Efficient asymmetric synthesis of (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine using camphorsultam as a chiral auxiliary.
(1R)-(+)-2,10- and (1S)-(-)-2,10-camphorsultam were acylated with ethyl 2-phenylthiazoline 4-carboxylate to afford (+)- and (-)-2-phenylthiazolinylcamphorsultam, which were stereoselectively alkylated with MeI in the presence of n-BuLi. Alkylation of these phenylthiazolinylcamphorsultams occurred from the beta-face rather than alpha-face, resulting in the formation of (S)-alpha-methylcysteine from (1R)-(+)-2,10-camphorsultam and (R)-alpha-methylcysteine from (1S)-(-)-2,10-camphorsultam after acidic hydrolysis. Subsequent protection of the side chain thiol group with trityl alcohol and alpha-amine function with Fmoc-OSu furnished fully protected (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine in overall 20% yield.
Singh
Satendra
S
Bachem Bioscience Inc, 3700 Horizon Drive, King of Prussia, Pennsylvania 19406, USA. ssingh@usbachem.com
Rao
Samala J
SJ
Pennington
Michael W
MW