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Stereoselective Synthesis of Three Isomers of tert ‐Butyl 5‐Hydroxy‐4‐methyl‐3‐oxohexanoate through Alcohol Dehydrogenase‐Catalyzed Dynamic Kinetic Resolution
Author(s) -
Lüdeke Steffen,
Richter Michael,
Müller Michael
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200800619
Subject(s) - chemistry , kinetic resolution , yield (engineering) , stereoselectivity , alcohol dehydrogenase , alcohol , regioselectivity , catalysis , stereochemistry , enantiomeric excess , enantioselective synthesis , medicinal chemistry , organic chemistry , materials science , metallurgy
Regioselective reduction of the 5‐keto group of tert ‐butyl 4‐methyl‐3,5‐dioxohexanoate ( 1 ) leads to a stereodiad of tert ‐butyl 5‐hydroxy‐4‐methyl‐3‐oxohexanoate ( 2 ). Alcohol dehydrogenases from Lactobacillus brevis (LBADH), Rhodococcus sp. (RS 1‐ADH) and Saccharomyces cerevisiae (YGL157w) reduce 1 under dynamic kinetic resolution conditions, thereby establishing two chiral carbons with a single reduction step. While it had been shown previously that LBADH reduction of 1 stereoselectively leads to syn ‐(4 S ,5 R )‐ 2 , alcohol dehydrogenase‐mediated dynamic kinetic resolution now allows easy access to syn ‐(4 R ,5 S )‐ 2 (RS 1‐ADH; 97.6% ee , syn : anti =92:8, 66% conversion, 37% isolated yield) and anti ‐(4 S ,5 S )‐ 2 (YGL157w; 90% ee , anti:syn =93:7, 64% conversion, 42% isolated yield), as well. Thus three out of four possible stereoisomers were formed selectively upon reduction of 1 .