4.10(3H, m).NMR (1H, 80 MHz, CDCl ₃ / TMS); δ (ppm): 0.6-2.40 (m, singlets at 0.68, 0.80, 0.88, 0.92), 2.55-2.80 (1H, m), 3.45-4.10 (3H, m ).

원소분석 : C₂₉H₅₀O₄ Elemental Analysis: C ₂₉ H ₅₀ O ₄

실측치(%) : C; 74.76, H; 11.21, O; 13.74Found (%): C; 74.76, H; 11.21, O; 13.74

[실시예 23]Example 23

2α,3α-디히드록시-20-[(1-히드록시-1-(-2-메틸이소헥실)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1-(-2-methylisohexyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 2-메틸이소헵틸마그네슘브로마이드로부터 실시예 9와 동일한방법으로 제조하였다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and 2-methylisoheptyl magnesium bromide.

융점 : 198∼203℃Melting Point: 198 ~ 203 ℃

; 3450(s), 2960(s), 2865(s), 1725(s), 1470(m), 1450(m), 1415(m), 1385(m), 1340(w), 1330(w), 1310(w), 1275(m), 1235(m), 1200(m), 1160(w), 1140(w), 1100(m), 1080(m), 1055(m), 1040(m), 1005(m), 980(m), 920(m), 860(w), 815(w), 755(w), 705(w), 685(w), 645(w).

; 3450 (s), 2960 (s), 2865 (s), 1725 (s), 1470 (m), 1450 (m), 1415 (m), 1385 (m), 1340 (w), 1330 (w), 1310 (w), 1275 (m), 1235 (m), 1200 (m), 1160 (w), 1140 (w), 1100 (m), 1080 (m), 1055 (m), 1040 (m), 1005 (m), 980 (m), 920 (m), 860 (w), 815 (w), 755 (w), 705 (w), 685 (w), 645 (w).

NMR(1H, 80MHz, CDCl₃/TMS) : 0.60∼2.40(m, singlets at 0.65, 0.72, 1.05, 1.30, 1.07), 2.50∼2.75(1H, m), 3.50∼4.10(3H, m).NMR (1H, 80 MHz, CDCl ₃ / TMS): 0.60 to 2.40 (m, singlets at 0.65, 0.72, 1.05, 1.30, 1.07), 2.50 to 2.75 (1H, m), 3.50 to 4.10 (3H, m).

원소분석 : C₃₀H₅₂O₄ Elemental Analysis: C ₃₀ H ₅₂ O ₄

실측치(%) : C; 76.38, H; 10.42, O; 12.94Found (%): C; 76.38, H; 10.42, O; 12.94

[실시예 24]Example 24

2α,3α-디히드록시-20-[(1-히드록시-1-t-부틸)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1-t-butyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 1-t-부틸마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and 1-t-butylmagnesium bromide.

융점 : 172∼174℃Melting Point: 172 ~ 174 ℃

; 3450(s), 2960(s), 2870(s), 1725(s), 1465(m), 1450(m), 1415(m), 1385(m), 1340(w), 1330(w), 1310(w), 1275(m), 1230(m), 1195(m), 1160(w), 1150(w), 1100(m), 1080(m), 1055(m), 1040(m), 1055(m), 980(m), 920(m), 860(w), 815(w), 745(w), 705(w), 680(w), 645(w), 590(w).

; 3450 (s), 2960 (s), 2870 (s), 1725 (s), 1465 (m), 1450 (m), 1415 (m), 1385 (m), 1340 (w), 1330 (w), 1310 (w), 1275 (m), 1230 (m), 1195 (m), 1160 (w), 1150 (w), 1100 (m), 1080 (m), 1055 (m), 1040 (m), 1055 (m), 980 (m), 920 (m), 860 (w), 815 (w), 745 (w), 705 (w), 680 (w), 645 (w), 590 (w).

NMR(H, 80MHz, CDCl₃/TMS),δ(ppm) : 0.60∼2.40(m,singlets at 0.65, 0.72), 2.50∼2.75(1H, m), 3.50∼4.10(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS), δ (ppm): 0.60 to 2.40 (m, singlets at 0.65, 0.72), 2.50 to 2.75 (1H, m), 3.50 to 4.10 (3H, m).

원소분석 : C₂₆H₄₄O₄ Elemental Analysis: C ₂₆ H ₄₄ O ₄

실측치(%) : C; 74.23, H; 11.02, O; 15.47Found (%): C; 74.23, H; 11.02, O; 15.47

[실시예 25]Example 25

2α,3α-디히드록시-20-[(1-히드록시-1-t-헥실)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1-t-hexyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 1-t-헥실브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from Compound (II) (0.76 g) and 1-t-hexyl bromide.

융점 : 184∼185℃Melting Point: 184 ~ 185 ℃

; 3430(s), 2950(s), 2860(s), 1720(s), 1470(w), 1460(w), 1450(w), 1435(w), 1420(w), 1385(m), 1335(m), 1310(w), 1280(m), 1260(m), 1210(w), 1155(w), 1130(w), 1120(w), 1100(w), 1075(m), 1035(s), 1000(m), 985(m), 960(m), 930(w), 925(w), 860(w), 845(w), 795(w).

; 3430 (s), 2950 (s), 2860 (s), 1720 (s), 1470 (w), 1460 (w), 1450 (w), 1435 (w), 1420 (w), 1385 (m), 1335 (m), 1310 (w), 1280 (m), 1260 (m), 1210 (w), 1155 (w), 1130 (w), 1120 (w), 1100 (w), 1075 (m), 1035 (s), 1000 (m), 985 (m), 960 (m), 930 (w), 925 (w), 860 (w), 845 (w), 795 (w).

NMR(1H, 80MHz, CDCl₃/TMS);δ(ppm) : 0.60∼2.40(m,singlets at 0.68, 0.75, 0.90, 1.35), 2.45∼2.75(1H, m), 3.45∼4.20(3H, m)NMR (1H, 80 MHz, CDCl ₃ / TMS); δ (ppm): 0.60 to 2.40 (m, singlets at 0.68, 0.75, 0.90, 1.35), 2.45 to 2.75 (1H, m), 3.45 to 4.20 (3H, m )

원소분석 : C₂₈H₄₈O₄ Elemental Analysis: C ₂₈ H ₄₈ O ₄

실측치(%) : C; 74.72, H; 10.45, O; 14.48Found (%): C; 74.72, H; 10.45, O; 14.48

[실시예 26]Example 26

2α,3α-디히드록시-20-[(1-히드록시-1-t-옥틸)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1-t-octyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 1-t-옥틸마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from Compound (II) (0.76 g) and 1-t-octyl magnesium bromide.

융점 : 182∼186℃Melting Point: 182 ~ 186 ℃

; 3450(s), 2950(s), 2870(s), 1720(s), 1475(m), 1450(m), 1420(w), 1410(m), 1385(w), 1340(w), 1325(w), 1310(w), 1275(m), 1265(m), 1220(m), 1190(m), 1160(w), 1140(w), 1100(m), 1080(m), 1050(m), 1040(m), 1010(m), 975(m), 965(w), 950(w), 940(w), 920(w), 860(w), 705(w), 680(w), 645(w), 595(w).

; 3450 (s), 2950 (s), 2870 (s), 1720 (s), 1475 (m), 1450 (m), 1420 (w), 1410 (m), 1385 (w), 1340 (w), 1325 (w), 1310 (w), 1275 (m), 1265 (m), 1220 (m), 1190 (m), 1160 (w), 1140 (w), 1100 (m), 1080 (m), 1050 (m), 1040 (m), 1010 (m), 975 (m), 965 (w), 950 (w), 940 (w), 920 (w), 860 (w), 705 (w), 680 (w), 645 (w), 595 (w).

NMR(H, 80MHz, CDCl₃/TMS) : 0.60∼2.40(m,singlets at 0.68, 0.75, 0.80, 0.83, 0.90, 0.93), 2.50∼2.75(1H, m), 3.45∼4.10(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS): 0.60 to 2.40 (m, singlets at 0.68, 0.75, 0.80, 0.83, 0.90, 0.93), 2.50 to 2.75 (1H, m), 3.45 to 4.10 (3H, m) .

원소분석 : C₃₀H₅₂O₄ Elemental Analysis: C ₃₀ H ₅₂ O ₄

실측치(%) : C; 75.23, H; 11.24, O; 14.03Found (%): C; 75.23, H; 11.24, 0; 14.03

[실시예 27]Example 27

2α,3α-디히드록시-20-{(1-히드록시-1-메틸메틸술피닐헥)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-1-methylmethylsulfinylhex) methyl} -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 1-메틸메틸술피닐마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from Compound (II) (0.76 g) and 1-methylmethylsulfinylmagnesium bromide.

융점 : 197∼202℃Melting Point: 197 ~ 202 ℃

; 3450(s), 2875(m), 2815(w), 1725(s), 1470(m), 1450(m), 1430(m), 1385(m), 1350(w), 1340(w), 1325(w), 1310(w), 1280(w), 1260(w), 1230(w), 1200(w), 1160(w), 1130(w), 1115(w), 1100(m), 1070(m), 1035(m), 1005(m), 985(w), 965(m), 935(w), 920(w), 860(w), 710(w), 660(w).

; 3450 (s), 2875 (m), 2815 (w), 1725 (s), 1470 (m), 1450 (m), 1430 (m), 1385 (m), 1350 (w), 1340 (w), 1325 (w), 1310 (w), 1280 (w), 1260 (w), 1230 (w), 1200 (w), 1160 (w), 1130 (w), 1115 (w), 1100 (m), 1070 (m), 1035 (m), 1005 (m), 985 (w), 965 (m), 935 (w), 920 (w), 860 (w), 710 (w), 660 (w).

NMR(1H, 80MHz, CDCl₃/TMS);δ(ppm) : 0.60∼2.25(m,singlets at 0.67, 0.75, 1.9, 1.55), 2.52∼2.75(1H, m), 3.45∼4.20(8H, m).NMR (1H, 80 MHz, CDCl ₃ / TMS); δ (ppm): 0.60 to 2.25 (m, singlets at 0.67, 0.75, 1.9, 1.55), 2.52 to 2.75 (1H, m), 3.45 to 4.20 (8H, m ).

원소분석 : C₂₄H₄₀O₄SElemental Analysis: C ₂₄ H ₄₀ O ₄ S

계산치(%) : C; 67.94, H; 9.43, O; 15.08Calculated (%): C; 67.94, H; 9.43, 0; 15.08

실측치(%) : C; 68.23, H; 9.74, O; 14.75Found (%): C; 68.23, H; 9.74, O; 14.75

[실시예 28]Example 28

2α,3α-디히드록시-20-[1-히드록시-1-에톡시메틸)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- [1-hydroxy-1-ethoxymethyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 1-에톡시메틸마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from the compound of formula (II) (0.76 g) and 1-ethoxymethylmagnesium bromide.

융점 : 201∼204℃Melting Point: 201 ~ 204 ℃

; 3450(s), 2950(s), 2875(m), 1726(s), 1470(m), 1450(m), 1430(m), 1385(m), 1350(w), 1335(w), 1320(w), 1310(w), 1275(w), 1260(w), 1200(w), 1150(w), 1130(w), 1100(w), 1070(m), 1035(m), 1005(m), 985(w), 965(w), 940(w), 920(w), 860(w), 710(w), 660(w).

