Sandeep Raghunath Ghorpade

Enzymatic kinetic resolution studies of racemic 4-hydroxycyclopent-2-en-1-one using Lipozyme IM®

Abstract Enzymatic kinetic resolution studies of (±)-4-hydroxycyclopent-2-en-1-one 2 were taken up in organic solvents by transesterification with vinyl acetate and alcoholysis of its acetate 3 as an alternative to the desymmetrization of meso-cyclopentenediol to provide faster and economic access to enantiomerically pure 4-(R)-tert-butyldimethylsilyloxycyclopent-2-en-1-one 1. Parameters were screened using Lipozyme IM® as catalyst. Although enantioselectivity observed was moderate (E=24, by alcoholysis of 3 with 2-butanol), trends in the effect of solvent, water content and alcohol structure showed useful directions for screening of other enzymes for optimization of the method to useful levels of efficiency.

Desymmetrization of meso-cyclopenten-cis-1,4-diol to 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate by irreversible transesterification using Chirazyme®

Abstract The parameter optimization study for the desymmetrization of meso-cyclopenten-1,4-diol 1 through irreversible transesterification using an immobilized lipase from Mucor meihei, i.e., Lipozyme®/Chirazyme® is presented. The enzyme was studied for the transesterification of 1 in various organic solvents by varying reaction parameters such as the nature of acyl donor, temperature, enzyme quantity etc., to afford optically active 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate 2 of >98% enantiomeric excess in >60% yield.

A practical and scalable process for 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate by desymmetrization of meso-cyclopent-2-en-1,4-diacetate catalyzed by Trichosporon beigelii (NCIM 3326), a cheap biocatalyst

Abstract Various yeast and fungal cultures from NCIM, NCL, Pune, India were screened for the hydrolysis of meso -cyclopent-2-en-1,4-diacetate 2 to 4-( R )-hydroxycyclopen-2-en-1-( S )-acetate 1 to provide a cheaper and more effective alternative to PLE which is currently being used for the conversion. Yeast cultures of Trichosporon species were identified as having a pro- R preference in the hydrolysis of 2 ; but the enantioselectivity was poor. Hence detailed medium-engineering investigations were made for the hydrolysis of 2 to 1 using a culture of Trichosporon beigelii (NCIM 3326) as catalyst. Addition of 10% v/v ethanol was found to enhance the enantioselectivity of the enzyme, affording 1 of 85% optical purity (op) in 83% yield. Further exploration of inherent consecutive kinetic resolutions to the desymmetrization afforded 1 of >98% op in 74% chemical yield.