JPS6412275B2 - - Google Patents
Info
- Publication number
- JPS6412275B2 JPS6412275B2 JP3286881A JP3286881A JPS6412275B2 JP S6412275 B2 JPS6412275 B2 JP S6412275B2 JP 3286881 A JP3286881 A JP 3286881A JP 3286881 A JP3286881 A JP 3286881A JP S6412275 B2 JPS6412275 B2 JP S6412275B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- present
- boiling point
- elemental analysis
- oxabicyclo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- KKVBULDFFNFYHJ-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]octan-7-one Chemical class C1C2C(=O)OC1CCC2 KKVBULDFFNFYHJ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000003266 anti-allergic effect Effects 0.000 description 3
- 230000003356 anti-rheumatic effect Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 2-octanone Chemical compound CCCCCCC(C)=O ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 0.000 description 1
- SAHAVHUPPLEKKY-UHFFFAOYSA-N 4-oxabicyclo[3.2.1]octan-6-one Chemical class C1C2C(=O)CC1CCO2 SAHAVHUPPLEKKY-UHFFFAOYSA-N 0.000 description 1
- 241000234282 Allium Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 1
- UPRXAOPZPSAYHF-UHFFFAOYSA-N lithium;cyclohexyl(propan-2-yl)azanide Chemical compound CC(C)N([Li])C1CCCCC1 UPRXAOPZPSAYHF-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は一般式（）
（式中、ＲはC2〜C10の直鎖アルキル基又は分枝
アルキル基を意味する）で表わされる新規な６−
オキサビシクロ〔３，２，１〕オクタン−７−オ
ン誘導体に関するものである。[Detailed Description of the Invention] The present invention relates to the general formula () A novel 6-
This invention relates to oxabicyclo[3,2,1]octan-7-one derivatives.
本発明の化合物は文献未載の新規化合物であ
り、抗腫瘍作用、抗アレルギー作用、肝機能改善
作用、抗リウマチ作用等の薬理作用を有し医薬品
として非常に有用な化合物である。 The compound of the present invention is a novel compound that has not been described in any literature, and has pharmacological effects such as antitumor activity, antiallergic effect, liver function improving effect, and antirheumatic effect, and is a very useful compound as a pharmaceutical.
又、本発明の化合物は抗腫瘍作用、抗アレルギ
ー作用、肝機能改善作用、抗リウマチ作用等の薬
理作用を有し医薬品として有用な化合物であると
して別に本願出願人が特許を受けるべく出願中の
化合物を合成する上での中間体としても非常に有
用な化合物である。 The compound of the present invention has pharmacological effects such as anti-tumor activity, anti-allergic effect, liver function improving effect, and anti-rheumatic effect, and is a useful compound as a pharmaceutical. It is also a very useful compound as an intermediate in the synthesis of other compounds.
従来、抗腫瘍剤としては一般にアルキル化剤、
代謝拮抗剤等が臨床上用いられているが、概して
副作用か強くその使用が制限されているのが現状
である。そこで本発明者等は副作用の弱い新規な
抗腫瘍活性化合物を求め鋭意研究を重ねた結果、
一般式（）で表わされる新規化合物の合成に成
功し、薬理作用について種々検討したところ、こ
れらの化合物が顕著な抗腫瘍作用、抗アレルギー
作用、肝機能改善作用、抗リウマチ作用等の薬理
作用を有し、且つ副作用か皆無に等しいことを見
出し本発明を完成したのである。 Conventionally, antitumor agents generally include alkylating agents,
Although anti-metabolites and the like are used clinically, their use is generally restricted due to side effects. Therefore, the present inventors conducted extensive research in search of a new antitumor active compound with weak side effects, and as a result,
After successfully synthesizing new compounds represented by the general formula () and conducting various studies on their pharmacological effects, we found that these compounds have remarkable pharmacological effects such as anti-tumor, anti-allergic, liver function-improving, and anti-rheumatic effects. The present invention was completed based on the discovery that the present invention has no side effects and has virtually no side effects.
次に本発明の製造法について説明するが、これ
は一例にすきす勿論他の化学的類似方法によつて
も製造できるものである。 Next, the manufacturing method of the present invention will be explained, but this is just one example, and it can also be manufactured by other chemically similar methods.
製造法Ａ
但し、式中ＲはC2〜C10の直鎖アルキル基又は
分枝アルキル基を意味する。Manufacturing method A However, in the formula, R means a C2 to C10 straight chain alkyl group or a branched alkyl group.
製造法Ｂ
但し、式中Ｒは前記と同じ意味を有し、Ｘはハ
ロゲン原子を意味する。Manufacturing method B However, in the formula, R has the same meaning as above, and X means a halogen atom.
