摘要
利用商品脂肪酶Novozym 435介导的对映选择性转酯反应催化拆分(R,S)-6-羟基-8-氯辛酸乙酯(ECHO),以合成(R)-α-硫辛酸的手性前体。对酶促拆分反应的条件进行了优化,确定了该酶的最适反应条件:以乙酸乙烯酯为酰基供体,最适反应温度为50°C,以异丙醚为反应介质,酶最适上载量为100g/mol ECHO,可以耐受的底物浓度为1mol/L。在产品的克级制备反应中,6h底物转化率为47%,产物(R)-6-乙酰氧基-8-氯辛酸乙酯的对映体过量值(eep)为90%,时空产率高达471g/(L·d),产品总收率为36.3%。该酶法催化的转酯化反应为(R)-α-硫辛酸的合成提供了一条新的途径。
An efficient process by lipase-catalyzed transesterification to synthesize optically pure ethyl 8-chloro-6-hydroxy octanoate （ECHO）, an important chiral precursor for the synthesis of （R）-α-lipoic acid, was developed. The conditions of enzymatic resolution were optimized. The production of （R）-α- acetylated ECHO was achieved in 90% eep, 47% conversion within 6 h, 36.3% isolated yield and 471 g/ （L · d） space-time yield on a gram-scale synthesis using vinyl acetate as acyl donor, diisopropyl ether as solvent, with 100 g/tool ECHO catalyst loading and 1 mol/L substrate loading at 50 ℃. This process provides a new way for the preparation of （R）-α-lipoic acid precursor.
出处
《华东理工大学学报（自然科学版）》
CAS
CSCD
北大核心
2014年第1期53-57,119,共6页
Journal of East China University of Science and Technology
基金
国家自然科学基金(31200050
21276082)
国家"863"计划(2011AA02A210
2011CB710800)
