By combination of chemical, XKand 13C NMR,and mass spectrometric studies, the structures of the three components of the antibiotic ramoplanin (A-16686), produced by Actinoplanes sp. ATCC 33076, have been elucidated. All the components have structures formed by a commondepsipeptide skeleton carrying a dimannosyl group and are differentiated by the presence of various acylamide moieties, derived from C8, C9 and C10 fatty acids. A-16686,n an antibiotic produced by Actinoplanes sp. ATCC33076,1} is active against aerobic and anaerobic Gram-positive bacteria, including methicillin-resistant Staphylococci and bacteria resistant to ampicillin and/or erythromycin.2~5) In particular, it is very active against a series of clinical isolates of strains of Propionibacterium acnes.® Preliminary physico-chemical characterization^indicated that A-16686 is formed by a peptidic core carrying two D-mannose units. Reversed-phase high pressure liquid chromatography (HPLC) showed at an early stage that it consists of three related factors, designated Al, A2 and A3, as shown in Fig. 1. Single fac-Factor F

1H and 13C NMR spectral studies of lipiarmycin in CDCI , and in pyridine-d; provided evidence for the six partial structures I-VI and the two sugar units 1 and 2. Acid methanolysis led to the isolation of methyl 2-O-methyl-4-O-homodichloroorsellinate-,3-rhamnoside, whose structure was determined by spectroscopic methods.Lipiarmycinl.2) is a chlorine containing antibiotic produced by Actinoplanes deccanensis ATCC 21983, active mainly against Gram-positive bacteria. While the weak in vivo activity delayed further developments, its mechanism of action has been the subject of many studies'-''.In a previous paper2) the preliminary characterization of lipiarmycin was reported, showing the presence of a sugar moiety and of many branched aliphatic chains. Furthermore, homodichloroorsellinic acid was isolated after acid hydrolysis. In this paper we report the structure elucidation of the sugar components and of the two compounds obtained by hydrolysis. In addition, the partial structures of some aliphatic moieties are deduced from 270 MHz 1H and 67.88 MHz 13C NMR spectroscopy.From elemental analysis and osmometric data, supported by 1H and 13C NMR spectroscopy, lipiarmycin has the molecular formula C52H72C1201e-1e• Spectroscopic Studies Fig. 1 shows the IR spectrum of lipiarmycin in CDC13. Absorption bands at 3600, 3560, 3540 and 3500 cm-1 are assigned by deuteration to OH functions, the last three of them being intramolecularly H-bonded. The spectrum shows three carbonyl absorptions at 1730 and 1690 cm-1, unchanged after deuteration, and at 1660 cm-I which shifts to 1640 cm-1 after deuteration.The band at 1690 cm'' is then assigned to a conjugated C=O and that at 1660 cm-1 to a C=O ester conjugated and H-bonded; the band at 1730 cm-1 is due to an aliphatic ester. In the double bond region a band at 1590 cm-1 (1580 cm-I after D,O addition) is associated with an aromatic moiety carrying one or more phenolic groups. These latter functions are confirmed by the presence of 6,0 bands at 1410 and 1220 cm-1 shifted by deuteration. Finally, the strong band at 1070 cm-1 (o _0) can be assigned to the anomeric group of a sugar. Table 1, where the various H-bearing groups are labelled with alphabetical letters. Examination of the 1H NMR data in CDCI, indicates that the total number of protons is 72 of which 5 are exchangeable. Furthermore, the exchangeable H at 5 11.5 is attributed to a phenolic OH

The kinetics and metabolic fate of 2'-14C-deflazacort, a new steroidal antiinflammatory agent, were studied in the cynomolgus monkey after both p.o. and i.v. administration (5 mg/kg). There is no unchanged deflazacort in the plasma or urine after either p.o. or i.v. treatment. As judged from the plasma AUC and urinary elimination values, the oral availability of both total 14C and metabolites seems to be lowered because of a route-dependent first-pass. Both radioactivity and the main metabolite (21-desacetyl deflazacort) are eliminated from the plasma with half-lives of 2--3-5 h. The i.v. administered 14C is eliminated mainly in the urine (52--55% of dose), but biliary excretion is also quantitatively important. Six metabolites were isolated from urine and identified by physico-chemical analysis. Among them desacetylated deflazacort and its 6 beta-hydroxy derivative were shown to be the major radioactive products in plasma and urine, respectively. Minor metabolites were: 21-desacetyl, 6 alpha-hydroxy deflazacort; 21-desacetyl, 5 alpha, 1-eno, deflazacort; 21-desacetyl, 20 beta hydroxy deflazacort; and 21-desacetyl, 11-keto deflazacort.

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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-