1 天然マクロライド類の全合成研究(口頭発表の部)

抄録

We show here synthetic studies on halicholactone (1), solandelactones (2) and cineromycin B (3) using our chiral building block 6 or 34 as a starting material. Halicholactone (1) was isolated from the marine sponge, Halichondoria okadai, and inhibits 5-lipoxygenase of guinea pig polymorphonuclear leukocytes. Recently, we achieved total synthesis of 1 from 6. The starting material (6) was converted into 5 through an epimerization of 9. A key reaction, NHK reaction of 5 with 15, proceeded in DMSO/DMF solution to afford 16a preferentially. Another key reaction, RCM reaction of 4 which was derived from 16a, gave nine-membered lactone. Finally, methanolysis of two acetates afforded 1. We also tried to synthesize 2, which was isolated from the hydroid, Solanderia secunda, and inhibit farnesyl-protein transferase, using the same key reactions. We have now succeeded in synthesizing 18 by RCM reaction of 9 which was derived from 12. Transformation of 18 to 2 is now in progress. Cineromycin B (3) is a macrolide antibiotic isolated from various strains of Steptomyces sp. and displays biological activity primarily against B. subtilius and S. aureus. Very recently, a new activity that 3 induces apoptosis of tumor cells was taken an interest. These important activity and unique structural features have inspired us to its synthesis. Now we show a total synthesis of 3 using oxidative [2.3]-sigmatropic rearrangement of 40 as a key reaction. Firstly, we synthesized 40 from our chiral building block 34. The key rearrangement of 40 was achieved successfully by treatment with H_2O_2 at 0℃ to give 41. Macrocyclization of 30 derived from 41 was unsuccessful and gave 42. In order to afford the desired ring system, protection of the tertiary hydroxyl group was essential and cyclization of 44 gave 45. Finally, we accomplished the total synthesis of 3 by deprotection of TES group.