Conversion of L-Cysteine into D-α-Amino Acids and Related Transformations

Naturally configured cysteine is converted into 4-substituted thiazolidines via the 4-carbaldehyde corresponding to the serine derived Garners aldehyde. The key transformation is the conversion into 5-thiazolidinones by O-1(2) oxidation, and fragmentation of the primary 5-hydroperoxides under in situ acetylating conditions. Whereas the reagent couple trimethylsilyl halides/phenol selectively cleaves the N-Boc group, LiOH/H2O2 transforms the thiol lactones into lactones by an unknown mechanism, and, subsequently, also cleaves the acetonide affording N-Boc-protected D-amino acids without loss of optical activity. This sequence tolerates unsaturated residues with sensitive allylic functions. In some cases, double bond isomerization is, however, observed. The thiazolidine intermediates can be cleaved with 3-nitro-2-pyridinesulfenyl chloride, giving reactive mixed disulfides.