製造法Ｃ 但し、式中Ｒは前記と同じ意味を表わす。Manufacturing method C However, R in the formula has the same meaning as above.
尚、前記製造法Ａ及びＣの出発物質である一般
式（）及び（）で表わされる化合物はそれぞ
れ本願出願人が特許を受けるべく本願と並行して
出願中の特許出願に記載の方法により合成すれば
よい。 In addition, the compounds represented by the general formulas () and (), which are the starting materials of the above-mentioned production methods A and C, are synthesized by the method described in the patent application that is being filed in parallel with the present application by the applicant. do it.
又、製造法Ｂの出発物質である化合物（）の
合成は例えばクラーク（M.F.Clarke）等のジヤ
ーナル・オブ・ザ・ケミカル・ソサエテイー
（Journalof the Chemical Society）2111（′50）
に準じて行なえばよい。 The synthesis of compound (), which is the starting material for production method B, is described in, for example, Journal of the Chemical Society 2111 ('50) by MFC Clarke et al.
You can do it according to.
前記製造法について具体的に説明すると、製造
法Ａは一般式（）で表わされる化合物を110〜
150℃にて単に加熱すればよい。 To specifically explain the above manufacturing method, manufacturing method A is a compound represented by the general formula () with 110 to
Simply heat at 150°C.
製造法Ｂは窒素気流中にて化合物（）を塩基
（例えばｎ−ブチルリチウム、リチウムジイソプ
ロビルアミド、リテウムシクロヘキシルイソプロ
ピルアミド、リチウム２、２、６、６−テトラメ
チルピペリジド、リチウムジシクロヘキシルアミ
ド等）の存在下に不活性溶媒（例えばジエチルエ
ーテル、テトラヒドロフラン等）中、一般式
（）で表わされるアルキルハライドと反応させ
ればよい。 Production method B involves adding the compound () to a base (e.g. n-butyllithium, lithium diisopropylamide, lithium cyclohexylisopropylamide, lithium 2,2,6,6-tetramethylpiperidide, lithium dicyclohexyl) in a nitrogen stream. amide, etc.) in an inert solvent (for example, diethyl ether, tetrahydrofuran, etc.) with an alkyl halide represented by the general formula ().
製造法Ｃは一般式（）で表わされる化合物を
酸（例えば硫酸、トルエンスルホン酸、三沸化ホ
ウ素等）の存在下、不活性溶媒（例えばジクロル
メタン、クロロホルム、ジエチルエーテル等）中
にて反応させればよい。 Production method C involves reacting a compound represented by the general formula () in an inert solvent (e.g. dichloromethane, chloroform, diethyl ether, etc.) in the presence of an acid (e.g. sulfuric acid, toluenesulfonic acid, boron trifluoride, etc.). That's fine.
以下に実施例を示し本発明を更に具体的に説明
する。 EXAMPLES The present invention will be explained in more detail with reference to Examples below.
実施例 １
シス−４−ヒドロキシ−１−イソペンチルシク
ロヘキサンカルボン酸13ｇを130℃にて１時間加
熱した。反応終了後、減圧蒸留に付すと無色油状
の１−イソペンチル−６−オキサビシクロ〔３，
２，１〕オクタン−７−オン10.3ｇを得た。Example 1 13 g of cis-4-hydroxy-1-isopentylcyclohexanecarboxylic acid was heated at 130°C for 1 hour. After the reaction, distillation under reduced pressure yields a colorless oily 1-isopentyl-6-oxabicyclo[3,
10.3 g of 2,1]octan-7-one was obtained.
この物質の沸点及び元素分析値は次に通りであ
つた。 The boiling point and elemental analysis values of this substance were as follows.
沸 点 118〜124℃／４mmHg
元素分析値 C12H20O2
理 論 値 Ｃ：73.43H：10.27
実 測 値 Ｃ：73.51H：10.21
実施例 ２
ジイソプロピルアミン20.2ｇとテトラヒドロフ
ラン300mlの混液を−15℃に冷却し、15％ｎ−ブ
チルリチウムのヘキサン溶液150mlを窒素気流中
徐々に滴下した。滴下後40分間−15℃にて撹拌
し、次いで６−オキサビシクロ〔３，２，１〕オ
クタン−７−オン23.2ｇを加え、更に−10〜０℃
にてｎ−ヘキシルプロミド33ｇを加えて２時間反
応させた。反応終了後、飽和塩化アンモニウム水
溶液を加え溶媒を留去した。残渣にエーテルを加
え水洗、脱水後エーテルを留去し、シリカゲル・
イソプロピルエーテルカラムクロマトグラフイー
に付して精製し減圧蒸留すると無色油状の１−ｎ
−ヘキシル−６−オキサビシクロ〔３，２，１〕
オクタン−７−オン5.2ｇを得た。 Boiling point 118-124℃/4mmHg Elemental analysis value C 12 H 20 O 2 Theoretical value C: 73.43H: 10.27 Actual value C: 73.51H: 10.21 Example 2 A mixture of 20.2 g of diisopropylamine and 300 ml of tetrahydrofuran was heated to -15 The mixture was cooled to 0.degree. C., and 150 ml of a 15% hexane solution of n-butyllithium was gradually added dropwise in a nitrogen stream. After dropping, stir at -15℃ for 40 minutes, then add 23.2g of 6-oxabicyclo[3,2,1]octan-7-one, and then stir at -10 to 0℃.
