Synthesis of natural and non natural orthogonally protected lanthionines from N-tritylserine and allo-threonine derivatives

The reactivity of electrophiles derived from N-tritylserine, threonine and allo-threonine esters toward a selection of nucleophiles was investigated. Best yields from substitution products were obtained with N-trityliodoalanine and soft nucleophiles such as thiols. This strategy was applied to the synthesis of lanthionines, the monosulfide analogs of cystine. Orthogonally protected sulfide adducts from L- and D-cysteines, threo-beta-methyl-L-cysteine and D-penicillamine were isolated in 81-88% yield (ee>98%). This strategy was applied to the preparation of lanthionine and cyclolanthionine suitably protected for peptide synthesis. (C) 1997 Elsevier Science Ltd.