Abstract

ORGANIC PREPARATIONS AND PROCEDURES Ih'T., 27 (2), 185-212 (1995) SYNTHESIS OF AMINOCYCLOBUTANE MONO- AND DICARBOXYLIC ACIDS AND DERIVATIVES THEREOF FROM (PHE"YL)BICYCLOBUTANES Yehiel Gaoni Department of Organic Chemistry The Weimnn Institute of Science, Rehovot 76100, ISRAEL The discovery of the naturally occumng cyclobutane amino acids cis- l-aminocyclobu- tane- 1,3-dicarboxylic acid (cis-2fmethanoglutamic acid, l), 2,4-methanoproline (2),l and cis-I- amino-3-(hydroxymethyl)cyclobutane- 1 -carboxylic acid (3)2 has raised a considerable interest in the synthesis of these acids and of the non natural trans isomers, trans-2,4-methanoglutamic acid (4) and trans- 1-amino-3-(hydroxymethyl)cyclobutane-l-carboxylic acid (5).3-8 Acid 4 was later 1 2 3 HOCH2 4 5 found to be a potent neurotransmitter, with selectivity for one subtype of glutamate The synthetic efforts were then extended to a whole range of cyclobutane amino acids of potential biological interest, particularly as antagonists to neurotransmission8.'O or as substitutes for essential natural amino acids in active peptides." The synthesis of cyclobutane amino acids herein described is based on our general scheme for the preparation of substituted cyclobutanes from 1-(arylsulfonyl)bicyclo[ 1. l.O]butanes. I2J3 The use of this scheme in the preparation of a number of neuroactive amino acids has been described in detail recently.I0 The present article outlines some further applications of this