BIMANE CYCLIC ESTERS, POSSIBLE STEREOLOGUES OF TRYPANOTHIONE AS ANTITRYPANOSOMAL AGENTS - BIMANES-29

Tricyclic esters derived from bimanes have been synthesized with ring sizes near or equal to that of trypanothione disulfide (T(S)(2)), a bi s-glutathionylspermidine that is involved in regulating the thiol stat us of Leishmania and other trypanosomatids. Modest activity for many o f the compounds against Leishmania donovani with a maximum at the T(S) (2) ring size suggests that the esters act as T(S)(2) surrogates. Howe ver, no inhibition of T(S)(2)-reductase is observed for a number of th e compounds. A series of tricyclic bimane amides with structures more closely analogous to T(S)2 are inactive in biological tests, New appro aches were developed for the synthesis of the amides. The surprising e ffectiveness of the cyclic ester synthesis is explained. Acid chloride formation catalyzed by sulfides is briefly described.