; 3450 (s), 2950 (s), 2875 (m), 1726 (s), 1470 (m), 1450 (m), 1430 (m), 1385 (m), 1350 (w), 1335 (w), 1320 (w), 1310 (w), 1275 (w), 1260 (w), 1200 (w), 1150 (w), 1130 (w), 1100 (w), 1070 (m), 1035 (m), 1005 (m), 985 (w), 965 (w), 940 (w), 920 (w), 860 (w), 710 (w), 660 (w).

NMR(1H, 80MHz, CDCl₃/TMS);δ(ppm) : 0.65∼2.20(m,singlets at 0.67, 0.73, 1.90, 1.25, 1.40), 2.50∼2.80(1H, m), 3.40∼4.20(7H, m).NMR (1H, 80 MHz, CDCl ₃ / TMS); δ (ppm): 0.65 to 2.20 (m, singlets at 0.67, 0.73, 1.90, 1.25, 1.40), 2.50 to 2.80 (1H, m), 3.40 to 4.20 (7H , m).

원소분석 : C₂₅H₄₂O₅ Elemental Analysis: C ₂₅ H ₄₂ O ₅

계산치(%) : C; 71.12, H; 9.95, O; 18.94Calculated (%): C; 71.12, H; 9.95, 0; 18.94

실측치(%) : C; 70.97, H; 10.23, O; 18.62Found (%): C; 70.97, H; 10.23, O; 18.62

[실시예 29]Example 29

2α,3α-디히드록시-20-[(1-히드록시-1-시클로헥실)메틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[(1-hydroxy-1-cyclohexyl) methyl] -5α-pregnan-6-one

일반식(II)화합물(0.76g)과 시클로헥실마그네슘브로마이드로부터 실시예 9와 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 9 from compound (II) (0.76 g) and cyclohexyl magnesium bromide.

중간체인 6,6-에틸렌옥시-2α,3α-이소프로필리덴-디옥시-20-[(1-히드록시-1-시클로헥실)메틸]-5α-프레그난-6온의 데이터는 아래와 같다.The data of the intermediate 6,6-ethyleneoxy-2α, 3α-isopropylidene-dioxy-20-[(1-hydroxy-1-cyclohexyl) methyl] -5α-pregnan-6one are as follows.

융점 : 106∼109℃Melting Point: 106 ~ 109 ℃

수율 : 65%Yield: 65%

; 3475(m), 2900(s), 2830(s), 1450(m), 1380(m), 1340(w), 1310(w), 1290(w), 1265(w), 1250(w), 1230(w), 1225(w), 1200(m), 1180(m), 1130(m), 1090(s), 1070(s), 1050(s), 995(m), 970(m), 935(w), 905(w), 895(w), 880(w), 820(W), 750(w).

; 3475 (m), 2900 (s), 2830 (s), 1450 (m), 1380 (m), 1340 (w), 1310 (w), 1290 (w), 1265 (w), 1250 (w), 1230 (w), 1225 (w), 1200 (m), 1180 (m), 1130 (m), 1090 (s), 1070 (s), 1050 (s), 995 (m), 970 (m), 935 (w), 905 (w), 895 (w), 880 (w), 820 (W), 750 (w).

NMR(60MHz, CDCl₃/TMS)δ(ppm) : 0.67∼2.40(m,singlets at 0.70, 0.83, 0.90, 1.07, 1.20, 1.26, 1.40, 1.50, 1.67), 3.10∼3.40(1H, m), 3.40∼4.40(6H, m).NMR (60 MHz, CDCl ₃ / TMS) δ (ppm): 0.67-2.40 (m, singlets at 0.70, 0.83, 0.90, 1.07, 1.20, 1.26, 1.40, 1.50, 1.67), 3.10-3.40 (1H, m), 3.40 to 4.40 (6H, m).

보호기를 제거한 표제 화합물의 데이터는 아래와 같다.The data of the title compound without protecting group is as follows.

융점 : 163∼166℃Melting Point: 163 ~ 166 ℃

수율 : 81.6%Yield: 81.6%

; 3400(s), 2940(s), 2870(s), 1730(s), 1470(w), 1460(m), 1430(m), 1390(m), 1360(w), 1340(w), 1330(w), 1315(w), 1275(m), 1230(m), 1200(m), 1120(w), 1100(m), 1080(m), 1065(m), 1040(m), 1030(m), 1010(m), 975(m), 935(w), 920(w), 880(w), 710(w), 680(w), 650(w), 645(w), 590(w).

; 3400 (s), 2940 (s), 2870 (s), 1730 (s), 1470 (w), 1460 (m), 1430 (m), 1390 (m), 1360 (w), 1340 (w), 1330 (w), 1315 (w), 1275 (m), 1230 (m), 1200 (m), 1120 (w), 1100 (m), 1080 (m), 1065 (m), 1040 (m), 1030 (m), 1010 (m), 975 (m), 935 (w), 920 (w), 880 (w), 710 (w), 680 (w), 650 (w), 645 (w), 590 (w).

NMR(H, 60MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.45(m,singlets at 0.67, 0.75, 0.84, 0.90, 1.65, 1.80), 2.55∼2.83(1H, m), 3.10∼3.30(1H, m), 3.60∼4.15(2H, m)NMR (H, 60 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.45 (m, singlets at 0.67, 0.75, 0.84, 0.90, 1.65, 1.80), 2.55 to 2.83 (1H, m), 3.10 to 3.30 ( 1H, m), 3.60 to 4.15 (2H, m)

원소분석 : C₂₈H₄₇O₄ Elemental Analysis: C ₂₈ H ₄₇ O ₄

계산치(%) : C; 75.19, H; 10.51, O; 14.30Calculated (%): C; 75.19, H; 10.51, O; 14.30

실측치(%) : C; 75.51, H; 10.42, O; 14.19Found (%): C; 75.51, H; 10.42, O; 14.19

[실시예 30]Example 30

2α,3α-디히드록시-20-(1-히드록시-1-페닐메틸)-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- (1-hydroxy-1-phenylmethyl) -5α-pregnan-6-one

일반식(II)화합물(0.76g)을 건조 에테르(20ml)에 녹인 후에 페닐마그네슘브로마이드(0.5ml, 10N stock soln in ether)을 실온에서 교반하면서 서서히 더하여 준다.Compound (II) (0.76 g) was dissolved in dry ether (20 ml) and phenylmagnesium bromide (0.5 ml, 10N stock soln in ether) was added slowly while stirring at room temperature.

30분후에 반응 혼합물을 1시간 가량 환류시킨 다음, 물(10ml)을 적가한다. 반 혼합물을 묽은 염산으로 씻은 뒤, 에테르층을 분리하고, 건조 황산마그네슘으로 탈수한 후 감압 증발시킨다. 이때 얻어진 불순 잔여물을 컬럼 크로마토그래피(실리카겔 70∼200메쉬, 헥산 : 에틸아세티이트 = 4 : 1)하여 정제한다. 이때 6,6-에틸렌-디옥시-2α,3α-이소프로필리덴 디옥시-20-(1-히드록시-1-페닐메틸)-5α-프레그난이 얻어졌다.(0.52gr, 57.8%)After 30 minutes, the reaction mixture is refluxed for about 1 hour and then water (10 ml) is added dropwise. The half mixture was washed with dilute hydrochloric acid, the ether layer was separated, dehydrated with dry magnesium sulfate and evaporated under reduced pressure. The resulting impurity residue is purified by column chromatography (silica gel 70-200 mesh, hexane: ethyl acetate = 4: 1). 6,6-Ethylene-dioxy-2α, 3α-isopropylidene dioxy-20- (1-hydroxy-1-phenylmethyl) -5α-pregnan was obtained. (0.52gr, 57.8%)

융점 : 106~108℃Melting Point: 106 ~ 108 ℃

; 3500(m), 2955(s), 2890(s), 1500(w), 1470(m), 1455(m), 1385(m), 1345(w), 1305(w), 1285(w), 1240(m), 1215(m), 1190(m), 1165(m), 1145(m), 1125(m), 1080(s), 1050(s), 1040(s), 975(m), 950(m), 905(w), 870(w), 855(w), 830(w), 680(m), 660(w), 645(w), 635(w), 590(w), 560(w).

; 3500 (m), 2955 (s), 2890 (s), 1500 (w), 1470 (m), 1455 (m), 1385 (m), 1345 (w), 1305 (w), 1285 (w), 1240 (m), 1215 (m), 1190 (m), 1165 (m), 1145 (m), 1125 (m), 1080 (s), 1050 (s), 1040 (s), 975 (m), 950 (m), 905 (w), 870 (w), 855 (w), 830 (w), 680 (m), 660 (w), 645 (w), 635 (w), 590 (w), 560 (w).

NMR(H, 60MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.40(m,singlets at 0.70, 0.80, 1.0, 1.23, 1.35, 1.62, 1.70), 3.65∼4.35(6H, m), 4.7∼5.0(1H,s), 7.25∼7.5(5H,s). 상기 알코올(0.5g)을 THF(20ml)에 녹인 후 에, 6N염산(5ml)을 첨가하고 실온에서 교반한다(12시간).NMR (H, 60 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.40 (m, singlets at 0.70, 0.80, 1.0, 1.23, 1.35, 1.62, 1.70), 3.65 to 4.35 (6H, m), 4.7 to 5.0 (1H, s), 7.25-7.5 (5H, s). After dissolving the alcohol (0.5 g) in THF (20ml), 6N hydrochloric acid (5ml) is added and stirred at room temperature (12 hours).

용매를 제거한 후 잔사를 컬럼 크로마토그래피 하여 정제한다. 헥산 에테르 하에서 잘 처리하면 0.22gr의 고형물의 표제 화합물이 얻어진다.After removing the solvent, the residue is purified by column chromatography. Good treatment under hexane ether yields 0.22 gr of the title compound as a solid.

