A new chemoenzymatic approach to the synthesis of Latanoprost and Bimatoprost

被引:17
作者
Contente, Martina Letizia [1 ]
Zambelli, Paolo [1 ]
Galafassi, Silvia [1 ]
Tamborini, Lucia [2 ]
Pinto, Andrea [2 ]
Conti, Paola [2 ]
Molinari, Francesco [1 ]
Romano, Diego [1 ]
机构
[1] Univ Milan, Dept Food Environm & Nutr Sci DeFENS, I-20133 Milan, Italy
[2] Univ Milan, Dept Pharmaceut Sci DISFARM, I-20133 Milan, Italy
关键词
Pichia anomala; Latanoprost; Bimatoprost; Biotransformation; Multi-enzyme processes; ANTIGLAUCOMA AGENTS; PICHIA-GLUCOZYMA; PROSTAGLANDIN; REDUCTION; ANALOGS; YEAST; STRATEGIES;
D O I
10.1016/j.molcatb.2014.05.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bimatoprost (1) and Latanoprost (2) are prostaglandin analogues widely used for glaucoma treatment. We have developed a new chemoenzymatic synthesis for 1 and 2, which utilizes a highly stereoselective sequence of biotransformations catalyzed by enzymes belonging to a single microorganism (the yeast Pichia anomala). The original synthesis, starting from (-)-Corey lactone benzoate (3aR,4R,5R,6aS)-3, was modified by replacing three synthetic steps (C=C reduction, stereoselective C=0 reduction and hydrolysis/deprotection of the benzoate ester) with a one-pot, three-enzymes reaction. The overall biotransformation gave good yields and it was highly stereoselective; noteworthy, by engineering the reaction medium, C=C reduction could be modulated so that unsaturated (3aR,4R,5R,6aS,3'S)-6 or saturated intermediate (3aR,4R,5R,6aS,3'R)-7 could be preferentially obtained. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:7 / 12
页数:6
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