Synthesis Of Some Rare Heptose And Glycosylated Derivatives From Cheap Monosaccharides

Synthesis and modification of carbohydrates with biological activity from monosaccharides which are abundant in source is one of important fields for the carbohydrate chemistry research. This paper, focusing on atom economic and environment-friendly development requirements of modern synthetic chemistry, was primarily concerned with the current synthesis and the methodological research of rare heptulose and glycosides in view of existing situation that some carbohydreate drugs or their precursors could not serve the needs of biochemical, pharmacological and clinical researches.First of all, three methods were studied in the synthesis of nature rare heptulose.(1) Synthesis of D-glucoheptulose was realized by molybdic acid as catalyst, with the yield of 37% in 4 steps that successively were hydroxymethylation on C-2 of 2,3;5,6-di-O-isopropylidene-D-mannfuranose, acquiring 2-C-hydroxymethyl-D-mannose after deprotection of isopropyaltion, and then preparation of the target product through hydroxymethyl transferred from C-2 to C-1 and simultaneity aldose changed to ketose by molybdic acid-catalyzed carbon-skeleton rearrangement.(2) D-mannoheptulose was synthesized with the yield 39% in 4 steps (purity>99%) that were obtaining mannoheptu-glycal through elongation of carbon chain of 2,3,4,5,6-pent-O-benzyl-D-mannose via Wittig reaction, getting the intermediate of a-hydroxy semi-ketal structure by selective oxidation to olefinic bond using KMnO4/HOAc system as the key step, and preparing the target molecular via deprotection of benzyls, hydrolysis under acid condition.(3) Preparation of benzylation derivatives of D-glucoheptulose, D-mannoheptulose, D-galactoheptulose was carried out with the yield 35% in 2 steps that were iodomethylated addition to ester carbonyl of sugar acid lactone using CH2I2/n-BuLi system, and hydrolysis under base condition.Three methods introduced above, having the advantages of mild condition and the reagents with easy availability, enrich and develop methodological research of synthesis of rare heptulose, which has major theoretic value and application prospect.Secondly, preliminary synthesis and methodological research of benzylation derivatives of Valielone (the yield 95%), Validone (the yield 20%) and analogues of Valiolone (the yiled of 4 steps was 36%), Valielone (the yield 90%) with D-mannose configuration were processed on the basis of successful synthesis of tert-O-benzyl-Valiolone done by our research team, which provided experimental basis for the precursors of these glycosidase inhibitor drugs.Finally, there were two aspects of the synthesis of glycosides with biological activity.(1) Stereospecific glycosylated modifications of paeonol-a kind of traditional Chinese medicine, and 2,4-dihydroxyphenyl ethanone that was metabolized intermediate of paeonol in organism, were actualized from tert-O-acetyl-a-glucopyranosyl/galactopyranosyl bromide as glycosyl donors with the yield of the glycosylated step 30-73%, and all the products were P-glycosides completely.(2) A novel series of 1'-iodopropargyl glycosides were synthesized through only two steps including glycosylated reaction with propargyl alcohol (the yield 50-90%), iodo-substitution (the yield 75-92%) from seven common monosaccharides without protection. Four kinds of synthetic 1'-iodopropargyl glycosides, which were chosen to carry out antibacterial test, had inhibitory activity to some normal kinds of fungi arousing diseases of crops, which offered a new opinion for the research of environmental protective pesticide with low toxicity.