융점 : 171∼174℃Melting Point: 171 ~ 174 ℃

수율 : 50.2%Yield: 50.2%

; 3450(s), 2950(s), 2880(s), 1715(s), 1500(w), 1460(m), 1455(m), 1385(s), 1335(w), 1325(w), 1310(w), 1275(w), 1260(w), 1230(w), 1200(w), 1160(w), 1100(w), 1075(s), 1030(s), 1005(m), 980(m), 960(w), 930(w), 920(w), 860(w), 790(w), 730(w), 680(m), 590(w)

; 3450 (s), 2950 (s), 2880 (s), 1715 (s), 1500 (w), 1460 (m), 1455 (m), 1385 (s), 1335 (w), 1325 (w), 1310 (w), 1275 (w), 1260 (w), 1230 (w), 1200 (w), 1160 (w), 1100 (w), 1075 (s), 1030 (s), 1005 (m), 980 (m), 960 (w), 930 (w), 920 (w), 860 (w), 790 (w), 730 (w), 680 (m), 590 (w)

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.80(m,singlets at 0.70, 0.75, 1.30, 1.65), 3.50∼4.15(2H, m), 4.9(1H,s), 7.25(5H,s)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.80 (m, singlets at 0.70, 0.75, 1.30, 1.65), 3.50 to 4.15 (2H, m), 4.9 (1H, s), 7.25 (5H, s)

원소분석(C₂₈H₄₀O₄)Elemental Analysis (C ₂₈ H ₄₀ O ₄ )

계산치(%) : C; 76.39, H; 9.09, O; 14.53Calculated (%): C; 76.39, H; 9.09, O; 14.53

실측치(%) : C; 76.28, H; 9.43, O; 14.72Found (%): C; 76.28, H; 9.43, 0; 14.72

[실시예 31]Example 31

2α,3α-디히드록시-20-{(1-히드록시-3-페닐)프로필}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-3-phenyl) propyl} -5α-pregnan-6-one

상기 실시예 30과 동일한 방법으로 일반식(II)화합물과 페닐에틸마그네슘브로마이드와 반응시켜 표제화합물을 제조하였다. 최종 생성물의 데이터는 아래와 같다.In the same manner as in Example 30, the title compound was prepared by reacting the compound of General Formula (II) with phenylethylmagnesium bromide. The data of the final product is as follows.

융점 214~217℃ 수율 : 58.8%Melting Point 214 ~ 217 ℃ Yield: 58.8%

; 3450(s), 2960(s), 2870(m), 1725(s), 1615(w), 1505(w), 1475(w), 1460(m), 1430(m), 1420(m), 1395(m), 1390(m), 1340(w), 1330(w), 1310(m), 1295(w), 1275(m), 1235(m), 1195(m), 1170(w), 1165(w), 1100(m), 1075(m), 1040(m), 1030(m), 1007(m), 975(w), 965(m), 940(w), 920(m), 890(w), 880(w), 860(w), 820(w), 785(w), 720(m), 680(m), 645(w), 595(w), 575(w), 555(w), 460(w)

; 3450 (s), 2960 (s), 2870 (m), 1725 (s), 1615 (w), 1505 (w), 1475 (w), 1460 (m), 1430 (m), 1420 (m), 1395 (m), 1390 (m), 1340 (w), 1330 (w), 1310 (m), 1295 (w), 1275 (m), 1235 (m), 1195 (m), 1170 (w), 1165 (w), 1100 (m), 1075 (m), 1040 (m), 1030 (m), 1007 (m), 975 (w), 965 (m), 940 (w), 920 (m), 890 (w), 880 (w), 860 (w), 820 (w), 785 (w), 720 (m), 680 (m), 645 (w), 595 (w), 575 (w), 555 (w), 460 (w)

NMR(H, 80MHz, CDC₃/TMS)δ(ppm) : 0.60∼2.40(m, singlets at 0.66, 0.74, 1.68, 1.83, 1.97), 2.50∼2.83(30H, m), 3.55~4.1(3H, m), 7.17(5H,s)NMR (H, 80 MHz, CDC ₃ / TMS) δ (ppm): 0.60 to 2.40 (m, singlets at 0.66, 0.74, 1.68, 1.83, 1.97), 2.50 to 2.83 (30H, m), 3.55 to 4.1 (3H, m), 7.17 (5H, s)

원소분석(C₃₀H₄₄O₄)Elemental Analysis (C ₃₀ H ₄₄ O ₄ )

계산치(%) : C; 76.94, H; 9.40, O; 13.66Calculated (%): C; 76.94, H; 9.40, 0; 13.66

실측치(%) : C; 76.28, H; 9.43, O; 13.74Found (%): C; 76.28, H; 9.43, 0; 13.74

[실시예 32]Example 32

2α,3α-디히드록시-20-{(1-히드록시-2-페닐)에틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-2-phenyl) ethyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)을 건조 에테르(20ml)에 녹이고, 벤질마그네슘브로마이드(0.5ml, 10N 에테르 용액)을 상온에서 교반을 시키면서 서서히 첨가하였다. 30분 후에, 반응 혼합물을 30분간 환류시켰다. 그런 다음에 물(10ml)을 반응 용액을 냉각시키면서 적가하였다. 묽은 염산으로 반응 혼합물을 세척한 후에 에테르 층을 분리하여, 무수 황산 마그네슘으로 건조시킨 후에 감압증발하였다. 이때 유상의 잔사가 얻어졌다.(0.65g, 69.9%). 컬럼 크로마토그래피(실리카겔 230∼400메쉬, 헥산 : 에틸 아세테이트 = 4:1)하여 정제하였다.

위의 잔사(0.55g)을 THF(20ml)에 녹이고 6N염산(5ml)을 첨가하고 밤새도록 교반하였다. 모든 성분을 감압 증발 건조시킨 잔사를 컬럼 크로마코그래피(실리카 겔 70∼200메쉬, 클로로포름 : 메탄올 = 40 : 1)로 정제하였다. 이를 헥산-에테르 하에서 잘 비벼 표제 화합물이 0.35g 얻어졌다.Compound (II) (0.76 g) was dissolved in dry ether (20 ml), and benzyl magnesium bromide (0.5 ml, 10N ether solution) was added slowly with stirring at room temperature. After 30 minutes, the reaction mixture was refluxed for 30 minutes. Water (10 ml) was then added dropwise while cooling the reaction solution. After washing the reaction mixture with dilute hydrochloric acid, the ether layer was separated, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. An oily residue was obtained at this time (0.65 g, 69.9%). Purification was carried out by column chromatography (silica gel 230-400 mesh, hexane: ethyl acetate = 4: 1).

The residue (0.55 g) was dissolved in THF (20 ml) and 6N hydrochloric acid (5 ml) was added and stirred overnight. The residue from which all components were evaporated to dryness under reduced pressure was purified by column chromatography (silica gel 70 to 200 mesh, chloroform: methanol = 40: 1). This was rubbed well under hexane-ether to obtain 0.35 g of the title compound.

융점 : 183∼185℃Melting Point: 183 ~ 185 ℃

수율 : 72%Yield: 72%

; 3325(s), 2900(s), 2825(m), 1700(s), 1600(w), 1460(m), 1455(m), 1420(m), 1380(m), 1340(w), 1310(w), 1280(m), 1260(w), 1230(w), 1205(w), 1105(w), 1090(s), 1045(m), 1020(m), 990(m), 950(w), 940(w), 880(w), 760(w), 755(w), 710(m).

; 3325 (s), 2900 (s), 2825 (m), 1700 (s), 1600 (w), 1460 (m), 1455 (m), 1420 (m), 1380 (m), 1340 (w), 1310 (w), 1280 (m), 1260 (w), 1230 (w), 1205 (w), 1105 (w), 1090 (s), 1045 (m), 1020 (m), 990 (m), 950 (w), 940 (w), 880 (w), 760 (w), 755 (w), 710 (m).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.63, 0.74), 2.45∼3.0(3H, m), 3.55∼4.12(3H, m), 7.25(5H,s)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.74), 2.45 to 3.0 (3H, m), 3.55 to 4.12 (3H, m), 7.25 (5H , s)

원소분석(C₂₉H₄₂O₄)Elemental Analysis (C ₂₉ H ₄₂ O ₄ )

계산치(%) : C; 76.67, H; 9.25, O; 14.08Calculated (%): C; 76.67, H; 9.25, O; 14.08

실측치(%) : C; 75.94, H; 9.72, O; 13.24Found (%): C; 75.94, H; 9.72, 0; 13.24

[실시예 33]Example 33

2α,3α-디히드록시-20{[1-히드록시-2-(0-메틸 페닐)]}에틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 {[1-hydroxy-2- (0-methylphenyl)]} ethyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 0-메틸벤질마그네슘 브로마이드로부터 실시예 30과 동일하게 반응시켜 표제 화합물을 제조했다.The title compound was prepared in the same manner as in Example 30 from General Formula (II) Compound (0.76 g) and 0-methylbenzylmagnesium bromide.

융점 : 234∼237℃Melting Point: 234 ~ 237 ℃

수율 : 61.5%Yield: 61.5%

; 3420(s), 2950(s), 2880(s), 1725(s), 1500(w), 1470(w), 1460(w), 1430(w), 1385(w), 1315(w), 1280(w), 1255(w), 1230(m), 1100(m), 1075(m), 1040(m), 1005(m), 980(m), 920(w), 860(w), 800(w), 730(m), 705(w), 680(w), 640(w), 480(w), 400(w).

; 3420 (s), 2950 (s), 2880 (s), 1725 (s), 1500 (w), 1470 (w), 1460 (w), 1430 (w), 1385 (w), 1315 (w), 1280 (w), 1255 (w), 1230 (m), 1100 (m), 1075 (m), 1040 (m), 1005 (m), 980 (m), 920 (w), 860 (w), 800 (w), 730 (m), 705 (w), 680 (w), 640 (w), 480 (w), 400 (w).

NMR (H, 80MHz, CDCl₃TMS)δ(ppm) : 0.6∼2.15(m, singlets at 0.67, 0.75), 2.30(3H,s), 2.50∼2.82(3H, m), 3.57∼4.10(3H, m), 7.12(4H, s)NMR (H, 80 MHz, CDCl ₃ TMS) δ (ppm): 0.6 to 2.15 (m, singlets at 0.67, 0.75), 2.30 (3H, s), 2.50 to 2.82 (3H, m), 3.57 to 4.10 (3H, m), 7.12 (4H, s)

원소분석(C₃₀H₄₄O₄)Elemental Analysis (C ₃₀ H ₄₄ O ₄ )

실측치(%) : C; 77.12, H; 9.77, O; 13.27Found (%): C; 77.12, H; 9.77, O; 13.27

[실시예 34]Example 34

2α,3α-디히드록시-20-{[1-히드록시-2-(m-메틸 페닐)}에틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{[1-hydroxy-2- (m-methylphenyl)} ethyl] -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 n-메틸벤질마그네슘 브로마이드로부터 실시예 30과 동일한 방법으로 반응시켜 표제 화합물을 제조했다.The title compound was prepared in the same manner as in Example 30 from General Formula (II) Compound (0.76 g) and n-methylbenzylmagnesium bromide.

융점 : 208∼210℃Melting Point: 208 ~ 210 ℃

수율 : 68.4%Yield: 68.4%

; 3440(s), 2955(s), 2870(m), 1725(s), 1620(w), 1470(w), 1460(w), 1445(w), 1400(w), 1430(w), 1385(m), 1310(w), 1275(m), 1230(m), 1200(m), 1100(w), 1070(m), 960(w), 920(w), 860(w), 780(w), 760(w), 730(w), 680(w), 640(w), 590(w), 440(w).

; 3440 (s), 2955 (s), 2870 (m), 1725 (s), 1620 (w), 1470 (w), 1460 (w), 1445 (w), 1400 (w), 1430 (w), 1385 (m), 1310 (w), 1275 (m), 1230 (m), 1200 (m), 1100 (w), 1070 (m), 960 (w), 920 (w), 860 (w), 780 (w), 760 (w), 730 (w), 680 (w), 640 (w), 590 (w), 440 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.15(m,singlets at 0.65, 0.74), 2.31(3H,s), 2.50∼2.90(3H, m), 3.55∼4.20(3H, m), 6.98(4H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.15 (m, singlets at 0.65, 0.74), 2.31 (3H, s), 2.50 to 2.90 (3H, m), 3.55 to 4.20 (3H m), 6.98 (4H, s).

