The preparation of 1,3,2-benzodithiazole S-oxide analogs exhibiting in vitro antifungal activity against several strains of Candida is described. For the preparation of derivatives bearing aromatic substituents, a novel electrophilic aromatic thiolation reaction was utilized which produced substituted aromatic 1,2-dithiol intermediates. The reactions of nucleophiles with the parent heterocyclic system have led to an efficient transamidation process which allows for the direct production of these analogs. The S-oxide bond exhibits poor stereochemical stability and has been found to epimerize under ambient conditions. The structure-activity data report that a side chain of greater than 10 carbons effects a loss in activity as does the placement of polar groups in this chain.
Synthesis and Antifungal Activity of 1,3,2-Benzodithiazole S-Oxides.-A series of title compounds is synthesized either by cyclitive amination and subsequent oxidation, e.g. (III), or by transamination, e.g. (VI), or by a novel reaction sequence with the appropriate benzothioles as starting materials as in (X). Compared with the antifungal amphotericin B, most of the title compounds exhibit good in vivo activity against Candida strains, but a side chain of greater than 10 carbons effects a loss of activity, e.g. (IIIb), as does the placement of polar groups in this chain, e.g. (IIIc). -(KLEIN, L. L.; YEUNG, C. M.; WEISSING, D. E.; LARTEY, P. A.; TANAKA, S. K.; PLATTNER, J. J.; MULFORD, D.
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