Patent GB-924472-A (GB)
Title: Antibiotics prepared from rifamycin b
Inventor: TIMBAL MARIA TERESA
IPC: C07D498/08
Filed: 1959-08-07
Abstract: <PICT:0924472/IV(a)/1> <PICT:0924472/IV(a)/2> <PICT:0924472/IV(a)/3> <PICT:0924472/IV(a)/4> The invention relates to the antibiotics Rifamycin S having the following properties:-formula C37H45-49NO12; C=63.25%, H=7.03%, N=2.07%, O=27.23%, OCH3= 4.62% and COCH3=6.19%; melting point 180 DEG -182 DEG C.; [a ]20D=+476 DEG  (C=0.1, methanol); insoluble in water and dilute mineral acids, slowly dissolving in alkali metal hydroxides with red-violet colouration; fairly soluble in methanol, ethanol, acetone and ethyl acetate, less soluble in diethyl ether and very slightly soluble in petroleum ether; positive Tollen's, Fehling and ferric chloride reactions; U.V. maxima at 279 mm , 340mm  and 401 mm  is 0.1N.HCl and at 317 mm  and 325 mm  in phosphate buffer pH.7.3; Pka=7.1 and existing in two forms having I.R. spectra as shown in Figs. 2 and 7, Rifamycin O having the properties:-formula C39H47-51NO14; C=62.53%, H= 6.46%, N=1.74%, O=29.37%, OCH3= 4.23% and COCH3=5.59%; decomposing at 160 DEG C.; [a ]20D = +71.5 DEG  (C=1.dioxane); practically insoluble in water and dilute mineral acids, slowly soluble in alkali metal hydroxides with intense red-violet colouration, slightly soluble in methanol, ethanol, and ethyl acetate and fairly soluble in acetone; positive Tollen's, Fehling and ferric chloride reactions; U.V. maxima at 226mm , 273mu and 370 mm  in methanol; Pk1 = 7.7 and Pk2 = 10.75; and having an I.R. spectrum as shown in Fig. 4 and Rifamycin S.V. having the properties:-formula C37H47-51 NO12; C=62.85%, H=7.15%, N=2.08%, OCH3=4.4% and COCH3=6.15%; decomposing at 140 DEG C.; [a ]20D = -4 DEG  (C1.5 in dioxane); Pk 1/2 =2.7; soluble in alkali metal bicarbonates, very slightly soluble in dilute mineral acids, very soluble in methanol, ethanol, acetone and ethyl acetate, soluble in diethyl ether and slightly soluble in petroleum ether; positive Tollen's, Fehling and ferric chloride reactions; U.V maxima at 313 mm and 445 mm  in phosphate buffer pH=7.3 and having an I.R spectrum as shown in Fig. 6.  Rifamycin S is prepared by (a) allowing an aqueous solution of Rifamycin B (see Specification 877,732) or one of its alkali metal salts to stand for 15-20 days or (b) by oxidising Rifamycin B with an oxidising agent of the peroxy type such as hydrogen peroxide or sodium persulphate, nitrous acid, ceric chloride or auric chloride in a solvent which is an aqueous aliphatic alcohol of 1-8 carbon atoms, which may be admixed with acetone, under strong acid conditions pH 1 or less.  The Rifamycin S is isolated by extracting, when necessary after acidification, with an alkyl acetate containing 1 to 8 carbon atoms in the alkyl group, evaporating the extract and precipitating with petroleum ether and purifying by counter current extraction.  If the pH of reaction (b) above is 6-8 and acetone is omitted from the solvent Rifamycin O is formed which under the action of mineral acids forms Rifamycin S.  On mild reduction with ascorbic acid, isoascorbic acid or dihydroxyacetone Rifamycin S forms Rifamycin SV in a solvent such as an aqueous solution of an aliphatic alcohol containing 1 to 8 carbon atoms.  If sodium ascorbate is used the sodium salt of Rifamycin SV is formed. The Rifamycin S.V is isolated by extraction of the solvent with a water-immiscible solvent such as benzene, alkyl acetate or a water-immiscible aliphatic alcohol.  On treatment of the Rifamycin S, O and SV with acetic anhydride in pyridines, Rifamycin O and S form their mono acetyl derivatives and Rifamycin SV forms its triacetyl derivative.  Rifamycin SV forms salts with alkali and alkaline earth metals, dibenzylamine, dibenzylethylenediamine, quinine, 2-methylaminoheptane, 1-pchlorobenzyl- 2-pyrrolidylmethylbenzoimidazole, piperidine, piperazine and procaine.