14 マンザシジン類の全合成(口頭発表の部)

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Manzacidins isolated from Hymeniacidon sp. have attracted much attention because of their biological activities and their novel structures possessing an ester-linked bromopyrrole carboxylic acid ester, an amino group attached to the quarternary carbon center, and a tetrahydropyrimidine ring. In this report, the first total synthesis of manzacidin A, which accompanied determination of its absolute stereochemsitry, is described. The key feature to the total synthesis relies on stereoselective construction of the aminonitrile intermediate 4a by the asymmetric Strecker synthesis. To this end, three kinds of ketoamide 3a-c prepared by condensation of a chiral amino alcohol 2 with glycine, L-or D-phenylalanine were employed. Treatment of glycyl amide 3c with TMSCN and ZnCl_2 afforded a diastereomeric mixture of aminonitriles 4c and 4d in a ratio of 1:5 in 48% yield. When ketoamide 3a bearing phenylalanine as the asymmetric transferring group was used, the double asymmetric induction occurred to give 4a as a sole product. The addition reaction from 3b was also stereoselective to provide 4b in high yield. Relative stereochemistries of the Strecker adducts 4a and 4b corresponded to those of manzacidin A and C, respectively. Total synthesis of manzacidin A was achieved by the following sequence of reactions: 1) oxidation of aminonitrile 4a to imine 5, 2) hydrolysis of 5 followed by introduction of Boc protective groups to the amino groups, 3) conversion of 6 to the lactone 7, 4) formation of the tetrahydropyrimidine ring, and 5) esterification of 9 with bromotrichloroacetylpyrrole 10. The absolute stereochemistry was determined to be (4S,6R) by comparison of optical rotation of the synthetic manzacidin A with that of natural manzacidin A.
天然有機化合物討論会の論文
1999-09-01

14 マンザシジン類の全合成(口頭発表の部)

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