Synthesis of AminoaÃÃcares and Compostos GlicoheterocÃclicos / SÃntese de AminoaÃÃcares e Compostos GlicoheterocÃclicos

AUTOR(ES)
DATA DE PUBLICAÇÃO

1997

RESUMO

In the present work, the synthesis of new 2,3-unsaturaed glycosides, amino and branchedchain amino sugars is reported. Reaction of tri-O-acetyl-D-glucal (20) with five alcohols 72a-e using Ferrierâs method provided 2,3-unsaturatd glycosides 73a-e. Deacetylation of compounds 73a-e followed by allylic oxidation furnished enones 75a-e, which are important precursors for amino and other sugars. Addition of diazomethane to C(2)-C(3) double bond of 75d,f provided compounds 104d,f. Reduction of the latter compounds with sodium borohydride or hydrogenation with platinum (IV) oxide followed by acetylation yielded compounds 116d,f e 117d,f. It was not possible to break the N-N bond of the pyrazoline ring in 104d,f. The structures of these compounds were elucidated with the help of infrared and proton magnetic resonance spectroscopy. Addition of methylideneaniline Noxide to the C(2)-C(3) double bond in 75b,d,f occurred from the opposite site of the aglycone to give isoxazolidines 106b,d,f. Hydrogenation using platinum (IV) oxide as catalyst of these compounds individually caused the reduction of the keto function at carbon C(4) as well as the cleavage of N-O bond of the isoxazolidine ring and provided compounds 121b,d,f, which in turn were acetylated to give three new branched-chain amino sugars 122b,d,f in excellent yields. Addition of azide ion to enones 75d,f provided compound 112d,f which upon reduction with sodium borohydride, catalytic hydrogenation and acetylation furnished amino sugars 127d,f. Another series of compounds (R e S)-1-Methyl-3-[3-(aryl)-1,2,4-oxadiazol-5-yl] propyl 2,3-dideoxy-Ã-D-erythrohex- 2-enopyranoside 149a-e e 150a-e have been synthesized from 4-[3-aryl-1,2,4-oxadiazolâ5-yl]- 2-butanols 148a-e and tri-O-acetyl-D-glucal (20) again as a mixture of diastereomers. Deacetylation of these compounds yielded 151 e 152 which were separated by column chromatography to give pure products. The structure of one of the diastereoisomers 151d was determined by X-ray crystallography. Semi-empirical molecular orbital calculations (AM1) were also carried out for compounds 116d,f, 106b,d,f, 151a-e and 152a-e in order to get an idea about their stable conformations. Finally, glycosides 162, 163, 164, 165, 166, 167, 168 e 169, with phthalimidodomethyl group as an aglycone, have been synthesized from tri-O-acetyl-D-glucal (20) and N-hydroxymethylphthalimide (161). Some of these compounds, for example, 162, 165, 167, 168 and 169 have been tested for their hypolipidemic activity in mice, where significant reduction of plasma cholesterol and triglyceride levels have been observed.

ASSUNTO(S)

hipolipÃmicas activities triglicerÃdeos plasmÃticos plasmÃticos triglicerÃdeos atividades hipolipÃmicas engenharia de producao

ACESSO AO ARTIGO

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