Presentation Type

Poster

Faculty Mentor’s Full Name

Nigel Priestley

Faculty Mentor’s Department

Chemistry

Abstract

Nonactin is a cyclic macrotetrolide antibiotic produced by Streptomyces griseus consisting of two monomers of (+)-nonactic acid and two monomers of (-)-nonactic acid. Following extraction and methanolysis of nonactin and its related nactins, e.g. monactin, methyl nonactate can be purified as a 70:30 mixture of the (-) and (+) enantiomers. Methyl nonactates contain four chiral centers, having a total of 16 stereoisomers. The (+) enantiomer has initially been shown to have a lower minimum inhibitory concentration (MIC) when tested against methicillin-resistant Staphylococcus aureus and other Gram-positive pathogens compared to its complimentary (-) enantiomer. The difference of activity between the enantiomers suggests chiral selectivity of the target. So far hundreds of antibiotic candidates have been synthesized from the core methyl nonactate structure, with three compounds; 31G11, 31G12, and 31E11, having high biological activity in non-optically pure mixtures. These compounds are being made optically pure for eight of the most synthetically accessible isomers. Determination of the optimal stereoisomer will be drawn from comparing the observed MIC values of each optically pure isomer when tested against several Gram-positive and Gram-negative bacteria.

Category

Physical Sciences

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Preparation of Enantiopure Methyl Nonactate Derivatives from Fermentation and its Use in Synthesis of New Antibiotics

Nonactin is a cyclic macrotetrolide antibiotic produced by Streptomyces griseus consisting of two monomers of (+)-nonactic acid and two monomers of (-)-nonactic acid. Following extraction and methanolysis of nonactin and its related nactins, e.g. monactin, methyl nonactate can be purified as a 70:30 mixture of the (-) and (+) enantiomers. Methyl nonactates contain four chiral centers, having a total of 16 stereoisomers. The (+) enantiomer has initially been shown to have a lower minimum inhibitory concentration (MIC) when tested against methicillin-resistant Staphylococcus aureus and other Gram-positive pathogens compared to its complimentary (-) enantiomer. The difference of activity between the enantiomers suggests chiral selectivity of the target. So far hundreds of antibiotic candidates have been synthesized from the core methyl nonactate structure, with three compounds; 31G11, 31G12, and 31E11, having high biological activity in non-optically pure mixtures. These compounds are being made optically pure for eight of the most synthetically accessible isomers. Determination of the optimal stereoisomer will be drawn from comparing the observed MIC values of each optically pure isomer when tested against several Gram-positive and Gram-negative bacteria.