Synthesis of isoaspertetronin, isogregatin and related O-methyltetronic acids. Reassignment of 5-methoxyfuran-3(2H)-one structures to the aspertetronin group of natural products

Abstract

Reaction between (3E,5E)-octa-3,5-dien-2-one and the vinylic anion (10) derived from (9) leads, in one step, to the O-methyltetronic acid (12). The tetronate (12) was also obtained by treatment of the lithium anion derived from ethyl propiolate with the octadienone (11), followed by reaction of the resulting hydroxyester (17) with methanolic sodium methoxide.

Metallation of the O-methyltetronic acid (12), followed by treatment of the resulting C-2(α-)-vinylic anion (19) with methyl acetate and methyl (E)-butenoate then gave the acylated O-methyltetronic acids (20) and (22) respectively. The O-methyltetronic acids (20) and (22) are shown, by comparison of physical and spectroscopic data, to be enol ether isomers of the natural products gregatin B and aspertetronin A found in Aspergillus sp. and Cephalosporium gregatum.

The aspertetronin (also known as gregatin and graminin) group of natural products are all shown to have the 5-methoxyfuran-3(2H)-one structure (25) rather than the previously assigned O-methyl tetronic acid structure e.g.(1). We propose the names isoaspertetronin and isogregatin B for the synthetic O-methyltetronic acids (22) and (20) respectively.