JPH02229152A - Production of cyclic amino acid - Google Patents
Production of cyclic amino acidInfo
- Publication number
- JPH02229152A JPH02229152A JP1050782A JP5078289A JPH02229152A JP H02229152 A JPH02229152 A JP H02229152A JP 1050782 A JP1050782 A JP 1050782A JP 5078289 A JP5078289 A JP 5078289A JP H02229152 A JPH02229152 A JP H02229152A
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- formula
- alkyl
- aryl
- cycloalkyl
- 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.)
- Granted
Links
- -1 cyclic amino acid Chemical class 0.000 title claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000001413 amino acids Chemical class 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 229910052751 metal Inorganic materials 0.000 claims abstract description 7
- 239000002184 metal Substances 0.000 claims abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 5
- 229910052762 osmium Inorganic materials 0.000 claims abstract description 5
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 5
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 5
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 235000010215 titanium dioxide Nutrition 0.000 claims description 7
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 4
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 4
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052707 ruthenium Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 229910044991 metal oxide Inorganic materials 0.000 claims 1
- 150000004706 metal oxides Chemical class 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 abstract description 7
- 150000003862 amino acid derivatives Chemical group 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 2
- 230000001678 irradiating effect Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 2
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- KPNBUPJZFJCCIQ-LURJTMIESA-N methyl L-lysinate Chemical compound COC(=O)[C@@H](N)CCCCN KPNBUPJZFJCCIQ-LURJTMIESA-N 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
- Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】 〔産業−にの利用分野〕 本発明は環状アミノ酸の新規製造方法に関する。[Detailed description of the invention] [Industrial field of use] The present invention relates to a novel method for producing cyclic amino acids.
医薬品等に多用されるアミノ酸類縁化合物、とくにプロ
リンやピペコリン酸などの環状アミノ酸類の製造に利用
される。It is used in the production of amino acid analogs, especially cyclic amino acids such as proline and pipecolic acid, which are often used in pharmaceuticals.
環状アミノ酸類、とくに光学活性化合物の合成法として
は、天然のアミノ酸類を利用してアミノ酸炭素の立体配
置を保持したまま反応させる方法が知られている。（例
えば、Ｌ−リジンからＬピペコリン酸の合成、Ｔｏｓｈ
ｉｙｕｋｉ ら、ブレチン・オブ・ケミカル・ソサエテ
ィ・オブ・ジャパン（Ｂｕｌｌ、Ｃｈｅｍ、Ｓｏｃ、Ｊ
ｐｎ、） 、４８．１３４１−１３４２頁（１９７５）
等）。しかしながら、この反応工程は複雑な数多くの段
階から成り、全工程を通じた収率は高々３０％以下であ
る。As a method for synthesizing cyclic amino acids, particularly optically active compounds, a method is known in which natural amino acids are used and reacted while maintaining the steric configuration of amino acid carbons. (For example, synthesis of L-pipecolic acid from L-lysine, Tosh
iyuki et al., Bulletin of Chemical Society of Japan (Bull, Chem, Soc, J.
pn, ), pp. 48.1341-1342 (1975)
etc). However, this reaction process consists of many complicated steps, and the yield throughout the entire process is at most 30% or less.
本発明は、側鎖にアミノ基を有するアミノ酸誘導体を原
料とし、例えば常温常圧という緩やかな条件下で、簡便
な反応工程により収率良く環状アミノ酸を製造する方法
を開発することを目的とする。The purpose of the present invention is to develop a method for producing a cyclic amino acid in high yield through a simple reaction process using an amino acid derivative having an amino group in the side chain as a raw material under mild conditions such as room temperature and normal pressure. .
本発明者らは側鎖にアミノ基を有するアミノ酸誘導体を
、例えば水溶液の形で好ましくは酸化チタン（ＩＶ）又
はこれにルテニウム、ロジウム、パラジウム、オスミウ
ム、イリジウム、白金等の金属又はその酸化物を担持さ
せた触媒の共存下に、紫外線を作用せしめることにより
目的とする環状アミノ酸を容易に、収率良く製造できる
ことを見出し、この発見に基づき本発明を完成するに到
った。The present inventors prepared an amino acid derivative having an amino group in the side chain, preferably titanium (IV) oxide, or a metal such as ruthenium, rhodium, palladium, osmium, iridium, or platinum, or an oxide thereof, in the form of an aqueous solution. It was discovered that the desired cyclic amino acid could be easily produced in good yield by applying ultraviolet rays in the presence of a supported catalyst, and based on this discovery, the present invention was completed.
