Studies On The Total Synthesis Of Antibiotic Tunicamycin And The Gold(â… )-Catalyzed Giycosylation Reaction

1. Synthetic studies towards the tunicamycinsTunicamycins is a group of nucleosides with potent antibiotic and antiviral activities. A facile, stereoselective synthesis of Tunicamycin V is described. Within this synthetic route, an efficient method for carbon-carbon bond formation was developed, involving stannic chloride(SnCl4) mediated Mukaiyama aldol reaction and gold(â… )-catalyzed glycosylation. The protocol of aldol reaction forms the basis for the stereoselective preparation of tunicamine, which contains a C—C linkage between two sugar units. Our route integrates a stereoselective synthesis of the intriguing α,β-trehalose glycosic bond and a surprisingly facile and highly diastereoselctive late-stage N-glycosylation, using ortho-alkynylbenzoates as donors.2. Total synthesis of simplexides and congenersSimplexides constitute a unique group of immunosuppressive glycolipids that demonstrate antiproliferative activities against activated T-cell lymphocytes via a unique non-cytotoxic inhibition. We have developed an efficient and divergent route to the synthesis of simplexides and congeners, taking advantage of a late-stage olefin cross-metathesis reaction. A library of glycolipids with structural alternation in the lipid moieties has been successfully synthesized and characterized. The determination of the biological activities of these glycolipids is in progress.3. Mechanistic aspects of gold(I)-catalyzed glycosylation with glycosyl ortho-alkynylbenzoates as donors involve the vinylgoldoxonium intermediate and glycoside anomerizationThe gold(â… )-catalyzed glycosylation reaction with orttho-alkynylbenzoates as donors has recently been proven to be a versatile method for the synthesis of various glycosidic linkages, including remarkably those vulnerable to acidic conditions. We studied in details the gold(â… )-catalyzed transformation of orttho-alkynylbenzoates in the absence of acceptor, that is disclosed to be mainly the anomerization. The proposed key intermediate in the anomerization, a transient glycosyloxypyrylium species, is successfully trapped via a cycloaddition reaction with n-butyl vinyl ether as a dienophile. These findings have enabled us to further elaborate and applicate our new efficient glycosylation method.4. Highly stereoselective synthesis of heparin oligosaccharides via gold(â… )-catalyzed glycosylationHeparin and heparan sulfate, play important roles in many biological events, such as blood coagulation, angiogenesis, lipid metabolism, growth factor binding, cell adhesion, inflammatory response and viral infections. They are composed of repeating disaccharide units of1â†'4linked uronic acid and D-glucosamine. Herein, we report a highly selective glycosylation for the synthesis of GlcN-a-(1â†'4)-GlcA/IdoA oligosaccharides, employing2-azido-glucopyranosyl orttho-hexynyllbenzoates as donors.