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Epimerization at C‐2 of 2‐substituted thiazolidine‐4‐carboxylic acids
Author(s) -
Nagasawa H. T.,
Goon D. J. W.,
Shirota F. N.
Publication year - 1981
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570180538
Subject(s) - chemistry , epimer , enantiomer , racemization , carboxylic acid , stereochemistry , thiazolidine , medicinal chemistry , lactol , organic chemistry , lactone
2( R,S )‐5,5‐Trimethylthiazolidine‐4‐(S)‐carboxylic acid ( 1a ), with a 3.3 to 1 predominance of the 2S ( cis ) isomer, was shown to epimerize at the C‐2 position in neutral, protic solvents. This was manifested by mutarotation concomitant to changes in the ratios of the C‐4 methine proton resonances in the nmr spectrum. Compound 1a was stable in dilute sodium carbonate solution, but underwent rapid equilibration in 1 N hydrochloric acid. Acetylation of 1a gave an acetyl derivative ( 2a ) with exclusively 2 S ,4 S stereochemistry. Chiral integrity at C‐2 was proved by conversion of both 2a and its enantiomer 2b via their munchnone derivatives to enantiomeric dimethyl 1,1,3,5‐tetramethyl‐1 H ,2 H ‐pyrrolo[1,2‐ c ]thiazole‐6,7‐dicarboxylates ( 4a and 4b ). Acetylation of 2‐( R , S )‐phenyl‐5,5‐dimethylthiazolidine‐4( S )‐carboxylic acid, afforded both the 2 S ,4 S ( 6a ) and 2 R ,4 S ( 6b ) epimers. Epimerization of 6a at C‐4 gave the 2 S ,4 R isomer ( 6c ) which was enantiomeric with 6b .