Synthesis of orthogonally protected (R)- and (S)-2-methylcysteine via an enzymatic desymmeterization and Curtius rearrangement.
A synthesis of differentially protected (R)- and (S)-2-methylcysteines is described. Monomethylation of dimethylmalonate followed by alkylation with tert-butylchloromethyl sulfide gave an achiral diester. Desymmeterization by selective hydrolysis of one ester with pig-liver esterase gave the acid in 97% chemical yield and 91% enantiomeric excess. Heating this acid with diphenylphosphoryl azide followed by 4-methoxybenzyl alcohol gave protected (R)-2-methylcysteine. Alternately, the acid and ester groups were interchanged and heated with diphenylphosphoryl azide followed by 4-methoxybenzyl alcohol, giving protected (S)-2-methylcysteine.
Kedrowski
Brant L
BL
Department of Chemistry, University of Wisconsin-Oshkosh, 800 Algoma Blvd., Oshkosh, Wisconsin 54901, USA. kedrowsk@uwosh.edu
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000138:chemical synthesis*; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine
C008425:S-methylcysteine; D003545:Cysteine