Studies On The Stereoselective Reactions Using O-Pivaloylated-D-glucopyranose As Auxiliary And Their Application In Organic Synthesis

With people's further and further understanding for the important physiological function and potently pharmacological activity of complicated enantiomer molecules, the asymmetric synthesis has been developed rapidly and been a subject of intense research activity. Using chiral auxiliaries for the asymmetric synthesis is one of the most popular and practical methods. Carbohydrate not only exists widely in nature, but also is more accessible, inexpensive and environmentally friendly, which has been determined to be a valuable and effective chiral auxiliary for asymmetric synthesis.Herein we reported the novel methods for the stereoselective syntheses or syntheses of a-amino acids, β, γ-unsaturated α-amino acids, levetiracetam, α-amino selenides and aiylacetic acids, using glucose and its derivatives as the auxiliaries. The research results are summarized below:1. The Strecker reaction of TV- (2, 3, 4, 6-tetra-O-pivaloylated-D-glucopyranosy-l)aldimine and its stereoselectivity are studied in detail. The effects of solvents, reaction temperature, catalysts, ligand etc. for the stereoselectivity of the Strecker reaction are investigated and a new method for the stereoselective synthesis of enantiomerical a-amino acids has been developed, which has the advantages of high yields and high diastereomers' ratios and the glucopyranosyl moiety could be reused by reclaiming.2. The rupture of N-C bond of N-(2, 3, 4, 6-tetra-O-pivaloylated-D-glucopyrano-syl)-a-amino nitrile has been investigated in detailed, which provided a novel method for the synthesis of arylacetic acids using 2, 3, 4, 6-tetra-O-pivaloylated-D-gluc opyranosyl as the auxiliary with the advantages of efficiency, simple operation and high yield. The plausible reaction mechanism was also brought up.3. After the detailedly studies on nucleophilic addition reaction of N-(2, 3, 4, 6-tetra-O-pivaloylated-D-glucopyranosyl)aldimine with TMSCN, we synthesized D-a-amino nitriles in the excellent yields highly stereoselectively for the successfully stereocontrolled formation of levetiracetam. This method is efficient, economical, safe and simple with high yield and high diastereomer ratio, avoiding the use of toxicreagents such as HCN and NaCN.4. The condensation reactions of the N-{2, 3, 4, 6-tetra-O-pivaloylated-D-glucopyra-nosyl)amine with a;/?-unsaturated aldehydes and the regio- and stereo- selectivity of the nucleophilic additions of trimethylcyanide to cr,y#-unsaturated aldimine have been studied. Based on the results of the experiments, it was proved that the optical glucopyranosyl group had played a significant role in the controlling of the regio- and stereoselectivity of the reaction. Therefore, a new method have been developed for the synthesis of /3, ^-Unsaturated a-amino acids which are of great useful for their biologically significant properties, such as antitumor, antibiotic and enzyme inhibitory.5. In order to synthesize the a-amino selenides with biologically significant prop -erties such as antivirus, antitumor and antioxidant, we carried out the nucleophilic addition of N-(2, 3, 4, 6-tetra-0-pivaloylated-D-glucopyranosyl)aldimine with trimethyl(phenyleno)silane and the hydrolysis of N-(2, 3, 4, 6-tetra-O-pivaloylat-ed-D-glucopyranosyl)-a-amino selenides. The initial research results showed that we had successfully synthesized the N-(2, 3, 4, 6-tetra-O-pivaloylated-D-glucopyranosy-l)-a-amino selenide, which would benefit the development of a new method for the stereoselective synthesis of optically active a -amino selenides.In addition to, the asymmetric syntheses, especially for the asymmetric syntheses using the carbohydrate as chiral auxiliary, are systematically reviewed in this dissertation.