44 Synthetic Studies on Naturally Occurring Diolides
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Naturally occurring antibiotic macrodiolides, pyrenophorin (1), vermiculine (2), and colletallol (3), were synthesized in their racemic forms from the corresponding hydroxycarboxylic acids (16), (23), and (44) respectively via stereoselective formation of the requisite trans double bonds after macrocyclization. Pyrenophorin (1): Hydroxycarboxylic acid (16) readily prepared from glycol (8) was subjected to lactonization to give rise to diolide (17) in 60% yield which was converted to the bis trans α,β- unsaturated lactone (11) in the desired sence. Colletallol (3): The method was further applied to the synthesis of the non-symmetric diolide colletallol (3). Lactonization of (23) by treatment with diethyl phosphoro-chloridate followed by exposure to a solution of acetonitrile in the presence of catalytic amounts of DMAP gave diolide (24) in 90% yield, which was transformed to dl-colletallol (3) under the same procedures. Vermiculine (2): Oxidation of selenide (30) furnished cis diolide (32) as the only observed product in 86% yield. These results were completely different from those of trans stereoselection observed in the case of pyrenophorin and colletallol syntheses. Consequently, dl-vermiculine (3) was synthesized via oxidative elimination of (45) followed by oxidation of (46) and deketalization of (47) with trifluoro-acetic acid.
