18 分子内C-グリコシル化反応を利用したpolygalolide類の合成研究(口頭発表の部)

抄録

Polygalolide A and B (Figure 1) were isolated from a Chinese medicinal plant, Polygala fallax, by Wei and co-workers in 2003. These structures indlude an oxabicyclo[3.2.1]ocate, a five-membered lactone, s six membered ether, an aromatic ring and contiguous quaternary stereo centers at the C-2 and C-8 positions. Total synthesis was reported by Hashimoto in 2006 and Snider in 2007. Although details of the biological activity have not been reported yet, polygalolides are attractive target for tatal synthesis because of the novel structure. In order to construct the congiguous quaternary stereo centers, the core structure of polygalolides, we have developed a new synthetic methodology through intramolecular C-glycocylation; siloxyfuran 4 underwent cyclization upon treatment of TiCl_4 or BF_3・OEt_2 to give the desired oxabicyclo compounds 5-A and 5-B (Table 1). Based on the above results, siloxyfuran 11 including acetylene at the C-8 position was synthesized from D-glucal in 13 steps. Treatment of 11 with TiCl_4 or BF_3・OEt_2 gave a byproduct 13 instead of a disired product 12. Further investigations led us to find that reaction of 11 with Et_3N and TBSOTf in CH_2Cl_2 afforded an oxabicyclo compound 12 as a single diasereomer in 63% yield. Reduction of unsaturated lactone of 12 was followed by radical deoxygenation at the C-3 position via xanthate 16 and then destannylation to give olefin 18. Deprotection of benzyl group, followed by oxidation gave enone 19. Further investigation toward the total synthesis of polygalolides is now in progress.