Rifamycin Z, a novel ansamycin from a mutant of Nocardia mediterranea.

Abstract

Rifamycin Z is a novel ansamycin produced by a mutant of Nocardia mediterranea. Physico-chemical data indicate that it possesses a lactone-type structure directly derived from rifamycin W.During our studies on mutant strains of the rifamycin producer Nocardia mediterranea, we isolated a morphological variant which produced a mixture of novel ansamycins. We report the structure elucidation of the major component, rifamycin Z, together with its proposed biogenetic relationship with the ansamycins so far reported. Structure DeterminationEvidence for the structure of rifamycin Z (I) was obtained by comparing analytical and spectroscopic properties with those previously reported for rifamycin W1) (II). Elemental analyses and a molecular ion in a EI mass spectrum at m/z=651, as well as 1H and 13C NMR spectral data indicate I has a molecular formula C35H41NO11, i.e. I contains four hydrogens less than II (C35H45NO11). The UV-VIS spectrum of I in pH 7.38 buffer solution [;max, nm (s): 292 (21,700), 348 (10,800), 430 (sh), 550 (2,300)] is the same as that of II, indicating that the naphthoquinone chromophores in I and II are identical. This is confirmed by the mass spectrum of I, which shows a similar pattern of fragmentation of the chromophore as that of II, i.e. fragments at m/z=286, 274, 273, 258 and 246. The mass fragmentation attributable of the ansa chain indicated a loss of two molecules of water instead of four as in II2) , thus suggesting that the structural difference between I and II is in the ansa chain.One ionizable function with pKa 4.9 can be spectrophotometrically detected for I in aqueous solution. By potentiometric titration in methylcellosolve-H2O (4: 1), a pKa 6.1 is obtained. These observations indicate that the same acidic function exists on the chromophore of I as in II. Rifamycin Z is unstable in basic solution.The IR spectrum of I in CDC13 solution as compared with that ofII1, 3) has two additional bands [1730 (vc=o) and 1250 (vc-o-c) cm-1] assignable to a lactone group. Also, the different absorption of the OH groups in the ansa chain, in particular vOH-3600 cm-1, is related to a different hydrogen bonding, suggesting a different conformation of the ansa chain.The 1H NMR data of rifamycin Z (I) are reported in Table 1. When the data of I are compared with those of II1), it is evident that the former lack the AB system at d 3.78 and 4.08 ppm, due to CH2OH-34a and the paramagnetic shift at H-25. Since all the other protons show a similar data, the main structural variations must occur at C-34a and C-25. The different Jvlc values from H-23 to H-27 indicate that the conformation of the ansa chain in I is quite different from that in II, as may be expected from the lactonization of the COOH-34a with the OH-25. This difference in conformation is also reflected by the diamagnetic shift of nearly all the protons of I with respect to II; in fact, different aromatic solvent in-

Salinisporamycin, a novel metabolite from Salinispora arenicora

“…With the help of a detailed analysis, the naphthoquinone ring system of 1 had chemical shifts comparable to the literature values reported for rifamycin Z. 13 This result revealed that the 13 These results were supported from the assignment of 1 H-13 C connections made by HSQC correlations in solvent DMSO-d 6 . Consequently, these results showed the isomerization of the naphthoquinone ring system of 1 by different solvents.…”

“…13 [2M+Na] + , indicating the presence of the intermolecular exchange of 5 hydrogen atoms (data not shown). The UV spectrum of 1 was nearly identical with that of 3 in solvent MeOH.…”

Rifamycin W Analogues from Amycolatopsis mediterranei S699 Δrif-orf5 Strain

“…Based on the 1D and 2D NMR data, HRESIMS data and spectroscopic comparisons with those reported in the literature, compounds 8-13 were determined to be rifamycin Z (8) [28], 30-hydroxyrifamycin W-hemiacetal (9) [29], rifamycin W-hemiacetal (10) [25,30], 30-hydroxyrifamycin W (11) [30], rifamycin W (12) [25,27] and protorifamycin I (13) [31] (Figure S7).…”

Looking Back to Amycolatopsis: History of the Antibiotic Discovery and Future Prospects

“…Protorifamycin I No antibiotic activity [171,172] Rifamycin W Proansamycin X No activity against Gram-positive bacteria or Gram-negative bacteria [173] Rifamycin Z Rifamycin W No activity against Gram-positive bacteria or Gram-negative bacteria [174] 31-Homorifamycin W Rifamycin W No significant antibacterial, antifungal, or antiviral activity [81] Rifamycin SV Rifamycin W…”