ORGN 267 |
| Given the fundamental role exerted by the glycan moiety in natural O- and N-linked glycoprotein structural and functional roles, the cotraslational synthesis of selectively glycosylated unnatural analogues displaying an anomerically linked spacer resistant to chemical and enzymatic hydrolysis offers a wide range of opportunities. These include the development of probes for studies of biological pathways and the design of modulators of recognition processes responsible of both detrimental (viral and bacterial infections, cancer metastasis) and beneficial ( immune response, fertilization) events. To this aim, new families of carbon-linked glycosyl amino acids have been prepared, all featuring an aromatic heterocycle tether holding the carbohydrate and the glycinyl moieties. In addition of being a stable scaffold, the rigid heteroaromatic group of these amino acids may induce improved physicochemical properties and bioavailability of peptides in which they are incorporated. Two ligation approaches with high levels of chemical efficiency were employed. The first, reported few years ago (Org. Lett. 2004, 6, 2929) exploits the 1,3-dipolar cycloaddition chemistry of nitrile oxides and azides with alkynes to give isoxazole- and triazole-linked glycosyl amino acids; the second employs the multicomponent Hantzsch reaction (aldehyde, ketoester, enaminoester) affording compounds in which the heterocycle scaffold is constituted by the pyridine group. Elements of diversity in the latter family of sugar amino acids are the structure and anomeric configuration of the glycosidic fragment and the position of attachment to the heterocyclic ring. |
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Asymmetric Syntheis of α-Amino Acids: Novel Developments and Future Directions
1:00 PM-5:40 PM, Monday, March 26, 2007 McCormick Place Lakeside -- Room E350, Level 3, Oral
Division of Organic Chemistry |