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Studies on the Synthesis of Biologically Active Saponins Capitalizing on Phosphurus-Containing Leaving Groups

利用含磷离去基团合成生物活性皂苷的研究

基本信息

批准号：
18590001
负责人：
NAKAMURA Seiichi
金额：
$ 2.57万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

At the outset of our work, glycosylations of silyl ethers were investigated using donors carrying phosphorus-containing leaving groups. We found that a TMS ether reacted with a per-O-benzoylated glucosyl diphenyl phosphate, phosphinimidate and phosphorodiamidate in the presence of TMSOTf at 0 ℃ to give the corresponding β-glucoside in good yields, whereas no reaction occurred with a per-O-pivaloylated glucosyl diethyl phosphite. Based on these results, following experiments were performed to develop a two-directional glycosidation strategy capitalizing on phosphorus-containing leaving groups. Glycosidation of the glucosyl diethyl phosphite with methyl 2,3-di-O-benzyl-6-O-TBS-α-glucoside proceeded BF_3・Oet_2 to furnish the anticipated disaccharide in 75% yield without concomitant loss of TBS group. The TBS ether was glycosylated with a per-O-benzoylated glucosyl diphenyl phosphate to provide a branched trisaccharide. On the other hand, a linear trisaccharide could be obtained by the use of 6-O-TBDPS-protected glucosyl diethyl phosphite as a donor, followed by reaction with a per-O-benzoylated glucosyl diphenyl phosphate.To demonstrate the synthetic utility of the developed method, we next addressed the synthesis of saponin scillascilloside E-1. Glycosidation of 2-O-pivaloyl-3-O-TBS-4,6-O-benzylideneglucosyl diethyl phosphite with a 2-O-unprotected arabinoside occurred in the presence of BF_3・Oet_2 in CH_2Cl_2 at 0℃ to give the (β-disaccharide in 80% yield. Reductive removal of the pivaloyl group was followed by TBSOTf-promoted glycosylation with a per-O-benzoylated rhamnosyl diethyl phosphite in CH_2Cl_2 at -40 ℃, affording the corresponding trisaccharide in good yield. Finally, the resultant trisaccharide TBS ether was successfully glycosylated with a per-O-benzoylated glucosyl diphenyl phosphate by using TMSOTf as a promoter, thus completing the synthesis of the tetrasaccharide unit of scillascilloside E-1.

在我们工作开始时，使用携带含磷离去基团的供体研究了甲硅烷基醚的糖基化。我们发现，在TMSOTf存在下，TMS醚在0℃下与全O-苯甲酰化葡萄糖基二苯基磷酸酯、亚膦酰亚胺酯和二酰胺磷酸酯反应，以良好的收率生成相应的β-葡萄糖苷，而与全O-新戊酰化葡萄糖基亚磷酸二乙酯没有发生反应。基于这些结果，进行了以下实验以开发利用含磷离去基团的双向糖苷化策略。葡萄糖基亚磷酸二乙酯与甲基 2,3-二-O-苄基-6-O-TBS-α-葡萄糖苷的糖苷化继续进行 BF_3·Oet_2，以 75% 的产率提供预期的二糖，而不会同时损失 TBS 基团。 TBS醚用全O-苯甲酰化葡萄糖基二苯基磷酸酯糖基化以提供支链三糖。另一方面，通过使用6-O-TBDPS保护的亚磷酸葡萄糖二乙酯作为供体，然后与全O-苯甲酰化葡萄糖二苯基磷酸酯反应，可以获得线性三糖。为了证明所开发方法的合成实用性，我们接下来讨论了皂苷scillascilloside E-1的合成。在 BF_3·Oet_2 存在下，CH_2Cl_2 中，0℃，2-O-新戊酰基-3-O-TBS-4,6-O-亚苄基葡萄糖基亚磷酸二乙酯与 2-O-未保护的阿拉伯糖苷发生糖苷化，得到 (β-二糖，收率 80%。还原去除新戊酰基团，然后 TBSOTf在-40℃的CH_2Cl_2溶液中促进全O-苯甲酰化亚磷酸鼠李糖基二乙酯的糖基化，以良好的收率得到相应的三糖。最后，利用TMSOTf作为催化剂，成功地将所得三糖TBS醚与全O-苯甲酰化葡萄糖基二苯基磷酸酯进行糖基化。启动子，从而完成scillascilloside E-1四糖单元的合成。