Uncommon Amino Acids in the Strategy of Natural Product Synthesis

Abstract

The chemistry of amino acids occuring in proteins is well established. Much less is known, however, about amino acids that occur in lower organisms and that have a functionality in addition to the amino and carboxy group. A pathway linking protein amino acids and uncommon, non-protein amino acids deserves attention as an outline of a biological relationship between these amino acids as well as a «chemosynthetic chart». This is illustrated by a biogenetic approach to gliotoxin and sporidesmin B; our approach features the transposition of a N-hydroxy group to a α-functionality in amino acids. Some novel reactions with a cycloadduct from indole derivatives and nitroso olefins open a new approach to indole alkaloids, e.g. tryptathionine, both in terms of strategy and methodology. Finally, one of our syntheses of sparsomycin is outlined. This bacterial metabolite contains a monooxodithio-acetal moiety which can be considered as a derivative of D-cysteine. Consequently, our approach features nucleophilic ring-opening of the sultine prepared from D-cysteine. Structure-activity relationship studies of sparsomycin have resulted in the synthesis of two analogues that have a higher antitumor activity and a lower toxicity than sparsomycin itself.