Napyradiomycin A2

Napyradiomycin SR ( 1), 16-dechloro-16-hydroxynapyradiomycin C2 ( 2), 18-hydroxynapyradiomycin A1 ( 3), 18-oxonapyradiomycin A1 ( 4), 16-oxonapyradiomycin A2 ( 5), 7-demethyl SF2415A3 ( 6), 7-demethyl A80915B ( 7), and ( R)-3-chloro-6-hydroxy-8-methoxy-alpha-lapachone ( 8) were isolated from the culture broth of Streptomyces antimycoticus NT17. These compounds are derivatives of the napyradiomycins isolated previously from Chainia rubra or Streptomyces aculeolatus. The structures of the new compounds, some of which exhibit antibacterial activities, were established by comparing their NMR data with data of related known compounds. The unique structure of 1, containing a highly strained ring, was established by NMR and was confirmed by X-ray analysis. Two of the compounds are C-16 stereoisomers of napyradiomycin A2 and are named napyradiomycins A2a ( 9a) and A2b ( 9b).

Napyradiomycins A2 and B4, new members of the napyradiomycins, have been isolated from the culture broth of Chainia rubra MG802-AF1. The structure of napyradiomycin A2 was elucidated as 16-hydroxy-17-methylenenapyradiomycin A1 by NMR studies. The absolute structure of napyradiomycin B4 was determined as 13-hydroxy-13-methylnapyradiomycin B1 by X-ray crystallography and therefore the configuration of C(4a) in other napyradiomycins is assumed as the R configuration. The geometrical isomerism of napyradiomycin C1 was estimated as 12E and 16E by nuclear Overhauser effect experiments.

Biosynthetic studies on napyradiomycins were carried out based on the incorporation of [2-13C]acetate and [1,2-13C]acetate. The alignment of acetate units suggested that the B and C rings of napyradiomycins are derived from a pentaketide, while ring A and the side chain may be synthesized from mevalonate.