Total Synthesis Of Solasonine And(22S, 25R)-α-Solanine

Solasonine and a-solanine are glycoalkaloids isolated from Solanum nigrum. It has been reported that solasonine is active to malignant skin tumors and a-solanine shows inhibition to human cervical HeLa cells, HepG2 cells, lymphoma U937 cells at some extent. (22S,25R)-α-Solanine,22S and 25R epimer of a-solanine, may have potential pharmacological activities too. At present, the separation of glycoalkaloids from natural products are difficult and low in yeilds, which limited their further research. Chemical synthesis is a useful way to overcome this issure.Currently, few synthetic methods for solasonine and (22S,25R)-α-Solanine has been reported. The known protocols for glycoalkaloid syntheses mainly adopt linear synthesis strategy using bromo glycoside or thioglycoside as a donor, which resulted in low efficiency. In this paper, we take solasonine and (22S,25R)-α-Solanine as target molecules. To achieve their total syntheses, we made use of diosgenin, D-galactose, D-glucose, L-rhamnose as starting materials and explored the following two strategies:1. Linear synthetic strategy:The glycosylation of diosgenin with acyl protected galactosyl trichloroacetimidate to generate monosaccharide. Then stepwise enlongation of sugar chain to furnish solatriosyl glycoside. Lastly, to complish the conversation of trisaccharides glycoside to solasonine and (22S,25R)-α-Solanine, we exploited E/F ring opening mediated by oxone, introduction of nitrogen nucleophiles 26-position and its subsequent reduction. Unfortunately, this strategy failed.2. Convergent synthetic strategy:By means of boron trifluoride etherate mediated E/F ring opening, azide formation at 26 position followed by Lindlar catalyst catalyzed hydrogenation and subsequent reductive amination with sodium cyanoborohydride, the transformation of diosgenin to solasodine and (22S, 25R)-α-Solanidine were accomplished with the longest linear 7-and 9-step reactions in overall yields of 38% and 20%, respectively. Making use of D-galactose, D-glucose, L-rhamnose as starting materials, solatriosyl trichloroacetimidate was prepared in 17% yield through the necessary group protection. The coupling reactions of solasodine and (22S,25R)-α-Solanidine with the solatriosyl trichloroacetimidate in the respective promotion of HB(C6F5)4/H2SO4-SiO2 and HB(C6F5)4 to finish the corresponding glycosides in yields of 82% and 98% with high β glycosidic bond selectivity. Final global removal of the acyl protecting groups furnished solasonine and (22S,25R)-α-Solanine. This work provide substances for the investigation into structure-activity relationships and mechanism of action of solasodine and (22S,25R)-α-Solanidine. And it is significantly interesting to the syntheses of other spirosolan and solanidan glycoalkaloids.