Utilizing hydrolases of opposite enantiopreference for the preparation of both enantiomers of (1R,7aR)-(-)- and (1S,7aS)-(+)-3,6,7,7a-tetrahydro-1-hydroxy-7a-methyl-1H-inden-5(2H)-one.
Four racemic esters of (1R*,7aR*)-3,6,7,7a-tetrahydro-1-hydroxy-7a-methyl-1H-inden-5(2H)-one were prepared and subjected to hydrolysis with two types of hydrolases, including alcalase and three lipases. Alcalase and lipase showed opposite enantiopreference on these esters. Based on this result, we developed a gram-scale procedure using butanoate as the substrate, which was treated consecutively with alcalase and lipase from Candida rugosa (CRL), to give both enantiomers of the title compound in high yields and high enantiomeric excess.
Lo
Lee-Chiang
LC
Department of Chemistry, National Taiwan University, Taipei, Taiwan. lclo@ccms.ntu.edu.tw
Chou
Tzyy-Chao
TC
Shie
Jung-Jing
JJ
D002175:Candida / Q000201:enzymology; D007192:Indenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification*; D008049:Lipase / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D013381:Subtilisins / Q000378:metabolism
D007192:Indenes; D008049:Lipase; D013381:Subtilisins