NMR spectroscopic analysis of new spiro‐piperidylrifamycins

Abstract

New spiro-piperidylrifamycin derivatives are presented. These compounds were synthesized from the reaction of 3-amino-4-iminorifamycin S and enantiomerically pure 4-piperidones, which generate diasteroisomeric rifabutin analogues with a new stereocentre at the spiranic carbon. The 1 H and 13 C NMR spectra of these new compounds, and also the configuration of the new stereogenic centres, were assigned using 2D NMR spectroscopic techniques. A preliminary study of the 1 H and 13 C NMR spectra of the starting compounds rifamycin S, 3-amino-4-iminorifamycin S and the related rifabutin was also carried out and as a result, their previously published 13 C NMR data were corrected.

MALDI‐TOF tandem mass spectrometric analysis of novel aza‐analogues of semi‐synthetic ansamycin antibiotic ‐ rifampicin

“…Many attempts at modification of the natural product rifamycin SV have been proposed and performed up to now, e.g. by introduction of alkylthio chain or alkylthio chain containing sugar moieties at C‐3 atom,7 removal of acetyl group at C‐25 atom from the ansa bridge,8 simultaneous introduction of amine group at C‐3 atom and imino group at C‐4 position or linkage of C‐3 and C‐4 positions by various substituted spiro9 or heterocyclic10 moieties. Because of some problems associated with the use of rifampicin in therapy against tuberculosis following from its toxicity,11 the interactions with the other drugs,12 resistance of some bacterial strains as well as taking into account important role of the substituent at C‐3 atom and the key role of hydroxyl groups for the presence of high antibacterial activity of Rif, we have synthesised series of its novel aza‐analogues (R1–R7—Scheme ).…”

Modifications, biological origin and antibacterial activity of naphthalenoid ansamycins

“…37,38 Furthermore, it was evidenced that for various rifamycins (including rifabutin, rifapentine, rifaximin, and rifampicin) the conformation of the ansa bridge and its arrangement relative to the central core are dependent on the phase (solid/liquid) or polarity and nature (protic/aprotic) of the solvent used. [39][40][41][42] The conformation exibility of the ansa chain for ansamycins, e.g. rifamycins, is not always concerned with atropisomerism, however, is crucial for chameleonic properties of this-type macrolactams, reected in a facile adaptation to the changing cell environment during Review Natural Product Reports transport of the drug to the target site.…”

Strong In Vitro Activities of Two New Rifabutin Analogs against Multidrug-Resistant Mycobacterium tuberculosis

“…Both of these compounds have the same stereochemical configuration at the spiranic carbon C-1Ј, which was determined to be R by 2D nuclear magnetic resonance (NMR), nuclear Overhauser effect spectroscopy (gNOESY), and rotational Overhauser effect spectroscopy (ROESY) experiments ( Fig. 1) (12). In the present study, we report in greater detail the in vitro antimycobacterial properties of RFA-1 and RFA-2 against a wide panel of RIF-susceptible and multidrug-resistant strains of M. tuberculosis and study the basis for their enhanced bioactivity by molecular dynamics calculations.…”