本発明の原料物質である側鎖にアミノ基を有する前記ア
ミノ酸誘導体は、−ｉ式
％式％
（式中、Ｒ１は、アミン基を含有し、炭素数２〜１６の
アルキル基、炭素数５〜１６のシクロアルキル基炭素数
６〜１４のアリール基、又は炭素数７〜１６アラルキル
基の、Ｒ２及びＲ３は、相互に異っていてもよく、それ
ぞれ水素原子、炭素数２〜１６のアルキル基、炭素数５
〜１６のシクロアルキル基炭素数６〜１４のアリール基
を、又は炭素数７〜１６のアラルキル基を表わし、ＲＲ
２及びＲ３のいずれか二つは相互に結合して環を形成し
ていてもよい。）で表示されるアミノ酸である。具体例
としでは、例えば、Ｌ−１Ｄ−１又はＤＬ−リジン、オ
ルニチン等などのアミノ酸；これらのアミノ酸のアルキ
ル、アリール、あるいはアラルキルエステル（例えば、
リジンメチルエステル）；これらのアミノ酸の１位にお
けるアルキル、アリーム、又はアラルキル置換体（例え
ば、１−フェニルリジン）などが挙げられる。The amino acid derivative having an amino group in the side chain, which is a raw material of the present invention, is a -i formula % formula % (wherein R1 is an alkyl group containing an amine group and having 2 to 16 carbon atoms, a carbon number 5 ~16 cycloalkyl group, C6-14 aryl group, or C7-16 aralkyl group, R2 and R3 may be different from each other, and each represents a hydrogen atom and an alkyl group having 2-16 carbon atoms. group, carbon number 5
~16 cycloalkyl group represents an aryl group having 6 to 14 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms, RR
Any two of 2 and R3 may be bonded to each other to form a ring. ) is an amino acid represented by Specific examples include amino acids such as L-1D-1 or DL-lysine, ornithine; alkyl, aryl, or aralkyl esters of these amino acids (e.g.
lysine methyl ester); alkyl, allem, or aralkyl substituted products at the 1-position of these amino acids (eg, 1-phenylysine); and the like.
反応系は前記アミノ酸の例えば水溶液と酸化チタン（Ｔ
Ｖ）又はこれにルテニウム、ロジウム、パラジウム、オ
スミウム、イリジウム、白金等の金属又はその酸化物の
単独又は混合物を担持させた触媒の混合物である。アミ
ノ酸類の濃度は分子間反応を防ぐために５％（重量％、
以下同様）以下、特に０．５−１％とするのが好ましい
。触媒に担持させる金属又はその酸化物の担持量は０．
５−５％程度が適当である。The reaction system includes, for example, an aqueous solution of the amino acid and titanium oxide (T
V) or a mixture of catalysts in which metals such as ruthenium, rhodium, palladium, osmium, iridium, platinum, or oxides thereof, singly or in mixtures, are supported thereon. The concentration of amino acids was 5% (wt%) to prevent intermolecular reactions.
The same applies hereinafter) Below, it is particularly preferable to set it as 0.5-1%. The amount of metal or its oxide supported on the catalyst is 0.
Approximately 5-5% is appropriate.
