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

点击翻译按钮获取中文摘要

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.