title: 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.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zürich , 8093 Zurich, Switzerland.
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Horlacher
authors.affiliation: École Polytechnique Fédérale de Lausanne (EPFL), Global Health Institute , 1015 Lausanne, Switzerland.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Hartkoorn
authors.affiliation: École Polytechnique Fédérale de Lausanne (EPFL), Global Health Institute , 1015 Lausanne, Switzerland.
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zürich , 8093 Zurich, Switzerland.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Altmann
keywords: InhA; natural products; pyridomycin; total synthesis; tuberculosis