前記アミノ酸の水溶液と例えば酸化チタン（ＩＶ）又は
これにルテニウム、ロジウム、パラジウム、オスミウム
、イリジウム、白金等の金属又はその酸化物の単独又は
混合物を担持させた触媒の混合物を反応容器に入れ、外
部或いは内部から光を照射するとよい。反応は１０〜３
０℃で常圧にて充分進行する。反応雰囲気はアルゴンガ
ス、窒素ガス等の不活性ガス雰囲気とするのが好ましい
。A mixture of the aqueous solution of the amino acid and a catalyst prepared by supporting titanium (IV) oxide or a metal such as ruthenium, rhodium, palladium, osmium, iridium, platinum, or a mixture thereof, alone or in a mixture, is placed in a reaction vessel, and an external Alternatively, light may be irradiated from inside. The reaction is 10-3
The reaction progresses satisfactorily at 0°C and normal pressure. The reaction atmosphere is preferably an inert gas atmosphere such as argon gas or nitrogen gas.
反応容器としては反応混合物中の成分と反応しない材質
のものという条件を満たすものであれば特に限定されな
いが、反応容器外から光を照射する場合には光の透過性
が高いものが好ましい。The reaction vessel is not particularly limited as long as it is made of a material that does not react with the components in the reaction mixture, but when irradiating light from outside the reaction vessel, a vessel with high light transmittance is preferred.
本発明で得られる環状アミノ酸は、例えば−儀式
％式％
で示される化合物である。式中、Ｒ２及びＲ３は前記同
様の意義を有する。Ｒ４は、前記Ｒ′の意義において脱
アミノ基した置換基を意味する。The cyclic amino acid obtained in the present invention is, for example, a compound represented by the formula %. In the formula, R2 and R3 have the same meanings as above. R4 means a deaminated substituent in the meaning of R' above.
光吸収により酸化チタン（ＩＶ ）中に生成した正孔に
よる原料物質の側鎖のアミノ基の酸化と引き続く加水分
解によりアルデヒド基が生し、これと同一分子内のアミ
ノ基との脱水縮合の結果生成した環状イミンが、正孔と
同時に発生した電子により還元されて目的物環状アミノ
酸が生成したものと考えられる。Oxidation of amino groups in the side chains of the raw material by holes generated in titanium (IV) oxide due to light absorption and subsequent hydrolysis generate aldehyde groups, which are dehydrated and condensed with amino groups in the same molecule. It is thought that the generated cyclic imine was reduced by holes and electrons generated at the same time, and the target cyclic amino acid was generated.
次に、本発明の方法を実施例に基づいて説明する。 Next, the method of the present invention will be explained based on examples.
実施例Ｉ
Ｌ ＩＪレシン酸塩２４０■、０．０２規定水酸化す
） ＩＪウム水溶液６０ｍ１、及び酸化白金１０％を添
加した酸化チタン（ＩＶ）６００■を混合し、硬質硝子
試験管に入れた。系内の空気をアルゴンガスで置換して
ゴム栓で密封した後、４００ワツト高圧水銀灯を用いて
５ ｃｍの距離から室温下で４４時間照射した。酸化チ
タン（ＴＶ）を遠心分離により取り除いた後、上澄み液
の水分を大部分留去し、陽イオン交換樹脂筒を通過させ
た。ニンヒドリン試薬により発色する留分を濃縮して、
吸湿性の淡黄色の粉末を得た。５６■、単離収率３３％
。単離生成物を重水に溶解し３−（）ＩＪメチルシリル
）プロピオン酸ナトリウム−２，２，３，３−ｄ４（以
下ｒＴＰｓＪと略す）を基準物質（Ｏｐｐｍ）としてプ
ロトンＮＭＲ測定を行うと、光照射前の試料に認められ
た１、４．３．０．３．４ｐｐｍのりシンに由来するピ
ークが消失し、代わりに１．８．２．２．３．１．３．
４、および３．６ ｐｐＨｌにピペコリン酸に特徴的な
ピークを１ｉＩＩ認した。（２，３，４，６−テトラ０
−アセチル−β−Ｄ−グルコピラノシルイソチオシアネ
ート（以下ｒＧＩＴｃＪと略す）により誘導体化した試
料の逆相系高速液体クロマトグラフ分析によりＬ体７４
％、０体２６％と求められた。Example I L 240 ml of IJ lecinate, 0.02 N hydroxide solution) and 600 ml of titanium (IV) oxide to which 10% platinum oxide was added were mixed and placed in a hard glass test tube. . After replacing the air in the system with argon gas and sealing it with a rubber stopper, it was irradiated for 44 hours at room temperature from a distance of 5 cm using a 400 Watt high pressure mercury lamp. After removing titanium oxide (TV) by centrifugation, most of the water in the supernatant was distilled off, and the supernatant was passed through a cation exchange resin column. Concentrate the fraction that develops color with ninhydrin reagent,
A hygroscopic pale yellow powder was obtained. 56■, isolated yield 33%
. When the isolated product was dissolved in heavy water and proton NMR measurement was performed using sodium 3-()IJmethylsilyl)propionate-2,2,3,3-d4 (hereinafter abbreviated as rTPsJ) as a reference material (Oppm), light was detected. The peaks derived from 1, 4, 3, 0, 3, 4 ppm glue, which were observed in the sample before irradiation, disappeared and were replaced by 1, 8, 2, 2, 3, 1, 3.
