Total Synthesis Of Resin Glycosides

Resin glycosides which was isolated from morning glory family exhibited unique bioactivities.Especially,Murucoidin Ⅴ was represented reversal of multidrug resistance(MDR)in cancer therapy,it could enhance vinblastine activity by 255-fold in human breast cancer cells resistant to vinblastine when incorporated.Murucoidin Ⅲ-IV,Stoloniferin Ⅰ,and Mammoside A also exibited tumor cytotoxicity,antimicrobial activity and ionophoretic activity across human erythrocyte membrane,respectively.However,isolating such products from natural plants is tedious,time-consuming and scanty.Thus,it is significant to accomplish the syntheses of Murucoidin Ⅴ and its analoges through efficient chemical synthetic strategy.In this paper,based on the interrupted Pummerer reaction mediated(IPRm)glycosylation which developed by our group,we have succesfully accomplished the rapid synthesis of five resin glycosides and three derivatives.Combined with latent-active stratege,Murucoidin Ⅴ and Murucoidin IV were successfully synthesized via the same late-stage macrolactonization route.Based on that,the synthesis of Murucoidin II,Stoloniferin Ⅰ and Mammoside A were also realized with the longest linear route of 22-23 steps.The combination of IPRm glycosylation with latent-active stratege streamlined the first total synthesis of five structurally complex resin glycosides.During the syntheses,a novel site-selective macrolactonization was developed to obtain 19-membered macrolactone in the presence of multiple hydroxyl groups.It provided a powerful tool for macrolacton.Meanwhile,we found the temporary cis-diol protecting group phenyl boronic ester was compatible with the IPRm glycosylation reactions and was easily to be removed during the column chromatography.So,a single-pot transient protection-glycosylation-deprotection strategy was introduce to increase the synthetic efficiency.In conclusion,we have successfully accomplished the synthesis of various resin glycosides,which is of great significance for the bioactivity study of related resin glycosides.The successful applications of these strateges are also expected to pave the way for the synthesis of more complex natural products.