WO2013167088A3 - L-环状烷基氨基酸的合成方法及具有其的药物组合物 - Google Patents

L-环状烷基氨基酸的合成方法及具有其的药物组合物 Download PDF

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Publication number
WO2013167088A3
WO2013167088A3 PCT/CN2013/080358 CN2013080358W WO2013167088A3 WO 2013167088 A3 WO2013167088 A3 WO 2013167088A3 CN 2013080358 W CN2013080358 W CN 2013080358W WO 2013167088 A3 WO2013167088 A3 WO 2013167088A3
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WIPO (PCT)
Prior art keywords
cyclic alkyl
amino acid
acid
synthesis method
structural formula
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PCT/CN2013/080358
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English (en)
French (fr)
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WO2013167088A2 (zh
Inventor
洪浩
郑长胜
郭莉娜
Original Assignee
凯莱英医药集团（天津）股份有限公司
凯莱英生命科学技术(天津)有限公司
天津凯莱英制药有限公司
凯莱英医药化学（阜新）技术有限公司
吉林凯莱英医药化学有限公司
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Application filed by 凯莱英医药集团（天津）股份有限公司, 凯莱英生命科学技术(天津)有限公司, 天津凯莱英制药有限公司, 凯莱英医药化学（阜新）技术有限公司, 吉林凯莱英医药化学有限公司 filed Critical 凯莱英医药集团（天津）股份有限公司
Priority to PCT/CN2013/080358 priority Critical patent/WO2013167088A2/zh
Priority to US14/783,653 priority patent/US20160319312A1/en
Publication of WO2013167088A2 publication Critical patent/WO2013167088A2/zh
Publication of WO2013167088A3 publication Critical patent/WO2013167088A3/zh

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/04—Alpha- or beta- amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/005—Amino acids other than alpha- or beta amino acids, e.g. gamma amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y104/00—Oxidoreductases acting on the CH-NH2 group of donors (1.4)
    • C12Y104/01—Oxidoreductases acting on the CH-NH2 group of donors (1.4) with NAD+ or NADP+ as acceptor (1.4.1)
    • C12Y104/01009—Leucine dehydrogenase (1.4.1.9)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

本发明提供了一种 L-环状烷基氨基酸的合成方法及具有其的药物组合物。该合成方法包括：步骤 A，制备具有结构式（Ⅰ）或结构式（Ⅱ）的环状烷基酮酸或环状烷基酮酸盐；步骤 B，将环状烷基酮酸或环状烷基酮酸盐与甲酸铵、亮氨酸脱氢酶、甲酸脱氢酶以及辅酶 NAD + 混合，进行还原氨基化反应，生成 L-环状烷基氨基酸，其中，结构式（Ⅰ），n ≥1，m ≥0，M 为 H或一价阳离子；结构式（Ⅱ），n 2 ≥0，m 2 ≥0，M 2 为 H或一价阳离子；亮氨酸脱氢酶的氨基酸序列为 SEQ ID No. 1。利用特定亮氨酸脱氢酶与甲酸脱氢酶、辅酶 NAD + 使环状烷基酮酸发生还原氨基化反应生成 L-环状烷基氨基酸，原料转化率高，手性选择性高。
PCT/CN2013/080358 2013-07-29 2013-07-29 L-环状烷基氨基酸的合成方法及具有其的药物组合物 WO2013167088A2 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/CN2013/080358 WO2013167088A2 (zh) 2013-07-29 2013-07-29 L-环状烷基氨基酸的合成方法及具有其的药物组合物
US14/783,653 US20160319312A1 (en) 2013-07-29 2013-07-29 Synthesis method for l-cyclic alkyl amino acid and pharmaceutical composition having thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2013/080358 WO2013167088A2 (zh) 2013-07-29 2013-07-29 L-环状烷基氨基酸的合成方法及具有其的药物组合物

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WO2013167088A2 WO2013167088A2 (zh) 2013-11-14
WO2013167088A3 true WO2013167088A3 (zh) 2014-07-24

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US (1) US20160319312A1 (zh)
WO (1) WO2013167088A2 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108048317B (zh) * 2017-12-12 2023-08-15 凯莱英医药集团（天津）股份有限公司 一种非天然氨基酸的连续合成系统及连续合成方法
CN112143718B (zh) * 2020-04-30 2023-04-18 重庆医科大学 一种双功能酶生物催化剂及其制备方法和应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101818178A (zh) * 2010-04-15 2010-09-01 尚科生物医药（上海）有限公司 一种酶法制备l-2-氨基丁酸的方法
CN102250976A (zh) * 2011-05-06 2011-11-23 凯莱英医药化学（天津）有限公司 一种手性叔亮氨酸的合成方法及其最终产物
CN102352387A (zh) * 2011-09-19 2012-02-15 尚科生物医药（上海）有限公司 固定化全细胞催化剂合成非天然氨基酸的方法
CN102605014A (zh) * 2012-03-14 2012-07-25 苏州汉酶生物技术有限公司 一种l-2-氨基丁酸的生物制备方法
CN102676599A (zh) * 2012-05-03 2012-09-19 尚科生物医药（上海）有限公司 一种制备(s)-2-氨基环丙基乙酸的方法
CN102807487A (zh) * 2012-09-03 2012-12-05 方正 一种沙格列汀中间体的合成方法
CN102888431A (zh) * 2011-07-19 2013-01-23 陈依军 一种制备l-叔亮氨酸的方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
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CN101818178A (zh) * 2010-04-15 2010-09-01 尚科生物医药（上海）有限公司 一种酶法制备l-2-氨基丁酸的方法
CN102250976A (zh) * 2011-05-06 2011-11-23 凯莱英医药化学（天津）有限公司 一种手性叔亮氨酸的合成方法及其最终产物
CN102888431A (zh) * 2011-07-19 2013-01-23 陈依军 一种制备l-叔亮氨酸的方法
CN102352387A (zh) * 2011-09-19 2012-02-15 尚科生物医药（上海）有限公司 固定化全细胞催化剂合成非天然氨基酸的方法
CN102605014A (zh) * 2012-03-14 2012-07-25 苏州汉酶生物技术有限公司 一种l-2-氨基丁酸的生物制备方法
CN102676599A (zh) * 2012-05-03 2012-09-19 尚科生物医药（上海）有限公司 一种制备(s)-2-氨基环丙基乙酸的方法
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US20160319312A1 (en) 2016-11-03

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