Premium
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)
Author(s) -
Griesbeck Axel G.,
Hirt Joachim,
Peters Karl,
Peters EvaMaria,
von Schnering HansGeorg
Publication year - 1995
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199519950486
Subject(s) - chemistry , diastereomer , cycloaddition , ring (chemistry) , stereochemistry , absolute configuration , valine , yield (engineering) , derivative (finance) , 1,3 dipolar cycloaddition , photoisomerization , chiral auxiliary , amino acid , organic chemistry , enantioselective synthesis , isomerization , biochemistry , materials science , economics , financial economics , metallurgy , catalysis
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 ).