Total Synthesis of Biological Important Complex Molecules: (+)-Monanchorin, Akashin A, and the Convergent Synthesis of Oligosaccharides.

摘要

Since anomeric bonds play essential roles in many natural products that are biologically important, ways to establish new anomeric linkage between carbons are always of great interest to the synthesis community. Traditional approaches toward building of anomeric bonds relied on using strongly acidic conditions. In addition, poor stereoselectivity is another drawback for these traditional reactions. To address these concerns, an alternative palladium catalyzed reaction was proposed and successfully applied to address the above mentioned issues.;My first project was to synthesize the natural product, (+)-Monanchorin. This compound had been synthesized three times before via different approaches. All of the previous syntheses relied on the deprotection and ring-closing reaction in order to form the bicyclic aminal ring at the last step. Instead, we were interested in first assembling the six-membered carbon ring by using our Pd-catalyzed glycosylation, and then finishing the guanidine ring-closing reaction in the end since this natural product can be viewed as a hemiacetal.;Besides the typical O-glycosylation reactions, the Pd-catalyzed condition is also amenable to N-glycosylation. This N-glycosylation method was used in my second project toward total synthesis of Akashin A. In addition to the regular reagents used in Pd-catalyzed glycosylation, DPPB was added as an additive to catalyze the N-glycosylation between 5-chloroindole and Boc-allylic azide. The success of this N-glycosylation made us very optimistic that this reaction sequence will lead to the synthesis of Akashin A.;To demonstrate how powerful our de novo glycosylation method was, my third project focused on the convergent synthesis of trisaccharide and heptasaccharide glycosyl donors and coupling them with tyrosine peptide. In addition, a methodology for coupling oligosaccharides with simple alcohol by introducing alcohol activator was also carried out and important results were obtained. The future goal is to couple oligosaccharides with serine and threonine.