85 ネオメチノリドおよび10-デオキシメチノリドの合成研究

概要

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(+)-Neomethynolide (1), the aglycone of a twelve-membered ring macrolide, neomethymycin (2), was synthesized as described below. The acetylenic intermediate (10) was prepared stereoselectively from the epoxy-ketone (6). The condensation of (-)-10 with (+)-Prelog-Djerassi lactonic methyl ester (11) afforded a mixture of the hemiacetals (12), which was transformed to the seco-acids (17 or 18) through 3 steps. Lactonization of 17 or 18 by the mixed anhydride method using 2,4,6-trichlorobenzoyl chloride gave the highly strained bicyclic lactones (19 or 20) in 12.0% and 31.7% yield, respectively. The hydrolysis of 19 and 20 followed by the deprotection gave 8,9-didehydroneomethynolide (23) in a satisfactory yield. The reduction of 23 with chromous sulfate yielded (+)-neomethynolide (1) in 65% yield. Physical properties of 1 were in good agreement with those reported for the specimen derived from natural neomethymycin. Thus these results established not only the proposed structure but also the stereochemistry of C-10, C-11, C-12 and 8,9-double bond which had remained unproved. 10-Deoxymethynolide (3), which corresponds to the aglycone of the macrolide antibiotic, YC-17, was also synthesized in the similar manner starting from (+)-Prelog-Djerassi lactonic methyl ester (11) and the (+)-acetylenic intermediate (30) which was prepared stereospecifically from (+)-epoxy ester (24).
天然有機化合物討論会の論文
1981-09-10