원소분석(C₃₀H₄₄O₄)Elemental Analysis (C ₃₀ H ₄₄ O ₄ )

실측치(%) : C; 76.54, H; 9.48, O; 13.76Found (%): C; 76.54, H; 9.48, 0; 13.76

[실시예 35]Example 35

2α,3α-디히드록시-20[{1-히드록시-2-(p-메틸 페닐)}에틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 [{1-hydroxy-2- (p-methyl phenyl)} ethyl] -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 p-메틸벤질마그네슘 브로마이드로부터 실시예 30과 동일하게 반응시켜 표제화합물을 제조했다.The title compound was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and p-methylbenzylmagnesium bromide.

융점 : 208∼210℃Melting Point: 208 ~ 210 ℃

수율 : 68.4%Yield: 68.4%

; 3350(s), 2900(s), 2825(S), 1705(s), 1510(w), 1460(m), 1440(m), 1420(m), 1410(w), 1380(m), 1340(w), 1310(w), 1280(w), 1260(w), 1240(w), 1210(w), 1170(w), 1160(w), 1130(m), 1110(m), 1090(s), 1050(s), 1020(m), 1000(m), 990(m), 960(m), 880(w), 820(w), 810(w), 800(w), 710(w), 600(w), 560(w), 500(w).

; 3350 (s), 2900 (s), 2825 (S), 1705 (s), 1510 (w), 1460 (m), 1440 (m), 1420 (m), 1410 (w), 1380 (m), 1340 (w), 1310 (w), 1280 (w), 1260 (w), 1240 (w), 1210 (w), 1170 (w), 1160 (w), 1130 (m), 1110 (m), 1090 (s), 1050 (s), 1020 (m), 1000 (m), 990 (m), 960 (m), 880 (w), 820 (w), 810 (w), 800 (w), 710 (w), 600 (w), 560 (w), 500 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.6∼2.15(m,singlets at 0.64, 0.74, 1.70), 2.30(3H,s), 2.50∼2.60(3H, m), 3.55∼4.10(3H, m), 7.07(4H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.6 to 2.15 (m, singlets at 0.64, 0.74, 1.70), 2.30 (3H, s), 2.50 to 2.60 (3H, m), 3.55 to 4.10 (3H, m), 7.07 (4H, s).

원소분석(C₃₀H₄₄O₄)Elemental Analysis (C ₃₀ H ₄₄ O ₄ )

실측치(%) : C; 76.84, H; 9.79, O; 13.24Found (%): C; 76.84, H; 9.79, O; 13.24

[실시예 36]Example 36

2α,3α-디히드록시-20[{1-히드록시-2-(P-에틸페닐)}에틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 [{1-hydroxy-2- (P-ethylphenyl)} ethyl] -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 p-에틸벤질마그네슘 브로마이드로부터 실시예 30의 방법과 동일하게 반응시켜 표제화합물을 얻었다.The title compound was obtained in the same manner as in Example 30 from General Formula (II) Compound (0.76 g) and p-ethylbenzylmagnesium bromide.

융점 : 209∼213℃Melting Point: 209 ~ 213 ℃

수율 : 52.9%Yield: 52.9%

; 3350(s), 2900(s), 2830(m), 1700(s), 1510(w), 1460(m), 1440(m), 1405(w), 1305(w), 1280(w), 1260(w), 1250(w), 1230(w), 1210(w), 1195(w), 1180(w), 1170(w), 1120(w), 1095(m), 1050(m), 1020(m), 990(m), 960(w), 940(w), 890(w), 850(w), 820(w), 770(w), 670(w), 600(w).

; 3350 (s), 2900 (s), 2830 (m), 1700 (s), 1510 (w), 1460 (m), 1440 (m), 1405 (w), 1305 (w), 1280 (w), 1260 (w), 1250 (w), 1230 (w), 1210 (w), 1195 (w), 1180 (w), 1170 (w), 1120 (w), 1095 (m), 1050 (m), 1020 (m), 990 (m), 960 (w), 940 (w), 890 (w), 850 (w), 820 (w), 770 (w), 670 (w), 600 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.63, 0.73, 1.10, 1.19, 1.28, 1.47, 1.63, 1.80, 1.95), 2.40∼2.80(5H, m), 3.55∼4.15(3H, m), 7.08(4H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.73, 1.10, 1.19, 1.28, 1.47, 1.63, 1.80, 1.95), 2.40 to 2.80 (5H, m ), 3.55 to 4.15 (3H, m), 7.08 (4H, s).

원소분석(C₃₁H₄₆O₄)Elemental Analysis (C ₃₁ H ₄₆ O ₄ )

계산치(%) : C; 77.20, H; 9.54, O; 13.26Calculated (%): C; 77.20, H; 9.54, 0; 13.26

실측치(%) : C; 76.84, H; 9.42, O; 13.77Found (%): C; 76.84, H; 9.42, O; 13.77

[실시예 37]Example 37

2α,3α-디히드록시-20-[{1-히드록시-2-(p-이소프로필페닐)}에틸]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-[{1-hydroxy-2- (p-isopropylphenyl)} ethyl] -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 p-이소프로필마그네슘브로마이드로부터 실시예 30의 방법과 동일하게 반응시켜 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 30 from General Formula (II) Compound (0.76 g) and p-isopropylmagnesium bromide.

융점 : 216∼219℃Melting Point: 216 ~ 219 ℃

수율 : 59.4%Yield: 59.4%

; 3430(s), 2960(s), 2880(m), 1725(s), 1520(w), 1470(m), 1450(m), 1430(w), 1385(m), 1330(w), 1315(w), 1280(w), 1260(w), 1235(w), 1205(w), 1100(w), 1070(m), 1040(m), 1005(m), 975(m), 925(w), 860(w), 800(w), 690(w), 640(w), 590(w), 580(w).

; 3430 (s), 2960 (s), 2880 (m), 1725 (s), 1520 (w), 1470 (m), 1450 (m), 1430 (w), 1385 (m), 1330 (w), 1315 (w), 1280 (w), 1260 (w), 1235 (w), 1205 (w), 1100 (w), 1070 (m), 1040 (m), 1005 (m), 975 (m), 925 (w), 860 (w), 800 (w), 690 (w), 640 (w), 590 (w), 580 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.45(m,singlets at 0.64, 0.73, 1.17, 1.26, 1.47, 1.62, 1.80, 1.95, 2.10, 2.20), 2.50∼3.0(4H, m), 3.55∼4.1(3H, m), 7.10(4H, s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.45 (m, singlets at 0.64, 0.73, 1.17, 1.26, 1.47, 1.62, 1.80, 1.95, 2.10, 2.20), 2.50 to 3.0 (4H m), 3.55 to 4.1 (3H, m), 7.10 (4H, s).

원소분석(C₃₂H₄₈O4₎ Elemental Analysis (C ₃₂ H ₄₈ O4 ₎

계산치(%) : C; 77.44, H; 9.67, O; 12.89Calculated (%): C; 77.44, H; 9.67, 0; 12.89

실측치(%) : C; 77.64, H; 9.69, O; 12.43Found (%): C; 77.64, H; 9.69, 0; 12.43

[실시예 38]Example 38

2α,3α-디히드록시-20[{1-히드록시-2-페닐}에테닐]-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 [{1-hydroxy-2-phenyl} ethenyl] -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 스티렌마그네슘브로마이드로부터 실시예 30과 동일하게 반응시켜 표제 화합물을 제조하였다.The title compound was prepared in the same manner as in Example 30 from General Formula (II) Compound (0.76 g) and styrenemagnesium bromide.

융점 : 184∼189℃Melting Point: 184 ~ 189 ℃

수율 : 82%Yield: 82%

; 3470(s), 2950(s), 2890(s), 1720(s), 1645(w), 1605(w), 1505(w), 1385(m), 1375(m), 1355(m), 1340(m), 1315(m), 1290(m), 1260(m), 1240(m), 1160(w), 1150(w), 1100(m), 1075(m), 1045(s), 1030(s), 1010(m), 985(w), 950(s), 945(w), 910(w), 865(w), 730(s), 670(m), 595(w), 550(w), 510(w).

; 3470 (s), 2950 (s), 2890 (s), 1720 (s), 1645 (w), 1605 (w), 1505 (w), 1385 (m), 1375 (m), 1355 (m), 1340 (m), 1315 (m), 1290 (m), 1260 (m), 1240 (m), 1160 (w), 1150 (w), 1100 (m), 1075 (m), 1045 (s), 1030 (s), 1010 (m), 985 (w), 950 (s), 945 (w), 910 (w), 865 (w), 730 (s), 670 (m), 595 (w), 550 (w), 510 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.50∼2.45(m,singlets at 0.60, 0.75, 1.50, 1.35, 1.85), 2.50∼2.83(1H, m), 3.55∼4.20(3H, m), 5.90∼5.55(2H, m), 6.80∼7.50(5H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.50 to 2.45 (m, singlets at 0.60, 0.75, 1.50, 1.35, 1.85), 2.50 to 2.83 (1H, m), 3.55 to 4.20 (3H, m), 5.90-5.55 (2H, m), 6.80-7.50 (5H, m).

원소분석(C₂₉H₄₀O₄)Elemental Analysis (C ₂₉ H ₄₀ O ₄ )

계산치(%) : C; 77.01, H; 8.85, O; 14.14Calculated (%): C; 77.01, H; 8.85, O; 14.14

실측치(%) : C; 76.27, H; 8.23, O; 13.49Found (%): C; 76.27, H; 8.23, O; 13.49

[실시예 39]Example 39

2α,3α-디히드록시-20[1-히드록시-1-(2-피코일)]메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 [1-hydroxy-1- (2-phycoyl)] methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-피코일 마그네슘브로마이드로부터 실시예 30과 동일한 방법으로 제조하였다.It was prepared according to the same method as Example 30 from compound (II) (0.76 g) and 2-picoyl magnesium bromide.

융점 : 178∼181℃Melting Point: 178 ~ 181 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1570(m), 1535(m), 1460(m), 1455(m), 1420(m), 1330(w), 1310(w), 1280(m), 1260(m), 1230(w), 1210(w), 1100(w), 1090(s), 1045(m), 1000(w), 990(m), 950(w), 940(w), 880(w), 760(w), 750(m).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1570 (m), 1535 (m), 1460 (m), 1455 (m), 1420 (m), 1330 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1210 (w), 1100 (w), 1090 (s), 1045 (m), 1000 (w), 990 (m), 950 (w), 940 (w), 880 (w), 760 (w), 750 (m).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.63, 0.75, 0.87), 2.45∼3.0(3H, m), 3.55∼4.12(3H, m), 6.80∼8.60(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.75, 0.87), 2.45 to 3.0 (3H, m), 3.55 to 4.12 (3H, m), 6.80 -8.60 (4H, m).

