通过脂肪酶和ω-转氨酶合成对映体纯的反式-(1R,2R)-和顺式-(1S,2R)-1-氨基-2-茚醇。

Synthesis of enantiomerically pure trans-(1R,2R)- and cis-(1S,2R)-1-amino-2-indanol by lipase and omega-transaminase.

作者信息

Yun Hyungdon, Kim Juhan, Kinnera Koteshwar, Kim Byung-Gee

机构信息

Laboratory of Biotechnology and Biomaterials, Institute of Molecular Biology and Genetics, School of Chemical and Biological Engineering, Seoul National University, Seoul, 151-742, Korea.

出版信息

Biotechnol Bioeng. 2006 Feb 5;93(2):391-5. doi: 10.1002/bit.20721.

DOI:10.1002/bit.20721

PMID:16302257

Abstract

Syntheses of trans-(1R,2R) and cis-(1S,2R)-1-amino-2-indanol (AI) were accomplished by a series of enantioselective enzymatic reactions using lipase and transaminase (TA). Lipase catalysed enantioselective hydrolysis of 2-acetoxyindanone was employed to prepare (R)-2-hydroxy indanone (HI). trans-AI (5 mM) (de > 98%) was produced from 20 mM (R)-2- HI using omega-TA and 50 mM (S)-1-aminoindan as an amino donor in water-saturated ethyl acetate. For the production of cis-AI, the diastereomeric (2R)-AI was synthesized from (R)-2-HI using reductive amination, and the kinetic resolution was performed with omega-TA. The enantioselectivity of omega-TA for (2R)-AI was increased to 22.1 in the presence of 5% gamma-cyclodextrin. cis-AI (15.4 mM) (96% de) was obtained from 40 mM (2R)-AI using 30 mM pyruvate and omega-TA (25 mg) in 10 mL of 100 mM phosphate buffer (pH 7.0).

摘要

通过使用脂肪酶和转氨酶（TA）进行一系列对映选择性酶促反应，完成了反式 -（1R，2R）和顺式 -（1S，2R）-1 - 氨基 - 2 - 茚满醇（AI）的合成。利用脂肪酶催化2 - 乙酰氧基茚满酮的对映选择性水解来制备（R）-2 - 羟基茚满酮（HI）。在水饱和乙酸乙酯中，使用ω - TA和50 mM（S）-1 - 氨基茚满作为氨基供体，从20 mM（R）-2 - HI制备反式 - AI（5 mM）（对映体过量> 98%）。对于顺式 - AI的制备，通过还原胺化从（R）-2 - HI合成非对映异构体（2R）-AI，并使用ω - TA进行动力学拆分。在5%γ - 环糊精存在下，ω - TA对（2R）-AI的对映选择性提高到22.1。在10 mL 100 mM磷酸盐缓冲液（pH 7.0）中，使用30 mM丙酮酸和ω - TA（25 mg），从40 mM（2R）-AI获得顺式 - AI（15.4 mM）（对映体过量96%）。