44 メチノライドの合成

概要

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Methynolide (1), the aglycone of a macrolide antibiotic, methymycin (2), was synthesized via its 8,9-didehydro derivative (27), as described below. The acetylenic intermediate (13) was synthesized starting from the optically active dihydroxy acid (3) through the acetonide aldehyde (5). The Prelog's lactone (18) was obtained starting from meso-2,4-dimethylglutaric anhydride (14) in six steps including the separation procedures, in 11.6% overall yield. The methyl ester (19) of the resolved 18 was transformed into the acid bromide (21) in which the hydroxy group was protected by chloroacetyl group. Condensation of 21 and the silver salt of 13 led to 22 which was then converted into the seco-acid (24) by successive reduction, deprotection, reprotection, and hydrolysis. For the lactonization of 24, a newly developed procedure in which the mixed anhydride of a hydroxy acid and 2,4,6-trichlorobenzoic acid was treated with dimethylaminopyridine in refluxing benzene, was used. This procedure had been proved to be effective for the large ring lactonization of an acid-sensitive hydroxy acid such as 7. The acetylenic lactone (25) thus obtained was then deprotected, oxidized, and reduced to give 1, which showed the same properties as reported for the specimen derived from natural methymycin (2).
天然有機化合物討論会の論文
1978-08-22