원소분석(C₂₈H₄₁O₄N)Elemental Analysis (C ₂₈ H ₄₁ O ₄ N)

계산치(%) : C; 73.87, H; 9.00, O; 14.05Calculated (%): C; 73.87, H; 9.00, 0; 14.05

실측치(%) : C; 74.32, H; 8.38, O; 13.26Found (%): C; 74.32, H; 8.38, 0; 13.26

[실시예 40]Example 40

2α,3α-디히드록시-20{1-히드록시-1-(3-메틸-2-피코일)}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20 {1-hydroxy-1- (3-methyl-2-picoyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 3-메틸-2-피코일마그네슘브로마이드로부터 실시예 30과 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 3-methyl-2-picoylmagnesium bromide.

융점 : 182∼185℃Melting Point: 182 ~ 185 ℃

; 3440(s), 2950(s), 2850(s), 1720(s), 1570(w), 1540(m), 1450(m), 1440(m), 1420(m), 1330(w), 1310(w), 1280(m), 1260(m), 1230(w), 1205(w), 1100(w), 1095(s), 1045(m), 1000(w), 985(m), 950(w), 935(w), 880(w), 760(w), 750(m)

; 3440 (s), 2950 (s), 2850 (s), 1720 (s), 1570 (w), 1540 (m), 1450 (m), 1440 (m), 1420 (m), 1330 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1205 (w), 1100 (w), 1095 (s), 1045 (m), 1000 (w), 985 (m), 950 (w), 935 (w), 880 (w), 760 (w), 750 (m)

NMR(1H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.63, 0.75, 0.87, 0.95), 2.40∼3.05(6H, m), 3.55∼4.12(3H, m), 6.80∼8.60(3H, m)NMR (1H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.75, 0.87, 0.95), 2.40 to 3.05 (6H, m), 3.55 to 4.12 (3H, m) , 6.80-8.60 (3H, m)

원소분석(C₂₉H₄₃O₄N)Elemental Analysis (C ₂₉ H ₄₃ O ₄ N)

계산치(%) : C; 74.22, H; 9.16, O; 13.63Calculated (%): C; 74.22, H; 9.16, O; 13.63

실측치(%) : C; 73.49, H; 9.79, O; 14.21Found (%): C; 73.49, H; 9.79, O; 14.21

[실시예 41]Example 41

2α,3α-디히드록시-20-{1-히드록시-1-(5-메틸-2-피코일)}메틸-5α-프레그난-6-온의 제조.Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (5-methyl-2-picoyl)} methyl-5α-pregnan-6-one.

일반식(II) 화합물(0.76g)과 5-메틸-2-피코일마그네슘브로마이드로부터 실시예 30과 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 5-methyl-2-picoylmagnesium bromide.

융점 : 179∼182℃Melting Point: 179 ~ 182 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1570(m), 1540(m), 1450(m), 1440(m), 1425(m), 1340(w), 1310(w), 1280(m), 1260(m), 1230(w), 1205(w), 1100(w), 1095(s), 1045(m), 995(w), 985(m), 955(w), 940(w), 880(m), 760(w), 745(m), 680(w), 625(w).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1570 (m), 1540 (m), 1450 (m), 1440 (m), 1425 (m), 1340 (w), 1310 (w), 1280 (m), 1260 (m), 1230 (w), 1205 (w), 1100 (w), 1095 (s), 1045 (m), 995 (w), 985 (m), 955 (w), 940 (w), 880 (m), 760 (w), 745 (m), 680 (w), 625 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.25(m,singlets at 0.63, 0.75), 2.40∼3.05(6H, m), 3.50∼4.15(3H, m), 6.80∼8.60(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.75), 2.40 to 3.05 (6H, m), 3.50 to 4.15 (3H, m), 6.80 to 8.60 (3H, m).

원소분석(C₂₉H₄₃O₄N)Elemental Analysis (C ₂₉ H ₄₃ O ₄ N)

실측치(%) : C; 75.21, H; 8.79, O; 14.24Found (%): C; 75.21, H; 8.79, 0; 14.24

[실시예 42]Example 42

2α,3α-디히드록시-20-{1-히드록시-1-(3-피코일)}메틸-5α-프레그난-6-온의 제조.Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (3-phycoyl)} methyl-5α-pregnan-6-one.

일반식(II) 화합물(0.76g)과 3-피코일마그네슘브로마이드로부터 실시예 30과 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 3-PicoylMagnesium Bromide.

융점 : 187∼190℃Melting Point: 187 ~ 190 ℃

; 3455(s), 2950(s), 2850(s), 1720(s), 1585(m), 1540(m), 1455(m), 1445(m), 1420(m), 1310(w), 1295(m), 1280(m), 1260(m), 1230(w), 1205(w), 1100(w), 1095(s), 1040(m), 990(m), 980(m), 960(w), 940(w), 890(m), 760(w), 745(m), 680(w).

; 3455 (s), 2950 (s), 2850 (s), 1720 (s), 1585 (m), 1540 (m), 1455 (m), 1445 (m), 1420 (m), 1310 (w), 1295 (m), 1280 (m), 1260 (m), 1230 (w), 1205 (w), 1100 (w), 1095 (s), 1040 (m), 990 (m), 980 (m), 960 (w), 940 (w), 890 (m), 760 (w), 745 (m), 680 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.25(m,singlets at 0.63, 0.75, 1.07, 1.32), 2.45∼3.0(3H, m), 3.55∼4.15(3H, m), 7.0∼8.60(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.75, 1.07, 1.32), 2.45 to 3.0 (3H, m), 3.55 to 4.15 (3H, m) , 7.0 to 8.60 (4H, m).

원소분석(C₂₈H₄₁O₄N)Elemental Analysis (C ₂₈ H ₄₁ O ₄ N)

실측치(%) : C; 74.93, H; 9.46, O; 13.27Found (%): C; 74.93, H; 9.46, 0; 13.27

[실시예 43]Example 43

2α,3α-디히드록시-20-{1-히드록시-1-(4-메틸-3-피코일)} 메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (4-methyl-3-phycoyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 4-메틸-3-피코일마그네슘브로마이드로부터 실시예 30과 같은 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 4-methyl-3-phycoylmagnesium bromide.

융점 : 182∼186℃Melting Point: 182 ~ 186 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1580(m), 1530(m), 1450(m), 1440(m), 1405(m), 1310(w), 1295(m), 1280(m), 1260(m), 1240(w), 1200(w), 1100(w), 1090(s), 1040(m), 980(w), 960(w), 940(w), 890(m), 760(w), 740(m), 680(w), 540(w).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1580 (m), 1530 (m), 1450 (m), 1440 (m), 1405 (m), 1310 (w), 1295 (m), 1280 (m), 1260 (m), 1240 (w), 1200 (w), 1100 (w), 1090 (s), 1040 (m), 980 (w), 960 (w), 940 (w), 890 (m), 760 (w), 740 (m), 680 (w), 540 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.25(m,singlets at 0.63, 0.75, 1.07, 1.21), 2.40∼3.05(6H, m), 3.58∼4.14(3H, m), 7.0∼8.60(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.75, 1.07, 1.21), 2.40 to 3.05 (6H, m), 3.58 to 4.14 (3H, m) , 7.0 to 8.60 (3H, m).

원소분석(C₂₉H₄₃O₄N)Elemental Analysis (C ₂₉ H ₄₃ O ₄ N)

실측치(%) : C; 75.27, H; 8.48, O; 13.20Found (%): C; 75.27, H; 8.48, 0; 13.20

[실시예 44]Example 44

2α,3α-디히드록시-20-{1-히드록시-1-(6-메틸-3-피코일)}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (6-methyl-3-phycoyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 6-메틸-3-피코일마그네슘브로마이드로부터 실시예 30과 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 6-methyl-3-phycoylmagnesium bromide.

융점 : 186∼188℃Melting Point: 186 ~ 188 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1580(m), 1520(m), 1450(m), 1440(m), 1410(m), 1400(m), 1310(w), 1290(m), 1280(m), 1260(m), 1200(w), 1100(w), 1090(s), 1040(m), 970(w), 935(w), 880(m), 760(w), 720(m), 680(w), 540(w), 525(w).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1580 (m), 1520 (m), 1450 (m), 1440 (m), 1410 (m), 1400 (m), 1310 (w), 1290 (m), 1280 (m), 1260 (m), 1200 (w), 1100 (w), 1090 (s), 1040 (m), 970 (w), 935 (w), 880 (m), 760 (w), 720 (m), 680 (w), 540 (w), 525 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.25(m,singlets at 0.63, 0.75), 2.45∼3.10(6H, m), 3.50∼4.14(3H, m), 7.0∼8.60(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.75), 2.45 to 3.10 (6H, m), 3.50 to 4.14 (3H, m), 7.0 to 8.60 (3H, m).

원소분석(C₂₉H₄₃O₄N)Elemental Analysis (C ₂₉ H ₄₃ O ₄ N)

실측치(%) : C; 74.12, H; 9.78, O; 14.13Found (%): C; 74.12, H; 9.78, 0; 14.13

[실시예 45]Example 45

2α,3α-디히드록시-20-{1-히드록시-1-(4-피코일)}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (4-picoyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 4-피코일마그네슘브로마이드로부터 실시예 30d에서 기술된 방법과 동일한 방법으로 제조하였다.Compound (0.76 g) and 4-phycoylmagnesium bromide were prepared in the same manner as described in Example 30d.

융점 : 174∼177℃Melting Point: 174 ~ 177 ℃

; 3440(s), 2950(s), 2845(s), 1720(s), 1570(m), 1540(m), 1460(m), 1450(m), 1420(m), 1320(w), 1310(w), 1280(m), 1260(m), 1225(w), 1210(w), 1100(w), 1050(s), 1040(m), 1000(w), 980(w), 950(w), 930(w), 880(w), 750(w), 720(m), 685(w), 640(w).

; 3440 (s), 2950 (s), 2845 (s), 1720 (s), 1570 (m), 1540 (m), 1460 (m), 1450 (m), 1420 (m), 1320 (w), 1310 (w), 1280 (m), 1260 (m), 1225 (w), 1210 (w), 1100 (w), 1050 (s), 1040 (m), 1000 (w), 980 (w), 950 (w), 930 (w), 880 (w), 750 (w), 720 (m), 685 (w), 640 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.35(m,singlets at 0.63, 0.72, 0.83, 1.07), 2.45∼3.10(3H, m), 3.55∼4.15(3H, m), 7.0∼8.60(4H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.72, 0.83, 1.07), 2.45 to 3.10 (3H, m), 3.55 to 4.15 (3H, m) , 7.0 to 8.60 (4H, m).

원소분석(C₂₈H₄₁O₄N)Elemental Analysis (C ₂₈ H ₄₁ O ₄ N)

실측치(%) : C; 73.13, H; 8.72, O; 14.38Found (%): C; 73.13, H; 8.72, 0; 14.38

[실시예 46]Example 46

2α,3α-디히드록시-20-{1-히드록시-1-(2-메틸-4-피코일)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2-methyl-4-picoyl) methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-메틸-4-피코일마그네슘브로마이드로부터 실시예 30과 동일한 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 2-Methyl-4-PicoylMagnesium Bromide.