4 and 3.6 ppHl, peaks characteristic of pipecolic acid were observed. (2,3,4,6-tetra0
-L-form 74 was determined by reversed-phase high performance liquid chromatography analysis of a sample derivatized with -acetyl-β-D-glucopyranosyl isothiocyanate (hereinafter abbreviated as rGITcJ).
%, 0 body 26%.
実施例２
実施例１におけるＬ−リシン塩酸塩２４０ｎｗに代えて
Ｌ−オルニチン塩酸塩３００ｎｖを用い、同一条件下で
反応させてプロリン８９■を得た。単離収率４３％。単
離生成物の重水溶液のプロトンＮＭＲスペクトルには、
光照射前の試料に認められた１、８．３．０．３．５
ｐｐｍのオルニチンに由来するピークは認められず、代
わりに２．０．２．４．３．４、および４．１ ｐｐｍ
にプロリンに特徴的なピークを確認した。ＧＩＴＣによ
り誘導体化した生成物の逆相系高速液体クロマトグラフ
分析により、Ｌ体６４％、０体３６％と求められた。Example 2 300 nv of L-ornithine hydrochloride was used in place of 240 nw of L-lysine hydrochloride in Example 1, and the reaction was carried out under the same conditions to obtain 89 ■ of proline. Isolated yield 43%. The proton NMR spectrum of a heavy aqueous solution of the isolated product includes:
1, 8.3.0.3.5 observed in the sample before light irradiation
No peaks derived from ornithine at ppm were observed, but instead at 2.0.2.4.3.4, and 4.1 ppm.
A peak characteristic of proline was confirmed. Reversed-phase high performance liquid chromatography analysis of the product derivatized by GITC determined that the L-form was 64% and the 0-form was 36%.
実施例３
Ｌ−リシン塩酸塩２０■、蒸溜水５ｍβ、及び酸化白金
５％を添加した酸化チタン（ＴＶ）５０■の混合物を含
む硬質硝子試験管を４木調製した。Example 3 Four hard glass test tubes containing a mixture of 20 μm of L-lysine hydrochloride, 5 mβ of distilled water, and 50 μm of titanium oxide (TV) to which 5% platinum oxide was added were prepared.
このうち３木のそれぞれに、０．１規定水酸化ナトリウ
ム水溶液を０．０４．０．１、及び０．５ｍ６添加し、
混合物の初期ｐｌ＋を第１表に示す値に調整した。Of these, 0.04, 0.1, and 0.5 m6 of 0.1N aqueous sodium hydroxide solution were added to each of the three trees,
The initial pl+ of the mixture was adjusted to the values shown in Table 1.
残る１木は水酸化ナトリウム水溶液を加えずにそのまま
使用した。試験管内の空気をアルゴンガスで置換してゴ
ム栓で密封した後、４００ワソＩ・高圧水銀灯を用いて
５ ｃｍの距離から室温下で２４時間照射した。遠心分
離により酸化チタン（ＩＶ）を取り除いた上澄みにＧｒ
ＴＣを作用させて誘導体化し、ＨＰＬＣを用いて収率な
らびに不斉収率を測定した結果を第１表に示す。The remaining one tree was used as it was without adding an aqueous sodium hydroxide solution. After replacing the air in the test tube with argon gas and sealing it with a rubber stopper, it was irradiated for 24 hours at room temperature from a distance of 5 cm using a 400 waso I high pressure mercury lamp. Gr is added to the supernatant after removing titanium (IV) oxide by centrifugation.
