89(P-12) イオノフォア抗生物質ジンコフォリンの立体選択的全合成(ポスター発表の部)

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Zincophorin (1) isolated from a strain of Streptomyces griseus is the unique ionophore antibiotic having a very high affinity of Zn (II) cations. Toward the total synthesis of zincophorin (1), we designed the synthetic strategy based on our original acyclic stereocontrol. Namely, zincophorin (1) was disconnected at the C15-C16 bond and divided into the segments A (2) and B (3), and both segments were stereoselectively synthesized as follows. Segment A (2) was highly stereoselectively synthesized according to Schemes. Thus, the crucial S_N2' methylation reaction of cis-epoxy unsaturated ester 9 occurred stereospecifically by the use of a new Me_2Zn-CuCN reagent in DMF, giving rise to the desired product 8 quantitatively. After 8 was converted to lactol 6, the key allylation reaction of 6 with (R)-allylsilane 5 was performed in the presence of a Lewis acid resulting in the formation of 4a and 4b, each as a single stereoisomer. Conversion of 4a to epoxy unsaturated ester 24 and subsequent methylation reaction of 24 by the Me_3Al-water system occurred highly stereoselectively to furnish 25 as a single product. After conversion of 25 to 28, the primary alcohol was oxidized to carboxylic acid, which was then treated with 9-BBN. Thus, segment A (2) having ten stereogenic centers was straightforwardly and highly stereoselectively synthesized by using original acyclic stereocontrol. On the other hand, segment B (3) was synthesized as follows. Unsaturated β-epoxy alcohol 33 derived from the same starting material was treated with the Gilman reagent to afford the S_N2' methylation product 34 as a single product. After protection of the secondary hydroxyl group in 34, the product was transformed into segment B (3) by a four-step reaction sequence involving the Takai reaction in 54% overall yield. The crucial Suzuki coupling of 2 and 3 was successfully performed to give rise to the targeted compound 35 in 69% yield. Finally, removal of all silyl groups in 35 and subsequent hydrolysis of methyl ester provided zincophorin (1) quantitatively. All the spectral data of the synthetic compound were identical with those of natural zincophorin. Thus, we have achieved the first and highly stereoselective total synthesis of zincophorin based on our original acyclic stereocontrol.
天然有機化合物討論会の論文
2004-10-01

89(P-12) イオノフォア抗生物質ジンコフォリンの立体選択的全合成(ポスター発表の部)

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