THE ENANTIOSELECTIVE SYNTHESIS OF BETA-AMINO ACIDS, THEIR ALPHA-HYDROXY DERIVATIVES, AND THE N-TERMINAL COMPONENTS OF BESTATIN AND MICROGININ

L-Aspartic acid by tosylation, anhydride formation, and reduction with NaBH4 was converted into (3S)-3-(tosylamino)butan-4-olide (8; Scheme 1). Treatment of 8 with ethanolic trimethylsilyl iodide gave the N-pro tected deoxy-iodo-P-homoserine ethyl ester 9. The latter, on successiv e nucleophilic displacement with lithium dialkylcuprates (-->10a-e), a lkaline hydrolysis (-->11a-e), and reductive removal of the tosyl grou p, produced the corresponding 4-substituted (SR)-9-aminobutanoic acids 12a-e (ee > 99%). Electrophilic hydroxylation of 8 (-->19; Scheme 3), subsequent iodo-esterification (-->21; Scheme 4), and nucleophilic al kylation and phenylation afforded, after saponification and deprotecti on, a series of 4-substituted (2S,3R)-3-amino-2-hydroxybutanoic acids 24 including the N-terminal acids 24e (=3) and 24f (=4) of bestatin an d microginin (de > 95%), respectively.