Stereochemistry of enacyloxins. Part 3. (12′S,17′R,18′S,19′R)-Absolute configuration of enacyloxins, a series of antibiotics from Frateuria sp. W-315

Abstract

The absolute configuration of the 12′,17′,18′,19′-positions of enacyloxins (ENXs), a series of polyhydroxy-polyenic antibiotics from Frateuria sp. W-315, was determined. As degradation of decarbamoyl (dec) ENX IIa gave (5R,6S,1′E)-6-(but-1′-enyl)-5-chloro-5,6-dihydro-2H-pyran-2-one, which corresponded to the 15′–23′ skeleton of dec ENX IIa, its enantiomers were synthesized from tri-O-acetyl-D-glucal. Comparison of the HPLC retention time of these naturally derived and synthetic compounds revealed the 17′R,18′S,19′R-configuration of ENXs. Hydrogenation and oxidation of ENX IIa gave methyl 13-hydroxy-6,12-dimethyltridecanoate, which was converted to the 13-MTPA ester. Comparison of the ¹H NMR chemical shifts and the coupling constants with the model compounds revealed the 12′S-configuration. This absolute stereochemistry is necessarily applicable to other enacyloxins.