Synthesis of Biologically Active Nonnatural Palmarumycin Derivatives

Abstract

AbstractDiels–Alder reaction of benzoquinone monoacetal 1 with 1‐methoxy‐1,3‐butadiene (4) and dimethyl(1‐methyl‐3‐vinylcyclohex‐3‐enyl)(phenyl)silane (5) gave the expected adducts 2 and 3, whereas with siloxy‐dienes such as 3‐methyl‐1‐(trimethylsiloxy)‐1,3‐butadiene (6) a 1,2‐aldol‐type adduct 9 was isolated. The Diels–Alder adduct 2 was isomerized under mild basic conditions to the olefin 10 and eliminated to the diene 11 under mild acidic or thermal conditions. The olefins 2, 10 and 11 were subjected to epoxidation with m‐chloroperbenzoic acid and tert‐butyl hydroperoxide under mild basic conditions to afford the epoxides 12, 15, and 18 under the former conditions and 13, 14, 16, 17, 19, and 20 under the latter conditions. The olefins 1, 2, 10, 11, and 20 were also transformed into the respective cis‐diols 21a and 23a–26a. From theses diols the corresponding diacetates (b) andacetonides (c) were prepared. The compounds were tested against the Gram‐negative bacterium Escherichia coli, the Gram‐positive bacterium Bacillus megaterium, and the fungus Microbotryum violaceum. Whereas compound 25b was the most active of the diacetates and the epoxide 18 the most active of all substances, all of the compounds were biologically active against the three test organisms, equalling and surpassing those of the natural palmarumycins.