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)

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