융점 : 185∼187℃Melting Point: 185 ~ 187 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1560(m), 1530(m), 1480(m), 1450(m), 1425(m), 1320(w), 1280(m), 1265(m), 1210(w), 1100(w), 1080(s), 1045(m), 1000(w), 980(m), 950(w), 940(w), 880(w), 760(w), 750(m).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1560 (m), 1530 (m), 1480 (m), 1450 (m), 1425 (m), 1320 (w), 1280 (m), 1265 (m), 1210 (w), 1100 (w), 1080 (s), 1045 (m), 1000 (w), 980 (m), 950 (w), 940 (w), 880 (w), 760 (w), 750 (m).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.63, 0.74), 2.45∼3.10(6H, m), 3.55∼4.12(3H, m), 7.0∼8.60(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.74), 2.45 to 3.10 (6H, m), 3.55 to 4.22 (3H, m), 7.0 to 8.60 (3H, m).

원소분석(C₂₉H₄₃O₄N)Elemental Analysis (C ₂₉ H ₄₃ O ₄ N)

실측치(%) : C; 74.49, H; 9.73, O; 14.27Found (%): C; 74.49, H; 9.73, 0; 14.27

[실시예 47]Example 47

2α,3α-디히드록시-20-{1-히드록시-1-(5-메틸-4-피코일)}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (5-methyl-4-picoyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 5-메틸-4-피코일마그네슘브로마이드로부터 실시예 30에서 서술된 방법과 같은 방법으로 제조하였다.The compound of formula (II) (0.76 g) and 5-methyl-4-phycoylmagnesium bromide were prepared in the same manner as described in Example 30.

융점 : 189∼193℃Melting Point: 189 ~ 193 ℃

; 3450(s), 2960(s), 2850(s), 1720(s), 1570(s), 1540(m), 1445(m), 1460(m), 1335(w), 1320(w), 1270(m), 1260(m), 1220(w), 1995(w), 1100(w), 1080(s), 750(m), 700(w), 680(w).

; 3450 (s), 2960 (s), 2850 (s), 1720 (s), 1570 (s), 1540 (m), 1445 (m), 1460 (m), 1335 (w), 1320 (w), 1270 (m), 1260 (m), 1220 (w), 1995 (w), 1100 (w), 1080 (s), 750 (m), 700 (w), 680 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.56∼2.40(m,singlets at 0.63, 0.75, 0.85), 2.45∼3.05(6H, m), 3.50∼4.15(3H, m), 7.0∼8.60(3H, m)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.56 to 2.40 (m, singlets at 0.63, 0.75, 0.85), 2.45 to 3.05 (6H, m), 3.50 to 4.15 (3H, m), 7.0 -8.60 (3H, m)

원소분석(C₂₉H₄₃O₄N)Elemental Analysis (C ₂₉ H ₄₃ O ₄ N)

실측치(%) : C; 75.31, H; 8.12, O; 14.14Found (%): C; 75.31, H; 8.12, 0; 14.14

[실시예 48]Example 48

2α,3α-디히드록시-20-{(1-히드록시-2-푸라닐)에틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-2-furanyl) ethyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-메틸푸라닐마그네슘브로마이드(0.5ml, 10N 에테르 용액)으로부터 실시예 30에서의 방법과 같은 방법으로 제조하였다.It was prepared by the same method as in Example 30 from Compound (II) (0.76 g) and 2-methylfuranyl magnesium bromide (0.5 ml, 10N ether solution).

융점 : 192∼196℃Melting Point: 192∼196 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1460(m), 1455(m), 1420(m), 1380(m), 1340(w), 1310(w), 1270(m), 1250(w), 1230(w), 1200(w), 1100(w), 1080(s), 1040(m), 1020(m), 990(m), 950(w), 930(w), 880(w), 760(w), 740(w), 710(m).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1460 (m), 1455 (m), 1420 (m), 1380 (m), 1340 (w), 1310 (w), 1270 (m), 1250 (w), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1040 (m), 1020 (m), 990 (m), 950 (w), 930 (w), 880 (w), 760 (w), 740 (w), 710 (m).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m, singlets at 0.65, 0.74, 0.87, 0.89), 2.45∼3.0(3H, m), 3.55∼4.12(3H, m), 5.80∼7.40(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.65, 0.74, 0.87, 0.89), 2.45 to 3.0 (3H, m), 3.55 to 4.12 (3H, m) , 5.80 to 7.40 (3H, m).

원소분석(C₂₇H₄₀O₅)Elemental Analysis (C ₂₇ H ₄₀ O ₅ )

계산치(%) : C; 72.99, H; 9.00, O; 18.00Calculated (%): C; 72.99, H; 9.00, 0; 18.00

실측치(%) : C; 71.27, H; 8.24, O; 17.21Found (%): C; 71.27, H; 8.24, 0; 17.21

[실시예 49]Example 49

2α,3α-디히드록시-20-{(1-히드록시-2-티오페닐)에틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-2-thiophenyl) ethyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-메틸티오페닐마그네슘브로마이드로부터 실시예 30에서의 방법으로 제조하였다.Prepared by the method in Example 30 from compound (II) (0.76 g) and 2-methylthiophenylmagnesium bromide.

융점 : 173∼177℃Melting Point: 173 ~ 177 ℃

; 3455(s), 2955(s), 2850(s), 1720(s), 1570(w), 1460(m), 1450(m), 1420(m), 1380(m), 1340(w), 1310(w), 1270(m), 1240(w), 1200(w), 1080(s), 1040(m), 1020(m), 980(m), 950(w), 930(w), 880(w), 760(w), 750(w), 730(w), 710(m).

; 3455 (s), 2955 (s), 2850 (s), 1720 (s), 1570 (w), 1460 (m), 1450 (m), 1420 (m), 1380 (m), 1340 (w), 1310 (w), 1270 (m), 1240 (w), 1200 (w), 1080 (s), 1040 (m), 1020 (m), 980 (m), 950 (w), 930 (w), 880 (w), 760 (w), 750 (w), 730 (w), 710 (m).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.65, 0.74, 0.86, 0.89), 2.40∼3.0(3H, m), 3.55∼4.20(3H, m), 6.70∼7.30(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.65, 0.74, 0.86, 0.89), 2.40 to 3.0 (3H, m), 3.55 to 4.20 (3H, m) , 6.70 to 7.30 (3H, m).

원소분석(C₂₇H₄₀O₄S)Elemental Analysis (C ₂₇ H ₄₀ O ₄ S)

계산치(%) : C; 70.46, H; 8.69, O; 13.90Calculated (%): C; 70.46, H; 8.69, 0; 13.90

실측치(%) : C; 71.27, H; 9.25, O; 14.51Found (%): C; 71.27, H; 9.25, O; 14.51

[실시예 50]Example 50

2α,3α-디히드록시-20-{(1-히드록시-2-이소옥사졸)에틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20-{(1-hydroxy-2-isoxazole) ethyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 5-메틸이소옥사졸마그네슘 브로마이드로부터 실시예 30과 같은 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 5-methylisoxazole magnesium bromide.

융점 : 181∼184.5℃Melting Point: 181-184.5 ℃

; 3480(s), 2960(s), 2860(s), 1725(s), 1600(w), 1570(m), 1540(m), 1450(m), 1440(m), 1420(m), 1330(w), 1310(w), 1280(m), 1250(m), 1230(w), 1200(w), 1100(w), 1080(s), 1040(m), 1000(w), 980(m), 940(w), 880(w), 740(w).

; 3480 (s), 2960 (s), 2860 (s), 1725 (s), 1600 (w), 1570 (m), 1540 (m), 1450 (m), 1440 (m), 1420 (m), 1330 (w), 1310 (w), 1280 (m), 1250 (m), 1230 (w), 1200 (w), 1100 (w), 1080 (s), 1040 (m), 1000 (w), 980 (m), 940 (w), 880 (w), 740 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.40(m,singlets at 0.63, 0.74, 0.86, 0.95, 1.03), 2.40∼3.00(3H, m), 3.55∼4.15(3H, m), 6.0(1H,s), 8.13(1H,s)NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.40 (m, singlets at 0.63, 0.74, 0.86, 0.95, 1.03), 2.40 to 3.00 (3H, m), 3.55 to 4.15 (3H, m), 6.0 (1H, s), 8.13 (1H, s)

원소분석(C₂₆H₃₉O₅N)Elemental Analysis (C ₂₆ H ₃₉ O ₅ N)

계산치(%) : C; 70.14, H; 8.76, O; 17.96Calculated (%): C; 70.14, H; 8.76, 0; 17.96

실측치(%) : C; 71.41, H; 8.47, O; 18.25Found (%): C; 71.41, H; 8.47, 0; 18.25

[실시예 51]Example 51

2α,3α-디히드록시-20-{1-히드록시-1-(2,3-디메틸벤질)메틸}-5α-프레그난-6-온의 제조.Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2,3-dimethylbenzyl) methyl} -5α-pregnan-6-one.

일반식(II) 화합물(0.76g)과 2,3-디메틸벤질마그네슘브로마이드로부터 실시예 30에서와 같은 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 2,3-dimethylbenzyl magnesium bromide.

융점 : 214∼216℃Melting Point: 214 ~ 216 ℃

; 3450(s), 2950(s), 2860(s), 1720(s), 1600(w), 1460(m), 1450(m), 1420(m), 1380(m), 1340(w), 1310(w), 1280(m), 1250(w), 1225(w), 1205(w), 1100(w), 1090(s), 1045(m), 1015(m), 995(m), 950(w), 940(w), 880(w), 760(w), 745(w), 710(m), 680(w).

; 3450 (s), 2950 (s), 2860 (s), 1720 (s), 1600 (w), 1460 (m), 1450 (m), 1420 (m), 1380 (m), 1340 (w), 1310 (w), 1280 (m), 1250 (w), 1225 (w), 1205 (w), 1100 (w), 1090 (s), 1045 (m), 1015 (m), 995 (m), 950 (w), 940 (w), 880 (w), 760 (w), 745 (w), 710 (m), 680 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.20(m,singlets at 0.63, 0.74), 2.30(6H,s), 2.50∼2.82(3H, m), 3.58∼4.10(3H, m), 7.14(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.20 (m, singlets at 0.63, 0.74), 2.30 (6H, s), 2.50 to 2.82 (3H, m), 3.58 to 4.10 (3H , m), 7.14 (3H, m).

원소분석(C₃₁H₄₆O₄)Elemental Analysis (C ₃₁ H ₄₆ O ₄ )

실측치(%) : C; 78.32, H; 9.94, O; 13.29Found (%): C; 78.32, H; 9.94, 0; 13.29

[실시예 52]Example 52

2α,3α-디히드록시-20-{1-히드록시-1-(2,5-디메틸벤질)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2,5-dimethylbenzyl) methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2,5-디메틸벤질마그네슘브로마이드로부터 실시예 30과 같은 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and 2,5-dimethylbenzyl magnesium bromide.

