Kinetic Enzymatic Resolution of Alkyl tetrahydro-4-methylene-2-alkyl-5-oxo-3-furancarboxylates

Tetrahydro-4-methylene-2-alkyl-5-oxo-3-furancarboxylic acids belong to the class of paraconic acids which are characterized by the gamma-lactone moiety, an alkyl chain at C-2, a carboxylic group at C-3, and a methyl or a methylene group at C-4.1) Paraconic acids having a methylene group at C-4 are in general biologically active natural compounds. A few of them are listed in Figure 1.The methyl and ethyl esters of methylenolactocin 2 and C75 3 were synthesized in racemic form following the procedure reported by Carlson and Oyler 2) and they were resolved by enzymatic hydrolysis. (–)-Methylenolactocin was obtained with 80% e.e. using alfa-chymotrypsin (alfa-CT) while (+)-methylenolactocin and (+)-C75 were obtained with 76% e.e. and 96% e.e. 3) respectively, using Acylase I. References: 1) Bandichhor, R.; Nosse, B.; Reiser, O. Top. Curr. Chem. 2005, 243, 43–72. 2) Carlson, R.; Oyler, A. J. Org. Chem. 1976, 41, 4065–4069. 3) Chakrabarty, K.; Forzato C.; Nitti, P.; Pitacco G.; Valentin, E. Letters in Organic Chemistry 2010, 7, 245-248.