Synthesis of (1R,3R,5S)-1-Amino-3-(hydroxymethyl)bicyclo[3.1.0]hexane as a Precursor for the Synthesis of Carbocyclic Nucleosides

Abstract

The stereocontrolled synthesis has been achieved of a 1,5-methano-1- amino-5-(hydroxymethyl)-cyclopentane, a potential component for carbo- cyclic nucleosides. Stereocontrol was manifest by converting (R)-2-(( benzyloxy)ethyl)oxirane specifically to (2S,3S)-2-amino-2,3-methanoadi- pate through a series of lactones. This aminocyclopropanecarboxylate was then cyclized to the corresponding cyclopentanone ester. Reduction of the ketone, elimination, and hydrogenation of the double bond led primarily to the cyclopentane with the amino and ester groups trans (9/1). Enolization followed by an ammonium chloride quench then inver- ted this to a mixture in which the cis isomer was dominant (4/1). Simple functional group manipulation then gave the target (1R,3R,5S)-1-amino- 3-(hydroxymethyl)bicyclo[3.1.0]hexane