SYNTHESIS OF CONFORMATIONALLY RESTRICTED CHIRAL GAMMA-AMINOBUTYRIC-ACID (GABA) ANALOGS

The epimeric (2S, 3S)- and (2R, 3S)-3-amino-2-(carboxymethyl)oxolanes have been synthesised from (S)-N-tritylhomoserine lactone. The lactone was first reduced with diisobutylaluminium hydride to a diastereomeric mixture of the corresponding lactols which underwent Wittig olefination to give methyl (4S)-(E)-6-hydroxy-4-tritylaminohex-2-enoate. Fluoride-ion induced ring-closure gave a mixture of (2S, 3S)- and (2R, 3S)-oxolanes. After chromatographic separation and deprotection these yielded the required products. Application of the initial reduction to the bicyclic cis-N-trityl-4-hydroxyproline lactone failed to provide the corresponding lactol mixture, although this could be obtained indirectly by way of the corresponding methyl ester. While the lactol did indeed undergo olefination to yield (2S, 4S)-4-hydroxy-2-[(E)-2-(methoxycarbonyl)]ethenyl-1-tritylpyrrolidine, this latter could not be cyclised.