Table 1 shows the results of derivatization with TC and measurement of yield and asymmetric yield using HPLC.
第１表
第１表から明らかな如く、初期ｐＨを小さくすると、単
位時間あたりのし一リシン転化率は若干低下するものの
不斉収率が向上する。As is clear from Table 1, when the initial pH is decreased, the asymmetric yield improves, although the conversion rate of lysine per unit time slightly decreases.
以上から明らかな如く、本発明の方法によれば、原料物
質の立体配置を保持した環状アミノ酸の優先的合成を常
温常圧下で容易に行うことが出来るので、
本発明は、
環状アミノ酸の製造分野、
或は
医薬品製造分野で極めて有用である。As is clear from the above, according to the method of the present invention, preferential synthesis of a cyclic amino acid that maintains the configuration of the raw material can be easily carried out at room temperature and normal pressure. , or extremely useful in the pharmaceutical manufacturing field.
特 許 出 願 人 鍵 谷 勤 味の素株式会社Special permission Out wish Man Key Tani Tsutomu Ajinomoto Co., Inc.
Claims (1)
とする環状アミノ酸の製造方法。 但し、式中、Ｒ＾１は、一級アミノ基を含有し、アルキ
ル、シクロアルキル、アリール、又はアラルキル基を、
Ｒ＾２及びＲ＾３は、相互に異っていてもよく、それぞ
れ水素原子、又はアルキル、シクロアルキル、アリール
若しくはアラルキル基を、それぞれ表わすが、Ｒ＾１、
Ｒ＾２及びＲ＾３のいずれか二つが相互に結合して環を
形成してもよい。 ２、紫外線を作用せしめる際酸化チタン（IV）又はこれ
に金属若しくは金属酸化物を担持させた触媒が存在する
請求項１記載の方法。 ３、金属がルテニウム、ロジウム、パラジウム、オスミ
ウム、イリジウム、及び白金の少なくとも一種である請
求項２記載の方法。 ４、アミノ酸が水溶液の状態で存する請求項１記載の方
法。 ５、環状アミノ酸が一般式： ▲数式、化学式、表等があります▼ で示されるものである請求項１記載の方法。 但し、式中、Ｒ＾２及びＲ＾３は、相互に異っていても
よく、それぞれ水素原子、又はアルキル、シクロアルキ
ル、アリール若しくはアラルキル基を、Ｒ＾４は、アル
キル、シクロアルキル、アリール又はアラルキル基を、
それぞれ表わすが、Ｒ＾２、Ｒ＾３及びＲ＾４のいずれ
か二つが相互に結合して環を形成してもよい。[Claims] 1. A method for producing a cyclic amino acid, which comprises exposing an amino acid represented by the general formula (numerical formula, chemical formula, table, etc.) to ultraviolet light. However, in the formula, R^1 contains a primary amino group, and represents an alkyl, cycloalkyl, aryl, or aralkyl group,
R^2 and R^3 may be different from each other and each represents a hydrogen atom, or an alkyl, cycloalkyl, aryl or aralkyl group, but R^1,
Any two of R^2 and R^3 may be bonded to each other to form a ring. 2. The method according to claim 1, wherein titanium (IV) oxide or a catalyst in which a metal or metal oxide is supported on titanium (IV) oxide is present when the ultraviolet rays are applied. 3. The method according to claim 2, wherein the metal is at least one of ruthenium, rhodium, palladium, osmium, iridium, and platinum. 4. The method according to claim 1, wherein the amino acid is present in an aqueous solution. 5. The method according to claim 1, wherein the cyclic amino acid has a general formula: ▲A mathematical formula, a chemical formula, a table, etc.▼. However, in the formula, R^2 and R^3 may be different from each other and each represents a hydrogen atom or an alkyl, cycloalkyl, aryl or aralkyl group, and R^4 represents an alkyl, cycloalkyl, aryl group. Or an aralkyl group,
Although each is represented, any two of R^2, R^3 and R^4 may be bonded to each other to form a ring.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1050782A JP2866098B2 (en) | 1989-03-02 | 1989-03-02 | Method for producing cyclic amino acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1050782A JP2866098B2 (en) | 1989-03-02 | 1989-03-02 | Method for producing cyclic amino acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02229152A true JPH02229152A (en) | 1990-09-11 |
| JP2866098B2 JP2866098B2 (en) | 1999-03-08 |
Family
