Estudos metodológicos visando a síntese da biotina a partir da hidantoína

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Biotin (1), a member of the vitamin B complex group, has been an attractive synthetic target due to its biological activity and its applications in different fields such as immunology, radiotherapy and bioanalytical chemistry. In this thesis we report some experimental results for an alternative biotin synthesis, using hydantoin (146) as starting material. The N-benzylated and N,N-dibenzylated compounds, 147a and 147b, as well as the derivatives 147c, 147d and 147e were obtained by alkylation and acylation, respectively, from hydantoin. The intermediates 147a-147e were submitted to crossed aldol condensations with methyl 6-oxo-hexanoate (148), mediated by 1M of tert butoxide of potassium. These reactions occurred only with the compounds 147c-e which were converted into the Z isomer 149a. The reactivity and influence of the protective groups of 147a-e and of respective enolate ions 147a-f were studied by DFT quantum method, which showed to be a useful tool for predicting the experimental behavior of such compounds undergoing an aldol condensation. The 1,4-addition of methyl thioglycolate (166) to the compounds 150a and 150d (protected with Boc) were accomplished with triethylamine and the chiral base cinchonine. For the derivative 150a, the conjugated addition with both bases produced an isomeric mixture of 151a. Similar result for 150d was obtained using triethylamine under same experimental conditions. However, the conjugated reaction with this derivative, promoted by the alkaloid cinchonine, probably formed the SS diastereomer 151d, confirmed by spectroscopic data 1 ( H NMR). However, the cyclization step for 151a and 151d did not to lead to the desired tetrahydrothiophenic ring of biotin (1).

ASSUNTO(S)

síntese hidantoína quimica organica biotina

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