107(P-30) Macrosphelide (+)-A,(-)-A,(+)-Eの全合成(ポスター発表の部)

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(+)-Macrosphelide A (1) was isolated from the broth of Microsphaerosis sp. FO-5050 by Omura and co-workers. It has been exhibited to strongly inhibit the adhesion of human leukemia HL-60 cells to human umbilical-vein endothelial cell (HUVEC) in dose-dependent fashion. It is the first 16-membered ring antibiotics involving three lactone linkages. (+)-Macrosphelide E (2) was isolated from a strain of Periconia byssoides separated from the gastrointestinal tract of the sea hare Aplysia kurodai and was found to be the stereoisomer, in which the configuration of 3-position was different from that of (+)-Macrosphelide A (1). Recently, the absolute structures of (+)-Macrosphelide A (1) and E (2) have been determined as depicted 1 and 2 (Scheme 1). Total syntheses of (+)-1 were achieved by two groups. Our synthetic plan is different from the above-mentioned two groups as described at late in this text. We reported that the enantioselective hydrolysis of methyl (±)-(4,5)-anti-5-acetoxy-4-benzyloxy-2(E)-hexenoate (±)-3 using the lipase "Amano PS" from Pseudomonas sp. in phosphate buffer solution gave the (4R,5S)-5-acetoxy ester (-)-3 (>99%ee, 48% yield) and the (4S,5R)-5-hydroxy ester (+)-4 (>99%ee, 44% yield), and methanolysis of (4R,5S)-3 provided the (4R,5S)-4 in 90% yield. The key steps of our synthetic strategy of (+)-1 and (+)-2 are the enantioselective preparation of two differentially protected (4R,5S)-4-benzyloxy-5-hydroxy-2(E)-hexenoic acid congeners, carboxylic acid (4R,5S)-5 and alcohol (4R,5S)-6 from (4R,5S)-4, and regioselective ester formation from (4R,5S)-5 and (4R,5S)-6. The third building blocks, (S)- and (R)-3-hydroxybutanoic acid derivatives 9 derived from commercially available (S)- and (R)-3-hydroxybutanoate are separately coupled with (-)-8 to give (-)-10 and (-)-25, respectively. Then, after regioselective deprotection of 2,2,2-trichloroester group, the generated seco acids 12 and 27 were subjected to macrolactonization to afford (-)-13 and (-)-28, respectively, which were debenzylated to afford (+)-Macrosphelide A (1) and E (2) respectively. In the same manner, synthesis of (-)-Macrosphelide A was also accomplished.
天然有機化合物討論会の論文
2000-10-01

107(P-30) Macrosphelide (+)-A,(-)-A,(+)-Eの全合成(ポスター発表の部)

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