ID=12868398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1050782A Expired - Lifetime JP2866098B2 (en) | 1989-03-02 | 1989-03-02 | Method for producing cyclic amino acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2866098B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6172234B1 (en) | 1998-07-27 | 2001-01-09 | Sumitomo Chemical Company, Limited | Optically active cyclic amino acid ester derivatives and processes for producing the same |
| US6245588B1 (en) * | 1996-04-19 | 2001-06-12 | Rohm Co., Ltd | Semiconductor light-emitting device and method of manufacturing the same |
-
1989
- 1989-03-02 JP JP1050782A patent/JP2866098B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6245588B1 (en) * | 1996-04-19 | 2001-06-12 | Rohm Co., Ltd | Semiconductor light-emitting device and method of manufacturing the same |
| US6172234B1 (en) | 1998-07-27 | 2001-01-09 | Sumitomo Chemical Company, Limited | Optically active cyclic amino acid ester derivatives and processes for producing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2866098B2 (en) | 1999-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0272787B1 (en) | Catalytic production of optically active carboxylic acid | |
| JPS61275241A (en) | Production of deuterated acrylic acid or methacrylic acid | |
| Deseke et al. | Intrinsic reactivities of amino acids towards photoalkylation with benzophenone− a study preliminary to photolabelling of the transmembrane protein glycophorin A | |
| JPH02229152A (en) | Production of cyclic amino acid | |
| CA1042917A (en) | Method for racemization of optically active amines | |
| Russ et al. | The controlled stereospecific reduction of cyclopentenyl cytosine (CPE-C) to carbodine and isocarbodine | |
| Steenhoek et al. | Optimization, mechanism, and kinetics of the hydrogenation of skipped polyynoic acids to all‐cis skipped polyenoic acids | |
| EP2732874B1 (en) | Method for synthesising heterogeneous solid chiral catalysts and their use in stereoselective reactions | |
| CN1023121C (en) | Crystal of hydrochloric salt of etoposide-2-dimethylamino compounds and process for preparing them | |
| JPH01233255A (en) | Cyclopentenone derivative and production thereof | |
| Maihub et al. | Amino Acids as Substrates in the Synthesis of Substituted Organocobalamins | |
| US3401106A (en) | Process for the photochemical alkylation of lactones and lactams | |
| Rilling | [14] Photoaffinity substrate analogs for eukaryotic prenyltransferase | |
| Lomölder et al. | Low‐Temperature Photolysis of Peracetylated Dodecanoyl Peroxides of Tartaric Acid and d‐Gluconic Acid in the Solid State—A Diastereoselective Radical Coupling | |
| JPH0227995A (en) | Production of l-carnitine chloride | |
| JPH0331245A (en) | Production of hydroxy-n-acyl-alpha-amino acid derivative | |
| Matsukawa et al. | Synthesis of D-and L-selenomethionine double-labeled with deuterium and selenium-82 | |
| JPS5951227A (en) | Manufacture of pinane derivative | |
| JP3845723B2 (en) | Alkylamino group introduction method and amino acid synthesis method | |
| JPS6251267B2 (en) | ||
| JP3529876B2 (en) | 3-methyl-3-methoxybutanoic acid. | |
| JPH06135906A (en) | Method for racemizing optically active diamine | |
| JPH0656769A (en) | Method of selective photochemical reaction using tartaric acid derivative | |
| US2862030A (en) | Preparation of vitamin a aldehyde | |
| Chen et al. | A synthesis of N 6, N 6, N 6-trimethyl-L-lysine dioxalate in gram amounts |