Structure and biological activity of lipiarmycin B.

Abstract

Actinoplanes deccanensis ATCC21983, the producer of antibiotics lipiarmycin A3 and A4, furnished also a related antibiotic designated lipiarmycin B, active against Gram-positive bacteria, including anaerobes, and against Neisseria. The structures of the two major components, B3 and B4, were elucidated from their physico-chemical properties, XHand 13C NMR spectra and fast atom bombardment mass spectra data in comparison with lipiarmycins A3andA4.Fermentation of Actinoplanes strain ATCC21983 produced the antibiotic lipiarmycin1»2), later called lipiarmycin A, which is a complex of two minor factors and two major factors A3 and A4. The structures of lipiarmycins A3 and A4 have been elucidated by chemical degradation and NMR studies3~5) ( Fig. 1) and presented at the 14th IUPAC Symposium on the Chemistry of Natural Products (Poznan, 1984)4).Pilot plant fermentations furnished a crude material which by chromatographic techniques was shownto contain an additional factor designated lipiarmycin B. This report describes the isolation, physico-chemical properties and biological activity of lipiarmycin B. The structures of the two major components of lipiarmycins B, B3 and B4, were elucidated by chemical and NMRstudies in comparison with lipiarmycins A3 and A4.Isolation of Lipiarmycin B The fermentation of Actinoplanes deccanensis ATCC21983 and the recovery were carried out as previously described0. Twomain spots attributable to biologically active substances were revealed in the crude materials by TLCunder the conditions described in Table 1. The spot with the higher Rf (which under these conditions appears homogeneous) corresponds to lipiarmycin A and the other to lipiarmycin B.Pure lipiarmycin B was obtained by silica gel chromatography under pressure followed by a purification step at atmospheric pressure.Lipiarmycins B3 and B4 Silanized silica gel TLC and reversed phase HPLCrevealed that lipiarmycin B is composed of two minor and two major factors. The latter have been designated lipiarmycins B3 and B4. Suitable quantities were prepared by preparative HPLCor by flash chromatography.Physico-chemical Properties of Lipiarmycin B Some physico-chemical properties are shown in Table 1 in comparison with those of lipiarmycin

Fidaxomicin Is an Inhibitor of the Initiation of Bacterial RNA Synthesis

“…Because of the similarity in FDX structure to the structures of LPR [1, 2], it was expected that they would share the same target. We found that FDX inhibited both RNAP isolated from C. difficile by the method of Pich and Bahl [12] and RNAP from Escherichia coli in a radiolabeled uridine triphosphate incorporation assay [13].…”

“…FDX is structurally similar to compounds in lipiarmycin (LPR), a fermentation mixture [1, 2], which has been shown to inhibit a variety of bacterial RNA polymerases (RNAPs) [3–7]. …”

Natural Products as Platforms To Overcome Antibiotic Resistance

“…268 Furthermore, lipiarmycin was identified as an inhibitor of RNA synthesis. 269 Sometime later, the structure was elucidated, and lipiarmycin ( 350 ) was shown to consist of a highly unsaturated 18-membered macrolactone bearing acylated rhamnose and noviose sugars, 270 and the later discovered tiacumicin B was shown to have the same structure (Figure 36). 271 …”

A comprehensive review of glycosylated bacterial natural products

“…There are only 23 reported bacterial 18-membered glycosylated macrolides the majority of which are tiacumycins and lipiarmycins 746,747 from Micromonospora , Dactylosporangium , Actinoplanes and Catellatospora . All analogs share a common macrolactone ring O -glycosylated at C-11 with variants of the branched 5′- C -methyl-β-L-rhamnose ( 193a–f ) or at C-20 with variants of β-L-rhamnose ( 322a ) (Fig.…”