Structural characterization by NMR of rifabutinol, a derivative of rifabutin.

Rifabutin, a naphthalenic ansamycin, is a specific inhibitor of bacterial DNA-directed RNA polymerase and inhibits in vitro the replication of HIV-1. The synthesis of rifabutinol by PtO2–NaBH4 reduction of rifabutin in ethanol is described. Full assignments in CDCl3 are presented of the 1H and 13C NMR resonance signals using two-dimensional homonuclear and heteronuclear correlation techniques and selective proton decoupling methods. The three-dimensional structure of the ansa-chain of rifabutinol was calculated from NOE contacts and vicinal coupling constants, using a simulated annealing protocol starting from random coordinates. Measurements of the 13C T1 relaxation times of rifabutin in solution are consistent with a rigid ansa-chain. Copyright © 2000 John Wiley & Sons, Ltd.