33 g of n-hexyl bromide was added thereto and reacted for 2 hours. After the reaction was completed, a saturated aqueous ammonium chloride solution was added and the solvent was distilled off. Ether was added to the residue, washed with water, dehydrated, the ether was distilled off, and silica gel
Purification by isopropyl ether column chromatography and distillation under reduced pressure yields 1-n as a colorless oil.
-hexyl-6-oxabicyclo[3,2,1]
5.2 g of octan-7-one was obtained.
この物質の沸点及び元素分析値は次の通りであ
つた。 The boiling point and elemental analysis values of this substance were as follows.
沸 点 131〜135℃／4.5mmHg
元素分析値 C13H22O2
理 論 値 Ｃ：74.24H：10.54
実 測 例 Ｃ：74.17H：10.58
実施例 ３
１−ｎ−ブチル−３−シクロヘキセン−１−カ
ルボン酸18.2ｇをクロロホルム150mlに溶解し、
濃硫酸10mlを氷冷下撹拌しながら徐々に滴下し
た。室温にて６時間反応させた後炭酸水素ナトリ
ウムを加えて硫酸を中和した。反応混合物に水を
加えクロロホルム層を水洗、脱水し溶媒を留去し
て残渣を減圧蒸留に付すと無色油状の１−ｎ−ブ
チル−６−オキサビシクロ〔３，２，１〕オクタ
ン−７−オン16.3ｇを得た。 Boiling point 131-135℃/4.5mmHg Elemental analysis value C 13 H 22 O 2 Theoretical value C: 74.24H: 10.54 Actual measurement example C: 74.17H: 10.58 Example 3 1-n-butyl-3-cyclohexene-1 -Dissolve 18.2g of carboxylic acid in 150ml of chloroform,
10 ml of concentrated sulfuric acid was gradually added dropwise while stirring under ice cooling. After reacting at room temperature for 6 hours, sodium hydrogen carbonate was added to neutralize the sulfuric acid. Water was added to the reaction mixture, the chloroform layer was washed with water, dehydrated, the solvent was distilled off, and the residue was subjected to vacuum distillation to yield 1-n-butyl-6-oxabicyclo[3,2,1]octane-7- as a colorless oil. 16.3 g of onion was obtained.
この物質の沸点及び元素分析値は次の通りであ
つた。 The boiling point and elemental analysis values of this substance were as follows.
沸 点 101〜107℃／3.5mmHg 元素分析値 C11H18O2 理 論 値 Ｃ：72.49H：9.96 実 測 値 Ｃ：72.40H：10.01 Boiling point 101-107℃/3.5mmHg Elemental analysis value C 11 H 18 O 2 Theoretical value C: 72.49H: 9.96 Actual value C: 72.40H: 10.01
Claims (1)
アルキル基を意味する）で表わされる新規な６−
オキサビシクロ〔３，２，１〕オクタン−７−オ
ン誘導体。[Claims] 1. General formula A novel 6-
Oxabicyclo[3,2,1]octan-7-one derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3286881A JPS57145867A (en) | 1981-03-05 | 1981-03-05 | Novel 6-oxabicyclo(3,2,1)octane-7-one derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3286881A JPS57145867A (en) | 1981-03-05 | 1981-03-05 | Novel 6-oxabicyclo(3,2,1)octane-7-one derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57145867A JPS57145867A (en) | 1982-09-09 |
| JPS6412275B2 true JPS6412275B2 (en) | 1989-02-28 |
Family
ID=12370831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3286881A Granted JPS57145867A (en) | 1981-03-05 | 1981-03-05 | Novel 6-oxabicyclo(3,2,1)octane-7-one derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57145867A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4869896A (en) * | 1984-05-30 | 1989-09-26 | Angus Chemical Company | Potentiated insect repellent composition and method |
-
1981
- 1981-03-05 JP JP3286881A patent/JPS57145867A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57145867A (en) | 1982-09-09 |
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