Study On The Synthesis Of Sugar Amino Acids Used As Building Blocks For Oligosaccharide Mimetics

To meet the growing demands for the development of new molecular entities for discovering new drugs and materials, organic chemists have started working on many new concepts that can help to assimilate knowledge-based structural diversities more efficiently than ever before. Emulating the basic principles followed by nature to build its vast repertoire of biomolecules, organic chemists are developing many novel multifunctional building blocks and using them to create ‘nature-like’ and yet unnatural organic molecules.Sugar amino acids(SAAs) are carbohydrate derivatives bearing amino groups, carboxylic acids as well as hydroxyl groups. These three functional groups provide an excellent opportunity for organic chemists to create structural diversities for unnatural SAAs molecules. SAAs possess structural and functional characteristics of both sugar and amino acid and can be used as multifunctional synthetic building blocks for studying combinatorial chemistry, building glyco-mimetics and peptide mimetics. These synthetic SAAs also can be used as starting points for preparing different oligomers. They are potential pharmaceutical compounds and are valuable for the synthesis of natural products or analogues. They are also used as building blocks in drug design and drug research.Therefore, the design and synthesis of SAAs were concerned sustainably by chemist from domestic and abroad.In our research, we developed a simple and efficient method for the synthesis of novel SAAs and used them as building blocks for synthesizing homologous and heterologous linear dimer, tetramer and octamer oligosaccharide mimetic by polymerization reaction. Firstly, we use a convenient and versatile radical reaction starting from glycals in the presence of cerium(IV) ammonium nitrate(CAN) to obtain 2-C-branched carbohydrates, which could be used as the synthetic precursor of SAAs. To gain access to the required C-2 branched-chain glycosamines, the nitro group had to be reduced and benzyl had to be deprotected by Pd/C. Boc-protected amino intermediate were obtained after react with Boc2 O. Then after through selectively protecting C-6-hydroxyl group with TIPSCl, protecting the C-3 and C-4 hydroxy group with Bn, deprotecting C-6-O-TIPS and finally oxidation we afforded the gluco-SAA and galacto-SAA. In order to optimize the reaction yield, we have designed another synthetic route to obtain target products. After a key step, SAAs were achieved through selective debenzylation–acetylation of perbenzylated radical addition products using Zn Cl2-Ac2O-HOAc. The yield of gluco-SAA was increased from 14.3% to 20.4% and galacto-SAA was increased from 4.7% to 7.4%. A series of glycopeptide polymer, nine kinds of homo and hetero-linear dimeric, tetrameric and octameric oligosaccharide mimetics, were efficiently synthesised by simple polymerisation of the obtained SAAs unit with diphenylphosphoryl azide(DPPA) as a convenient promoter. Finally, we use NMR and TOF mass spectrometry to analyze the structure and conformation of glycomimetics for further research.