Basidalin

Butenolides and tetronic acids occupy a prominent position in synthetic chemistry due to their ubiquitous distribution in nature. This has stimulated investigations firstly in the synthesis of such systems and, laterly, the interest has turned to the understanding of the quantum structure of such systems, allowing a deeper understanding of the mechanism and reactivity of this cyclic scaffold. In contrast, tetronamides, which consist of compounds bearing a 4-aminofuran-2(5H)-one backbone, are relatively rare in nature and synthetic routes to such compounds are poorly explored. This review highlights both the importance of the tetronamide scaffold in medicinal chemistry and the most relevant recondite synthetic strategies for obtaining compounds of this class.

Two antibiotic metabolites were isolated from cultures of Leucoagaricus carneifolia. Their structures were elucidated by spectroscopic methods. The first compound, 7-chloro-4,6-dimethoxy-1(3H)-isobenzofuranone [corrected] (1) had to our knowledge not been described from natural sources whereas the second, basidalin (2), is a known metabolite of L. naucina (H. Iinuma et al., 1983). 1 exhibits antibiotic activities with minimal inhibitory concentrations of 20 micrograms/ml against Botrytis cinerea, the most sensitive microorganism.

The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-β-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.