Reação de arilação de Heck regio e estereosseletiva da 3-desidroprolina com sais de arildiazonio : aplicação na sintese total de analogos neuroexcitatorios do acido acromelico / Regio and stereoselective Heck arylation of 3-dehydroprolines with aryldiazonium salts. Total synthesis of the neuroexcitatory acromelic acid analogues

AUTOR(ES)

Kezia Peixoto da Silva

DATA DE PUBLICAÇÃO

2006

RESUMO

The Heck arylation of chiral 3-dehydroprolines using various aryldiazonium salt resulted in the formation of a series of 4-aryl-dehydroprolines of potential biological interest. The application of aryldiazonium salt in this arylation reaction offers several advantages over traditional Heck reactions such as mild reactions conditions of phosphine-free conditions and shorter reaction times. The 4-aryl-dehydroprolines were envisioned as potential precursors for the synthesis of a number of acromelic acid analogues, a potent neuroexcitatory neurotransmitter. The Heck arylation reaction of chiral 3-dehydroprolines was obtained in high yields under two basic protocols using acetonitrile-water or methanol as solvent; both methods use mild and phosphine-free conditions. A comparative study was designed involving the Heck arylation of 3-dehydroprolines using traditional electrophiles, such as aryltriflates and arylhalides. Among the traditional conditions tested (Jeffery, Crisp and Fu) only the conditions of Jeffery resulted in the formation of the Heck adduct, in rather low yields. The o-methoxyphenyl acromelic acid analogue, which displays high neuroexcitatory activity, was obtained from a Heck adduct by a sequence of reations involving Michael addition, selenylation and oxidative deselenylation. Next, catalytic hydrogenation, decarboxylation, and epimerization resulted in the desired protected analogue of the acromelic acid after 13 steps and with an overall yield of 8% from 4-trans-hydroxyproline. Comparison of the spectral data obtained for the compound synthesized herein and those published in the literature confirmed the structure of the acromelic acid analogue, including its absolute stereochemistry

ASSUNTO(S)

cainatos acromelic acid sais de diazonio heck reaction kainoids acido acromelico reação de heck diazonium salts

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