융점 : 217∼219℃Melting Point: 217 ~ 219 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1466(m), 1450(m), 1420(m), 1380(m), 1345(w), 1310(w), 1275(m), 1250(w), 1220(w), 1200(w), 1100(w), 1080(s), 1050(m), 1020(m), 1000(m), 950(w), 940(w), 880(w), 760(w), 740(w), 710(w), 680(w), 645(w).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1466 (m), 1450 (m), 1420 (m), 1380 (m), 1345 (w), 1310 (w), 1275 (m), 1250 (w), 1220 (w), 1200 (w), 1100 (w), 1080 (s), 1050 (m), 1020 (m), 1000 (m), 950 (w), 940 (w), 880 (w), 760 (w), 740 (w), 710 (w), 680 (w), 645 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.15(m,singlets at 0.63, 0.75, 0.84, 0.97), 2.30(6H, m), 2.50∼2.85(3H, m), 3.58∼4.15(3H, m), 7.13(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.15 (m, singlets at 0.63, 0.75, 0.84, 0.97), 2.30 (6H, m), 2.50 to 2.85 (3H, m), 3.58 -4.15 (3H, m), 7.13 (3H, m).

원소분석(C₃₁H₄₆O₄)Elemental Analysis (C ₃₁ H ₄₆ O ₄ )

실측치(%) : C; 77.49, H; 9.14, O; 13.82Found (%): C; 77.49, H; 9.14, O; 13.82

[실시예 53]Example 53

2α,3α-디히드록시-20-{1-히드록시-1-(2-메틸-6-에틸벤질)}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2-methyl-6-ethylbenzyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-메틸-6-에틸벤질마그네슘브로마이드로부터 실시예 30에서와 같은 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 30 from compound (0.76 g) and 2-methyl-6-ethylbenzyl magnesium bromide.

융점 : 217∼219℃Melting Point: 217 ~ 219 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1465(m), 1450(m), 1430(m), 1380(m), 1340(w), 1310(w), 1270(m), 1250(w), 1210(w), 1200(w), 1100(w), 1070(s), 1050(m), 1020(m), 1000(m), 950(w), 935(w), 870(w), 765(w), 740(w), 710(w), 675(w), 640(w), 625(w).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1465 (m), 1450 (m), 1430 (m), 1380 (m), 1340 (w), 1310 (w), 1270 (m), 1250 (w), 1210 (w), 1200 (w), 1100 (w), 1070 (s), 1050 (m), 1020 (m), 1000 (m), 950 (w), 935 (w), 870 (w), 765 (w), 740 (w), 710 (w), 675 (w), 640 (w), 625 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.15(m,singlets at 0.63, 0.73, 1.10, 1.20, 1.45, 1.62), 2.30(3H,s), 2.40∼2.80(5H, m), 3.55∼4.15(3H, m), 7.12(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.15 (m, singlets at 0.63, 0.73, 1.10, 1.20, 1.45, 1.62), 2.30 (3H, s), 2.40 to 2.80 (5H, m), 3.55 to 4.15 (3H, m), 7.12 (3H, m).

원소분석(C₃₂H₄₈O₄)Elemental Analysis (C ₃₂ H ₄₈ O ₄ )

실측치(%) : C; 76.92, H; 9.32, O; 13.18Found (%): C; 76.92, H; 9.32, O; 13.18

[실시예 54]Example 54

2α,3α-디히드록시-20-{1-히드록시-1-(2-메틸-3-에틸벤질)}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2-methyl-3-ethylbenzyl)}-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 (2-메틸-3-에틸)벤질마그네슘브로마이드로부터 실시예 30에서와 같은 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and (2-methyl-3-ethyl) benzyl magnesium bromide.

융점 : 214∼218℃Melting Point: 214 ~ 218 ℃

; 3500(s), 2950(s), 2860(s), 1720(s), 1600(w), 1460(m), 1450(m), 1430(m), 1380(m), 1335(w), 1310(w), 1270(m), 1250(w), 1210(w), 1200(w), 1105(w), 1070(s), 1050(m), 1000(m), 950(w), 935(w), 870(w), 765(w), 740(w), 715(w), 675(w), 640(w), 620(w).

; 3500 (s), 2950 (s), 2860 (s), 1720 (s), 1600 (w), 1460 (m), 1450 (m), 1430 (m), 1380 (m), 1335 (w), 1310 (w), 1270 (m), 1250 (w), 1210 (w), 1200 (w), 1105 (w), 1070 (s), 1050 (m), 1000 (m), 950 (w), 935 (w), 870 (w), 765 (w), 740 (w), 715 (w), 675 (w), 640 (w), 620 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.20(m,singlets at 0.63, 0.73), 2.30(3H,s), 2.40∼2.80(5H, m), 3.55∼4.20(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.20 (m, singlets at 0.63, 0.73), 2.30 (3H, s), 2.40 to 2.80 (5H, m), 3.55 to 4.20 (3H , m).

원소분석(C₃₂H₄₈O₄)Elemental Analysis (C ₃₂ H ₄₈ O ₄ )

실측치(%) : C; 78.43, H; 9.83, O; 12.19Found (%): C; 78.43, H; 9.83, 0; 12.19

[실시예 55]Example 55

2α,3α-디히드록시-20-{1-히드록시-1-(3-메틸-4-이소프로필)벤질}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (3-methyl-4-isopropyl) benzyl} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 (3-메틸-4-이소프로필)벤질마그네슘브로마이드로부터 실시예 30에서와 같은 방법으로 제조하였다.It was prepared in the same manner as in Example 30 from Compound (II) (0.76 g) and (3-methyl-4-isopropyl) benzyl magnesium bromide.

융점 : 242∼249℃Melting Point: 242 ~ 249 ℃

; 3450(s), 2950(s), 2870(s), 1720(s), 1520(w), 1450(m), 1440(m), 1430(w), 1380(m), 1330(w), 1315(w), 1280(w), 1260(w), 1230(w), 1200(w), 1100(w), 1060(w), 1040(w), 1000(m), 970(m), 920(w), 860(w), 805(w), 680(w), 640(w).

; 3450 (s), 2950 (s), 2870 (s), 1720 (s), 1520 (w), 1450 (m), 1440 (m), 1430 (w), 1380 (m), 1330 (w), 1315 (w), 1280 (w), 1260 (w), 1230 (w), 1200 (w), 1100 (w), 1060 (w), 1040 (w), 1000 (m), 970 (m), 920 (w), 860 (w), 805 (w), 680 (w), 640 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.45(m,singlets at 0.64, 0.73, 1.26, 1.47), 2.30(3H,s), 2.50∼3.0(4H, m), 3.55∼4.15(3H, m), 7.10(3H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.45 (m, singlets at 0.64, 0.73, 1.26, 1.47), 2.30 (3H, s), 2.50 to 3.0 (4H, m), 3.55 -4.15 (3H, m), 7.10 (3H, s).

원소분석(C₃₃H₅₀O₄)Elemental Analysis (C ₃₃ H ₅₀ O ₄ )

계산치(%) : C; 77.67, H; 9.80, O; 12.53Calculated (%): C; 77.67, H; 9.80, O; 12.53

실측치(%) : C; 77.12, H; 9.42, O; 11.43Found (%): C; 77.12, H; 9.42, O; 11.43

[실시예 56]Example 56

2α,3α-디히드록시-20-{1-히드록시-1-(2-메틸-4-이소프로필벤질)}메틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2-methyl-4-isopropylbenzyl)} methyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 (2-메틸-4-이소프로필)벤질마그네슘브로마이드로부터 실시예 30에서의 방법과 동일한 방법으로 제조하였다.Compound (0.7) was prepared in the same manner as in Example 30 from compound (0.76 g) and (2-methyl-4-isopropyl) benzyl magnesium bromide.

융점 : 232∼236℃Melting Point: 232 ~ 236 ℃

; 3450(s), 2950(s), 2840(s), 1720(s), 1460(m), 1450(m), 1430(m), 1380(m), 1340(w), 1310(w), 1270(s), 1250(w), 1210(w), 1200(w), 1100(w), 1050(s), 1045(m), 1000(m), 945(w), 935(w), 860(w), 760(w), 740(w), 705(w), 640(w).

; 3450 (s), 2950 (s), 2840 (s), 1720 (s), 1460 (m), 1450 (m), 1430 (m), 1380 (m), 1340 (w), 1310 (w), 1270 (s), 1250 (w), 1210 (w), 1200 (w), 1100 (w), 1050 (s), 1045 (m), 1000 (m), 945 (w), 935 (w), 860 (w), 760 (w), 740 (w), 705 (w), 640 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.25(m,singlets at 0.63, 0.75, 0.83, 0.87), 2.30(3H, m), 2.40∼2.75(4H, m), 3.55∼4.20(3H, m), 7.05(3H, m).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.25 (m, singlets at 0.63, 0.75, 0.83, 0.87), 2.30 (3H, m), 2.40 to 2.75 (4H, m), 3.55 4.20 (3H, m), 7.05 (3H, m).

원소분석(C₃₃H₅₀O₄)Elemental Analysis (C ₃₃ H ₅₀ O ₄ )

실측치(%) : C; 78.43, H; 9.92, O; 11.87Found (%): C; 78.43, H; 9.92, O; 11.87

[실시예 57]Example 57

2α,3α-디히드록시-20-{1-히드록시-1-(2,3,4-트리메틸벤질)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2,3,4-trimethylbenzyl) methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2,3,4-트리메틸벤질마그네슘브로마이드로부터 실시예 30에서와 같은 방법으로 제조하였다.Compound (II) was prepared in the same manner as in Example 30 from compound (0.76 g) and 2,3,4-trimethylbenzyl magnesium bromide.

융점 : 259∼261℃Melting Point: 259 ~ 261 ℃

; 3450(s), 2950(s), 2850(s), 1720(s), 1600(w), 1460(m), 1440(m), 1430(m), 1380(m), 1340(w), 1310(w), 1270(m), 1250(w), 1210(w), 1200(w), 1105(w), 1060(s), 1050(m), 1020(m), 1000(m), 950(w), 930(w), 875(w), 760(w), 740(w), 710(w), 670(w), 640(w), 630(w).

; 3450 (s), 2950 (s), 2850 (s), 1720 (s), 1600 (w), 1460 (m), 1440 (m), 1430 (m), 1380 (m), 1340 (w), 1310 (w), 1270 (m), 1250 (w), 1210 (w), 1200 (w), 1105 (w), 1060 (s), 1050 (m), 1020 (m), 1000 (m), 950 (w), 930 (w), 875 (w), 760 (w), 740 (w), 710 (w), 670 (w), 640 (w), 630 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.20(m,singlets at 0.65, 0.73, 1.10, 1.20), 2.30(9H,s), 2.40∼2.80(3H, m), 3.55∼4.15(3H, m), 7.02(2H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.20 (m, singlets at 0.65, 0.73, 1.10, 1.20), 2.30 (9H, s), 2.40 to 2.80 (3H, m), 3.55 -4.15 (3H, m), 7.02 (2H, s).

