Design, Synthesis And Bioactivity Of New C-Glycosides Of Glyceroglycolipid Analogs

Glycolipids are important components of mammalian cell membranes and play an important role as signal mediators in cellular biology. The focus after protein and nucleic acid has been a resurgence of glycolipid derivatives in the biochemical and biomedical research field. Manny designed and isolated glycolipids and their analogs that block cell adhesion and regulate the immune response have highlighted potential therapeutic uses in the treatment of cancer, infection and other diseases originating in cell regulation disorder. To seek for more active and stable glyceroglycolipid analogs, in this work, we designed a series of new analogs of MGMG, MGDG, and SQMG.1. Glyceroglycolipids were reported having anti-tumor-promoting, oxygen scavenging, virus neutralizing, anti-hyperlipidemic and platelet aggregation inhibitory activities, which in particular, MGMG are good inhibitors of DNA polymerase and could also be human cancer chemotherapy agents. During the last two decades, C-glycosides have been recognized as stable analogs of O-glycosides because of their insusceptibility to enzymatic degradation due to the stability of glycosidic C-C bond under normal physiological conditions. Therefore, a series of novel glyceroglycolipids C-glycosides analogs bearing the propanediol backbone were designed.2 Novel designed stable glycolipid analogs have been synthesized by new and efficient routes, through stereoselective allylation of acetyl protected D-galactose and D-glucose, followed by oxidation using mild alkaline KMnO4, selective esterification using DCC and DMAP and deprotection using hydrazine in 85% aq. ethanol. Using theses roads 52 compounds including 41 new ones were synthesized in all.3. The cytotoxic activities of the synthesized compounds were evaluated by MTT tetrazolium dye assay. MGMG analogs are active as inhibitors of Hela cells. Compound 18 is the best with IC50 values of 57μg/mL However, compounds deacetylated from MGMG analogs have no obvious activity (IC50>100μg/mL), probably due to the lack of certain acetyls from Gal residue which are presumably devoting positive effect. MGDG analogs, lacking in the essential OH groups from the propanediol backbone showed a sharp decrease in activity (no inhibition was observed at 100μg/mL). This study thus indicates several important structural elements involved in Hela cells-ligand interactions and provides a brand new orientation to the development of novel galactoglycerolipid analogs.4 The mechanisms of key steps were discursion. In this paper, Lewis acids were used to synthesize C-glycosides directly and the synthesis of 3- tetraacetate-1-propylene under different reaction was investigated at the present of different Lewis acid. Different reaction conditions including temperature and the eq. of hydrazine hydrate was investigated. The process of allylation and hydrazinolysis were optimized. The proper solvent was discussed in detail, in this paper, during isolation of the hydrazinolysis reaction mixture using column chromatography.