Estudo quimioenzimatico da sintese de um analogo do residuo N-terminal de nikkomicinas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

Nikkomycins belong to a group of nucleoside peptides antibiotics produced by streptomycets. These compounds are potent chitin synthetase inhibitors and they exhibit fungicidal, insecticidal, and acaricidal activities. Our approach began with an asymmetric reduction of ethyl benzoylacetate 37. We evaluate the biocatalytic potential of some brazilian microorganisms of Tropical Cultures Collection (CCT)of Tropical Research Foundation "André Tosello": Rhodotorula minuta CCT 1751, Rhodotorula glutinis CCT 2182, Pichia kluyeri CCT 3365, Pichia stipitis CCT 2617 and Candida utilis CCT 3469, besides the yeast Saccharomyces cerevisiae commercially available. The optimum result was found with Pichia kluyeri immobilized in calcium alginate and pH 4,5 (ee >95%, 85% yield). The next step involved the protection of the OH-function as its TBS ether followed by ester saponification to afford the corresponding carboxylic acid ethyl 3-[t-butyldimethylsilyl]oxy-3-phenylpropanoic acid 36 (80% yield). Treatment of 36 with EDCI and DMAP followed by ozonolysis afforded the required 2-oxo ester methyl 4-[t-buthyldimethylsilyl]oxi-2-oxo-4-phenylbutanoate 35 with maintenance of stereochemical integrity of the molecule. The introduction of methylene group has been done via direct Mannich a-methylenation with morpholine and p-formaldehyde to afford methyl 4-[t-buthyldimethylsilyl]oxi-2-oxo-3-methylene-4-phenylbutanoate 34. Finally, the second and third stereogenic centers were created by reduction of both groups methylene and ketone via catalytic hydrogenation using Pd/C as catalyst to afford only methyl 4-[t-buthyldimethylsilyl]oxi-2-hydroxi-3-methyl-4-phenylbutanoate 47.

ASSUNTO(S)

redução (quimica) biomoleculas drogas - analise reações quimicas

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