원소분석(C₃₂H₄₈O₄)Elemental Analysis (C ₃₂ H ₄₈ O ₄ )

실측치(%) : C; 78.12, H; 10.12, O; 13.14Found (%): C; 78.12, H; 10.12, O; 13.14

[실시예 58]Example 58

2α,3α-디히드록시-20-{1-히드록시-1-(2,3,5-트리메틸벤질)메틸}-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- {1-hydroxy-1- (2,3,5-trimethylbenzyl) methyl} -5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2,3,5-트리메틸벤질마그네슘브로마이드로부터 실시예 30에서의 방법과 같이 제조하였다.Prepared according to the method of Example 30 from compound (II) (0.76 g) and 2,3,5-trimethylbenzyl magnesium bromide.

융점 : 242∼245℃Melting Point: 242 ~ 245 ℃

; 3480(s), 2955(s), 2850(s), 1725(s), 1600(w), 1460(m), 1430(m), 1380(m), 1340(w), 1310(w), 1270(m), 1250(w), 1201(w), 1200(2), 1100(w), 1060(s), 1050(m), 1020(m), 1000(m), 950(w), 920(w), 870(w), 760(w), 740(w), 710(w), 645(w).

; 3480 (s), 2955 (s), 2850 (s), 1725 (s), 1600 (w), 1460 (m), 1430 (m), 1380 (m), 1340 (w), 1310 (w), 1270 (m), 1250 (w), 1201 (w), 1200 (2), 1100 (w), 1060 (s), 1050 (m), 1020 (m), 1000 (m), 950 (w), 920 (w), 870 (w), 760 (w), 740 (w), 710 (w), 645 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.20(m,singlets at 0.65, 0.74), 2.30(9H,s), 2.40∼2.80(3H, m), 3.52∼4.13(3H, m), 6.98(2H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.20 (m, singlets at 0.65, 0.74), 2.30 (9H, s), 2.40 to 2.80 (3H, m), 3.52 to 4.13 (3H m), 6.98 (2H, s).

원소분석(C₃₂H₄₈O₄)Elemental Analysis (C ₃₂ H ₄₈ O ₄ )

계산치(%) : C; 78.44, H; 9.67, O; 12.89Calculated (%): C; 78.44, H; 9.67, 0; 12.89

실측치(%) : C; 78.12, H; 9.38, O; 11.92Found (%): C; 78.12, H; 9.38, 0; 11.92

[실시예 59]Example 59

2α,3α-디히드록시-20-[1-히드록시-3-메틸-3-페닐]프로필-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- [1-hydroxy-3-methyl-3-phenyl] propyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 2-메틸-2-페닐에틸마그네슘브로마이드에서 실시예 30에서의 방법과 방법으로 제조하였다.Prepared by the method and method of Example 30 in General Formula (II) Compound (0.76 g) and 2-methyl-2-phenylethylmagnesium bromide.

융점 : 247∼251℃Melting Point: 247 ~ 251 ℃

; 3450(s), 2950(s), 2850(s), 1725(s), 1600(w), 1505(w), 1475(w), 1460(m), 1430(m), 1420(m), 1395(m), 1390(m), 1340(w), 1330(w), 1310(m), 1295(w), 1275(m), 1235(m), 1190(m), 1150(w), 1145(w), 1100(m), 1075(m), 1040(m), 1030(m), 1000(m), 975(w), 965(m), 940(w), 920(m), 890(w), 880(w), 860(w), 825(w), 780(w), 720(m), 680(m), 640(w), 595(w), 570(w), 550(w).

; 3450 (s), 2950 (s), 2850 (s), 1725 (s), 1600 (w), 1505 (w), 1475 (w), 1460 (m), 1430 (m), 1420 (m), 1395 (m), 1390 (m), 1340 (w), 1330 (w), 1310 (m), 1295 (w), 1275 (m), 1235 (m), 1190 (m), 1150 (w), 1145 (w), 1100 (m), 1075 (m), 1040 (m), 1030 (m), 1000 (m), 975 (w), 965 (m), 940 (w), 920 (m), 890 (w), 880 (w), 860 (w), 825 (w), 780 (w), 720 (m), 680 (m), 640 (w), 595 (w), 570 (w), 550 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.60∼2.40(m,singlets at 0.66, 0.74, 1.67), 2.50∼2.83(2H, m), 3.55∼4.15(3H, m), 7.15(5H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.60 to 2.40 (m, singlets at 0.66, 0.74, 1.67), 2.50 to 2.83 (2H, m), 3.55 to 4.15 (3H, m), 7.15 (5H, s).

원소분석(C₃₁H₄₆O₄)Elemental Analysis (C ₃₁ H ₄₆ O ₄ )

실측치(%) : C; 76.84, H; 9.13, O; 14.13Found (%): C; 76.84, H; 9.13, O; 14.13

[실시예 60]Example 60

2α,3α-디히드록시-20-[1-히드록시-2-티오페녹시]에틸-5α-프레그난-6-온의 제조Preparation of 2α, 3α-dihydroxy-20- [1-hydroxy-2-thiophenoxy] ethyl-5α-pregnan-6-one

일반식(II) 화합물(0.76g)과 티오페녹시메틸 마그네슘클로라이드로부터 실시예 30에서의 방법과 동일하게 제조되었다.It was prepared in the same manner as in Example 30 from compound (II) (0.76 g) and thiophenoxymethyl magnesium chloride.

융점 : 182∼185℃Melting Point: 182 ~ 185 ℃

; 3450(s), 2950(s), 2860(s), 1750(s), 1600(w), 1460(m), 1455(m), 1420(m), 1380(m), 1345(w), 1310(w), 1275(m), 1265(w), 1230(w), 1200(w), 1100(w), 1090(s), 1040(m), 1020(m), 990(m), 950(w), 940(w), 880(w), 760(w), 740(w), 700(w), 680(w), 645(w).

; 3450 (s), 2950 (s), 2860 (s), 1750 (s), 1600 (w), 1460 (m), 1455 (m), 1420 (m), 1380 (m), 1345 (w), 1310 (w), 1275 (m), 1265 (w), 1230 (w), 1200 (w), 1100 (w), 1090 (s), 1040 (m), 1020 (m), 990 (m), 950 (w), 940 (w), 880 (w), 760 (w), 740 (w), 700 (w), 680 (w), 645 (w).

NMR(H, 80MHz, CDCl₃/TMS)δ(ppm) : 0.55∼2.35(m,singlets at 0.63, 0.74, 4), 2.45∼3.0(1H, m), 3.55∼4.25(5H, m), 7.15(5H,s).NMR (H, 80 MHz, CDCl ₃ / TMS) δ (ppm): 0.55 to 2.35 (m, singlets at 0.63, 0.74, 4), 2.45 to 3.0 (1H, m), 3.55 to 4.25 (5H, m), 7.15 (5H, s).

원소분석(C₂₉H₄₂O₄S)Elemental Analysis (C ₂₉ H ₄₂ O ₄ S)

계산치(%) : C; 71.62, H; 8.64, O; 13.15Calculated (%): C; 71.62, H; 8.64, O; 13.15

실측치(%) : C; 72.13, H; 8.72, O; 13.84Found (%): C; 72.13, H; 8.72, 0; 13.84

[시험방법][Test Methods]

상기 실시예에서 제조한 브라시노라이드 유사체의 생물학적 활성시험은 벼의 유묘의 라미나조인트의 굴곡 각도를 알아보는 방법을 사용하였다. 이는 극히 낮은 농도에서도 브라시노라이드 유사체의 활성을 검정할 수 있는 극히 효과적인 방법이다[참조 : K.Wada,S.Marumo,N.Ikekawa,M.Morisaki 및 K.Mori,Plant and Cell Physiology, 22, 323(1981)]. 벼(풍산벼, Orizasativa.L.cv.Pungsan)를 발아시킨후, 암실에서 8일간 키운후에 제2절간의 조인트를 2cm길이로 잘라서, 이를 하루동안 암실에서 증류수에 띄워 놓은 다음, 균일한 조인트를 골라 약제(1%아세톤, 1%트윈으로 용액화)로 처리한 다음 2일간 암실에서 띄워 놓는다. 이를 꺼내 녹색광하에서 그의 굴곡 각도를 측정한다.The biological activity test of the brassinolide analogue prepared in the above example was used to determine the bending angle of the lamina joint of rice seedlings. This is an extremely effective method for assaying the activity of brassinolide analogs even at very low concentrations. K. Wada, S. Marumo, N. Ikekawa, M. Morisaki and K. Mori, Plant and Cell Physiology, 22, 323 (1981). After germinating rice (Pungsan rice, Orizasativa.L.cv.Pungsan), grow it in a dark room for 8 days, cut the joints of section 2 into 2cm lengths, float it in distilled water in the dark room for a day, and then put a uniform joint Pick and treat with 1% acetone, 1% twin, then leave in the dark for 2 days. This is taken out and its bending angle under green light is measured.

생물 실험의 결과를 하기표에 나타냈다.The results of the biological experiments are shown in the table below.

*주)^*C는 대조구의 굴곡각도를 나타냄.* Note) ^* C represents the bending angle of the control.

본 발명에 따라 제조된 신규 브라시노라이드 유사체는 상기 표에서 나타난 바와 같이, 대조구에 비해 강력한 생리활성을 갖고 있음을 나타 냈다.The novel brassinolide analogue prepared according to the present invention, as shown in the table, showed that it has a strong physiological activity compared to the control.

따라서 본원의 목적물은 연중 일조량이 적은 지방에서 확기적으로 농업에 이용할 수 있으며, 온대, 열대 지방에서는 종래보다 2~3모작 경작이 충분한 효과를 나타내며 특히 경제작물의 영농을 성취할 수 있는 가능성이 있는 효과를 부여한다.Therefore, the object of the present application can be used for agriculture in the region of low sunshine year-round, and in the temperate and tropical regions, two to three crops cultivation effect is more effective than before, and there is a possibility of achieving agricultural crops of economic crops. Give effect.

Claims

하기 일반식(II)의 6,6-에틸렌-2α,3α-이소프로필렌-디옥시-5α-프레그난-20S-카르복스 알데히드를 유기금속 화합물과 반응시켜 하기 일반식(III)의 화합물을 얻은 후, 이의 보호기를 제거하여 신규의 하기 일반식(I)의 브라시노 유사체의 제조방법.6,6-ethylene-2α, 3α-isopropylene-dioxy-5α-pregnane-20S-carboxaldehyde of the following general formula (II) was reacted with an organometallic compound to obtain a compound of the following general formula (III) Thereafter, its protecting group is removed to prepare a novel brassino analog of general formula (I) below.

상기식에서, R은 탄소수 1∼10의 지방족 또는 시클로기, 1∼3개의 치환체(여기서 치환체는 저급알킬기, 저급알케닐기임)를 가져도 좋은 방향족기, 1∼3개의 치환체(여기서 치환체는 저급알킬기, 저급알케닐기임)를 가져도 좋은 복소환기를 나타내며, 탄소 22위치와 R 사이에 0∼3개의 탄소수를 가질 수 있다.Wherein R is an aliphatic or cyclo group having 1 to 10 carbon atoms, an aromatic group which may have 1 to 3 substituents (where the substituents are lower alkyl groups and lower alkenyl groups), and 1 to 3 substituents (where the substituents are lower alkyl groups) And a lower alkenyl group), and may have 0 to 3 carbon atoms between the carbon 22 position and R.