Studies On The Synthesis Of β-Hydroxy α-Amino Acids And Their Applications In The Synthesis Of Natural And Pharmaceutical Molecules

The thesis aims at the studies on the synthesis ofβ-Hydroxy-α-Amino acids and their applications in the synthesis of natural and pharmaceutical moleculesPartⅠDiastereo-and enantioselective synthesis ofβ-Hydroxy-α-Amino acidsβ-Hydroxy-α-amino acids are important constituents of peptides and related compounds as well as other complex natural products. Additionally, they may serve as useful precursors and chiral auxiliaries in organic synthesis. As a consequence of the essential role played byβ-hydroxy-α-amino acids in biological systems and their utilities as synthetic building blocks, a number of useful strategies utilizing chemical and enzymatic methods have been devised for their preparations. Our group has developed an aldol reaction between aldehydes and the enolates of tricyclic iminolactones 1a and 1b, which are derived from natural (1R)-(+) camphor as chiral glycine templates to generate optically pureβ-hydroxy-α-amino acids in good yield and high diastereoselectivity (up to dr:>25:1)PartⅡAsymmetric synthesis of natural product (+)-lactacystin(+)-Lactacystin is a potent and selective 20S proteasome inhibitor isolated from the culture broth of Streptomyses sp. OM-6519 by Omura et al in 1990. Its interesting structure contains hydroxyls at bothβ-positions of theα-amino acid. So we use our methodology of synthesis ofβ-Hydroxy-α-amino acids to the lactacystin synthesis. Fortunately, we successfully synthesized the key intermediate oxazolidine 15 for lactacystin synthesis, moreover, the rest 3 isomers of oxazolidine can also be synthesised conviniently. So we anticipated to synthesize the diastereoisomers of (+)-lactacystin to investigate the structure activity relationship.Part III Asymmetric synthesis of pharmaceutical molecular chloramphenicol, thiamphenicol and bioactive molecule sphingasineChiral amino alcohols are important components of natural and pharmaceutical molecules. Broad-spectrum antibiotics chloramphenicol and thiamphenicol are active against both gram-poasitive and gram-negative microorganisms. Chloramphenicol, thiamphenicol and sphingasine are allβ-Hydroxy-α-amino alcohol. So we can also successfully use our methodology of synthesis ofβ-Hydroxy-α-amino acids to synthesis these pharmaceutical molecules.