Patent GB-1243660-A (GB)
Title: Enduracidin derivatives
IPC: C07K1/00
Filed: 1968-11-22
Abstract: 1,243,660. Enduracidin derivatives. TAKEDA YAKUHIN KOGYO K.K. 22 Nov., 1968 [22 Nov., 1967: 22 Jan., 1968], No. 55538/68. Heading C2A. The invention concerns an enduracidin reduction product wherein two double bonds product wherein two double in enduracidin are saturated by hydrogen and are saturated by hydrogen the acid salts thereof. The enduracidin reduction product hydrochloride is characterized by hydrochloride is characterized the following properties:-decomposing at 234- 240 C.; having a specific rotation[α] D <SP>26</SP> of + 82.8 degrees (C=1À0, 70 per cent by volume methanol); Rf values obtained in paper partition chromatography are 0À450À1 with acetic acid : n-butanol : water (1:4: 5), 0.0 with n-butanol saturated with water, 0À800À1 1 with pyridine : n-butanol ; water (3:4:7); having U.V. absorption maxima, at #<SP>N/10</SP> max  HC1= 230 mÁ (#<SP>1%</SP> 1cm  = 201), 276 mÁ (#<SP>1%</SP>  1cm.  = 32.4), 282 mÁ (#<SP>1%</SP> 1cm  = 30.9), #<SP>N/10</SP> max. NaOH =250 mÁ (#<SP>1%</SP> 1cm  = 289), 293 mÁ (#<SP>1%</SP> 1cm.  = 68); having absorption values in its I.R. spectrum observed by the KBr disc method at 3À05 (strong), 3À25 (shoulder), 3À38 (shoulder), 3À45 (strong), 5.75 (shoulder), 5À95 (shoulder), 6À09 (strong), 6À23 (shoulder), 6À47 (shoulder), 6À55 (shoulder), 6À61 (strong), 6À95 (shoulder), 7À25 (middle), 8À16 (broad, strong), 8À51 (middle), 9À89 (middle), 10À40 (weak), 11À93 (middle) and 12À30 (weak) microns; slightly soluble in water; soluble in aqueous methanol, aqueous acetone, aqueous acetic acid, dimethylformamide, pyridine and dioxane; insoluble in acetone, ethyl acetate, ether and chloroform; giving positive reactions with ninhydrin, Barton's and Dragendorff reagents and discoloration occurs with alkaline potassium permanganate; elementary analysis of C=51À3 1À0%, H= 6À2#0À3%, N= 14À200À5% and Cl=4À500À3%; LD 50  value in mice of 350 mg./kg. (intravenous injection and Ig/kg. (intraperitoneal injection); having antimicrobial activity against gram-positive bacteria and phyto-oathosenic bacteria and no cross-resistance with tetracycline, chloramphenicol, erythromycin, cephaloridine, oleandomycin, kanamycin, streptomycin, penicillin-G, aminobenzyl-penicillin and neomycin. The endurac din reduction product is prepared by subjecting onduracidin or its salt to catalytic reduction in the presence of a metal catalyst at atmospheric or elevated pressure up to 20 kg./cm.<SP>2</SP>. Salts may be formed with inorganic (e.g. HC1) and organic (e.g. acetic) acids. A salt may be formed with an acid of formula X-(CH 2 ) n -SO 3 M wherein n is 1, 2 or 3, M is hydrogen or an alkali metal, and X is hydroxyl, amino or-SC 3 M, by reaction with the enduracidin reduction product. The invention also relates to compounds of formula:- En(NH 2 )r(NH m X (CH 2 )n-S0 3 M)p wherein En is the enduracidin or enduracidin reduction product residue, r is 0, 1 or 2, p is 1, 2 or 3 and r+p is 3, X is hydroxyl, amino or - SO 3 M, wherein M is hydrogen or an alkali metal, n is 1, 2 or 3, m is 1 or 2 and I is 0 or 1, and when n is 1, m is 1, I is 0 and X is hydroxyl, whilst, when n is 2 or 3, m is 2 and I is 1. Pharmaceutical compositions comprise at least one enduracidin reduction product or a salt thereof and a carrier. The antibiotic compositions may be administered orally, parenterally, topically or externally in the form of powders, capsules, syrups, oils, injections, ointments and tablets containing conventional excipients.