Enzyme-catalysed kinetic resolution of 4-endo-hydroxy-2-oxabicyclo[3.3.0]oct-7-en-3-one and employment of the pure enantiomers for the synthesis of anti-viral and hypocholestemic agents.
The endo-hydroxylactone (+/-)-(1) was resolved by enantioselective acetylation using Candida cylindracea lipase or preferentially Pseudomonas fluorescens lipase (pfl). Alternatively the corresponding butyrate (+/-)-(3) was hydrolysed with pfl to give the ester (+)-(1S,4R,5S)-(3) and the alcohol (-)-(1R,4S,5R)-(1). The latter compound was converted into carbovir (-)-(1R,4S)-(12) while the ester (+)-(3) was transformed into the delta-lactone (+)-(3R,5S)-(18). The exo-hydroxylactone (+/-)-(2) was resolved less efficiently by a trans-esterification process employing pfl and vinyl acetate.
MacKeith
R A
RA
Department of Chemistry, Exeter University, Devon, U.K.
McCague
R
R
Olivo
H F
HF
Roberts
S M
SM
Taylor
S J
SJ
Xiong
H
H
D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000302:isolation & purification; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002175:Candida / Q000201:enzymology; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D007700:Kinetics; D008049:Lipase; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009904:Optical Rotation; D011551:Pseudomonas fluorescens / Q000201:enzymology; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
C091059:4-hydroxy-2-oxabicyclo(3.3.0)oct-7-en-3-one; D000924:Anticholesteremic Agents; D000998:Antiviral Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015224:Dideoxynucleosides; D007202:Indicators and Reagents; C057503:carbovir; D008049:Lipase