Lipase-catalyzed kinetic resolution of cyclic trans-1,2-diols bearing a diester moiety: synthetic application to chiral seven-membered-ring alpha,alpha-disubstituted alpha-amino acid.
Chiral cycloalkane-trans-1,2-diols (+/-)-3 and (+/-)-8 having a diester moiety have been prepared from dimethyl dialkenylmalonate using olefin metathesis by Grubbs catalyst, followed by epoxidation and acidic hydrolysis. Kinetic resolution of racemic cyclopentane-trans-1,2-diol (+/-)-3 by lipase-catalyzed transesterification afforded an optically active monoacetate (-)-5 of 95% ee in 46% yield and the recovered diol (-)-3 of 92% ee in 51% yield, and that of cycloheptane-trans-1,2-diol (+/-)-8 gave a monoacetate (+)-10 of 95% ee in 51% yield and the diol (-)-8 of >99% ee in 43% yield, respectively. The enantiomer selectivity of racemic cyclic trans-1,2-diols bearing a diester moiety by lipases (Amano PS and Amano AK) was opposite to that of the reported simple racemic cycloalkane-trans-1,2-diols. To explain the lipase-catalyzed enantiomer selectivity, computer modeling of lipase-substrate complexes was performed. Furthermore, the optically active diester (-)-8 could be efficiently converted into an optically active seven-membered-ring alpha,alpha-disubstituted amino acid (4R,5R)-(-)-15.
Tanaka
Masakazu
M
Division of Organic Chemistry, National Institute of Health Sciences, Tokyo 158-8501, Japan. mtanaka@phar.kyushu-u.ac.jp
Demizu
Yosuke
Y
Nagano
Masanobu
M
Hama
Mariko
M
Yoshida
Yukio
Y
Kurihara
Masaaki
M
Suemune
Hiroshi
H
D000438:Alcohols / Q000737:chemistry*; D000598:Amino Acids, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D003508:Cycloheptanes / Q000138:chemical synthesis* / Q000737:chemistry; D003517:Cyclopentanes / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D008958:Models, Molecular; D013237:Stereoisomerism
D000438:Alcohols; D000598:Amino Acids, Cyclic; D003508:Cycloheptanes; D003517:Cyclopentanes; D004952:Esters; D008049:Lipase