TOTAL SYNTHESIS OF ALPHA-AMINO-3-CHLORO-4,5-DIHYDRO-5-ISOXAZOLEACETIC ACID (AT-125), AN ANTI-TUMOR ANTIBIOTIC

Recently Martin el al.1 described the isolation and structure of a novel antitumor antibiotic, (αS.5S)-α-amino-3-chloro-4, 5-dihydro-5-isoxazoleacetic acid (1, AT-125). This material, isolated from Streptomyces sviceus, significantly increased the lifespan of tumor (L-1210or P388) bearing mice2 and, of even greater interest, it significantly increased the life span of immune deficient mice implanted with a solid human mammary tumor.3 The biological activity of this material and its novel structure have already elicited a report by Baldwin et al. on an approach to its synthesis which produced nonstereo-specifically a methylated analogue.4 We report here a stereoselective, total synthesis of the raccmic and optically pure isomers of AT-125.© 1979, American Chemical Society. All rights reserved.