利用脂肪酶Novozym 435催化转酯反应对映选择性合成®-α-硫辛酸的手性前体

Synthesis of a Chiral Precursor for (R) α Lipoic Acid via Novozym 435 Mediated Enantioselective Transesterification

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100 g/mol ECHO，可以耐受的底物浓度为1 mol/L。在产品的克级制备反应中，6 h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471 g/(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。

Abstract: Abstract: 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) O 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/mol 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.