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Synthesis and antimycobacterial activity of 2,1'-dihydropyridomycins.

ABSTRACT: Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of the potent antimycobacterial natural product pyridomycin (1), have been prepared from l-Thr, R- and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The 2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the enol ester moiety in the natural product is not critical for its biological activity. This finding establishes 2 as a potent and more practical lead for anti-TB drug discovery.

SUBMITTER: Horlacher OP

PROVIDER: S-EPMC4027526 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Synthesis and antimycobacterial activity of 2,1'-dihydropyridomycins.

Horlacher Oliver P OP Hartkoorn Ruben C RC Cole Stewart T ST Altmann Karl-Heinz KH

ACS medicinal chemistry letters 20121218 2

Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of the potent antimycobacterial natural product pyridomycin (1), have been prepared from l-Thr, R- and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The 2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the enol ester moiety in the natural product is not critical for its biological activity. This finding establishes 2 as a potent and more practical lead for anti-TB drug discovery. ...[more]

PMID: 24900646

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