ASYMMETRIC SYNTHESES OF ALL 4 STEREOISOMERS OF 2,3-METHANOMETHIONINE

Asymmetric syntheses of all four stereoisomers of 2,3-methanomethionine ((Z)- and (E)-cyclo-Met) are described. The source of chirality in these reactions is the trifluoromethylsulfonate ester 1b which reacts with di-tert-butyl malonate via direct displacement of trifluoromethylsulfonate followed by lactonization to give 1-(tert-butoxycarbonyl)-2-oxo-3-oxabicyclo[3.1.0]hexane (2). Conversion of compound 2 into (Z)-cyclo-Met can be achieved via ring opening of the lactone, Hoffmann rearrangement, mesylation, and displacement with thiomethoxide. A route to (E)-cyclo-Met was developed using a lipase to effect a critical ester hydrolysis.