Synthesis of enantiopure glycidol derivatives via a one-pot two-step enzymatic cascade

Abstract

Styrene monooxygenase (SMO) can catalyze the kinetic resolution of secondary allylic alcohols to provide enantiopure glycidol derivatives. To overcome the low theoretical yield of kinetic resolution, we designed a one-pot two-step enzymatic cascade using prochiral α,β-unsaturated ketones as the substrates. An S-specific ketoreductase ChKRED03 was screened for the efficient bioreduction of the substrates to provide (S)-allylic alcohols, which underwent SMO-catalyzed epoxidation to achieve glycidol derivatives with contiguous stereogenic centers. Excellent enantioselectivity (ee > 99%) and diastereoselectivity (de > 99%) were achieved for the majority of the substrates, and product yields reached up to >99%.

Two-Component FAD-Dependent Monooxygenases: Current Knowledge and Biotechnological Opportunities

“…have been characterized in detail [ 121 , 129 , 130 , 131 , 132 ]. StyAs showed the ability to convert a variety of styrene derivatives as well as aryl alkyl sulfides in a regio- and enantioselective manner [ 43 , 121 , 129 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 ].…”

Efficient bioreductive production of (S)-N-Boc-3-hydroxypiperidine using ketoreductase ChKRED03

“…ChKRED03 is known to be NADPH-dependent [24]. For the substrate NBPO, the activity of ChKRED03 was determined to be 6.27 U/mg in the presence of NADPH, and 0.15 U/mg in the presence of NADH.…”

Asymmetric bio-epoxidation catalyzed with the styrene monooxygenase from Pseudomonas sp. LQ26

“…Particularly, the SMO from Pseudomonas taiwanensis VLB120 (Volmer et al 2014) has been successfully scaled up in the production of enantiopure (S)-styrene oxide (Panke et al 2002). Further investigation Open Access *Correspondence: wuzhl@cib.ac.cn 1 Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences, 9 South Renmin Road, 4th Section, Chengdu 610041, Sichuan, People's Republic of China Full list of author information is available at the end of the article has expanded its substrate spectrum to styrene derivatives and analogs (Lin et al 2011c;Liu et al 2015), as well as aliphatic olefins (Toda et al 2015). Compared with classic chemo-catalysts and hydrolytic kinetic resolution to achieve optically pure styrene oxide, SMO catalyzes the epoxidation of styrene and derivatives with exquisite regio-and enantioselectives under moderate reaction conditions, providing an attracting alternative for the synthesis of chiral epoxides (Bernasconi et al 2000;Lin et al 2010;Schmid et al 2001).…”