Synthesis of α-amino-3-chloro-4,5-dihydro-5-methyl-5-isoxazoleacetic acid, a ring-methylated analogue of the antitumor agent acivicin (AT-125)

✍ Scribed by Griesbeck, Axel G. ;Hirt, Joachim ;Peters, Karl ;Peters, Eva-Maria ;von Schnering, Hans-Georg

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 627 KB
• Volume: 1995
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199519950486

✦ Synopsis

Acivicin / Photochemistry / 1,3-Dipolar cycloadditions / Jitrile oxi, .es a-Amino-3-chloro-4,5-dihydro-5-methyl-5-isoxazoleacetic involving the photoisomerization of N-phthaloylvaline acid (8), a ring-methylated analogue of the potent antitumor methyl ester (1). The stereochemical course of the 1,3-dipolar agent acivicin (AT-125), is synthesized in a 6-step procedure cycloaddition is proven by means of a X-ray structure analyin 63% overall yield from (S)-valine. Key step is the 1,3-dipo-sis of the major diastereoisomer ?a formed in the chloronitrile lar addition of bromonitrile oxide to the N,C-protected (S)-oxide cycloaddition. The absolute configuration of the major isodehydrovaline (6) available from (S)-valine in four steps ( u ) diastereomer ?a and the bromo derivative 7b is (aS,5R).

Acivicin

or AT-125, (crS,.5S)-a-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (Figure l), has been isolated by Martin et al.['l from fermentation broths of streptomyceus sviceus and characterized as an antimicrobial, antimetabolic and effective antitumor agent[*].