Antibiotic a 42867 derivative

Antibiotic A 42867 pseudoaglycon and the pharmaceutically acceptable salts thereof having the following physico-chemical parameters (unsalified form):

• (A) ultraviolet absorption which exhibits the following absorption maxima:
• ______________________________________ Lambda max (nm) ______________________________________ (a) 0.1 N HCl 279 (b) Water 279 305 (shoulder) (c) phosphate buffer pH 7.4 279 (e) 0.1 N KOH 299 265 (shoulder) ______________________________________
• (B) infrared absorption spectrum in nujol mull which exhibits the following absorption maxima (cm-.sup.-1):
• 3700-3100, 3000-2800 (nujol);
• 1650;
• 1590;
• (nujol);
• 1375 (nujol);
• 1305;
• 1240;
• 1210;
• 1160;
• 1130;
• 1060;
• 1010;
• 950;
• 870;
• 835;
• 720 (nujol)
• (C) .sup.l H-NMR spectrum which exhibits the following groups of signals (in ppm) at 250 MHz (Bruker Instruments) recorded in DMSO d.sub.6 (hexadeuterodimethylsulfoxide) using TMS as the internal standard (0.00 ppm), (delta=ppm):
• Sugar moiety:
• 1. 22,d [CH.sub.3 --(CH)];
• 1.50,s [CH.sub.3 --C(NH.sub.2)];
• 2.25, m [CH.sub.2 --(CH)];
• 3.60, m [CH--(CH.sub.3)];
• 4.90, d (anomeric proton)
• Core moiety:
• ##STR8##
• 2. 32, s [CH.sub.3 --(NH];
• 2.49, s (solvent DMSOd.sub.5);
• 3.35, br [H.sub.2 O];
• 4.23-6.35 [aromatic and peptidic CH's];
• 6.35-9.50 [aromatic CH's, peptidic NH's and phenolic OH's]
• s=singlet;
• d=doublet;
• m=multiplet;
• br=broad
• (D) retention time (R.sub.t) of 2.88 relative to antibiotic A 42867 (R.sub.t =8.45 min) when analyzed by reverse phase HPLC under the following conditions:
• column:
• Ultrasphere ODS (5 micrometer) Altex (Beckman) 4.6 mm (i.d.).times.250 mm
• pre-column:
• 3 cm Brownlee Labs RP 18 (5 micrometer)
• eluents:
• (A) (2.5 gr/l) NaH.sub.2 PO.sub.4 /CH.sub.3 CN, 98:2 (v/v) adjusted to pH 6.0
• (B) (2.5 gr/l) NaH.sub.2 PO.sub.4 /CH.sub.3 CN, 30:70 (v/v) adjusted to pH 6.0
• Elution mode:
• linear gradient from 5% to 60% of B in A in 40 min
• flow rate:
• 1.8 ml/min
• U.V. detector:
• 254 nm
• internal standard:
• antibiotic A 42867 (R.sub.t =8.45 min)
• (E) elemental analysis showing the presence of one chlorine atom per molecule
• (F) 2D .sup.1 H-NMR NOESYPH analysis showing that the molecular chlorine atom is on ring 2 and not on ring 6, on the basis of Nuclear Overhauser effect (dipolar coupling through space) and scalar coupling through chemical bond, in fact:
• (a) on the basis of scalar coupling, proton 2b (see formula I) shows only a meta coupling with 2f but no ortho coupling;
• (proton 2b is on ring 2 and not on ring 6 on the basis of the following dipolar coupling:
• 2b .fwdarw.Z'2;
• 2b .fwdarw.(Z2)OH;
• (Z2)OH .fwdarw.Z'2;
• Z'2.fwdarw.X2)
• (b) on the basis of scalar coupling, proton 6b (see formula I) shows an ortho coupling with proton 6c (dipolar coupling 6b.fwdarw.6c;
• Z6-6b;
• Z6.fwdarw.X6)
• (G) a fast atom bombardament (FAB) mass spectrum with M+H.sup.+ at about 1251 (the theoretical cluster ion peaks for the formula C.sub.60 H.sub.64 N.sub.9 O.sub.19 Cl+H range from 1250 to 1255, average value 1251.68). The FAB spectrum was obtained with a VG 70-250 instrument, bombarding gas Xenon;
• beam energy 8 KV;
• accelerating voltage 6kV;
• matrix thioglycerol-glycerol, 2:.
• (H) acid and basic functions capable of forming salts.