GB1312148A - Mutilin derivatives - Google Patents

Abstract

1312148 Mutilin derivatives BIOCHEMIE GmbH 10 July 1970 [25 July 1969] 33504/70 Heading C2A Novel mutilin derivatives having the Formula (I) wherein either (i) Y is vinyl, Z is hydrogen and X is -CO-COOH, -CO-CH 2 -R 1 in which R 1 is hydrogen, C 1 -C 4 alkyl, -S-(C 1 -C 5 ) alkyl, -S-(C 1 -C 5 ) alkyl substituted by one or more -NH 2 , -OH or -COOH groups, -S-benzyl, -S-phenyl, -S-phenyl substituted by -COOH or one or two -OH groups, -S-pyridyl, (N,N - tetramethylene - thiocarbamoyl)-mercapto, dithiocarbonic acid-O- (C 1 -C 5 ) alkyl, thiocyanato, azido, chloro, bromo or iodo; or (ii) Y is ethyl, Z is hydrogen and X is -CO-CH 2 -NH 2 or or (iii) Y is hydrogen, Z is acetyl and X is hydrogen, are prepared by (a) reacting the novel compound mutilin 14-tosyloxyacetate of Formula (II) with a compound MeR 1 in which Me is alkali metal and R 1 is as above to give a compound Ia wherein Y is vinyl, Z is hydrogen and X is -CO-CH 2 -R 1 in which R 1 is as above; (b) oxidizing pleuromutilin to give a compound Ib wherein Y is vinyl, Z is hydrogen and X is -CO-COOH; (c) reducing a compound (I) in which Y is vinyl, Z is hydrogen and X is -CO-CH 2 -R 1 where R 1 is bromo, iodo or thiocyanato to give a compound Ic wherein Y is vinyl, Z is hydrogen and X is -CO-CH 3 ; (d) hydrogenating a compound (I) in which Y is vinyl, Z is hydrogen and X is -CO-CH 2 -N 3 to give a compound Ie wherein Y is ethyl, Z is hydrogen and X is -CO-CH 2 -NH 2 ; (e) diazotizing the compound Ie to give a compound Ig in which Y is ethyl, Z is hydrogen and X is (f) selectively saponifying a compound (I) wherein Y is vinyl, Z is acetyl and X is -CO-CH 2 -OCOCH 3 to give a corresponding compound wherein X is hydrogen; and (g) selectively saponifying a compound (I) wherein Y is vinyl, and Z and X are each -CO-(C 1 -C 5 ) alkyl to give a corresponding compound wherein Z is hydrogen. Mutilin 14-tosyloxyacetate (II) is prepared by reacting pleuromutilin with p-toluene sulphochloride. Reaction (a) above is effected in an inert optionally aqueous solvent at 20-60‹ C., the alkali metal tosylate produced being filtered off. Reaction (b) is carried out with MnO 2 in a solvent in the presence of a base. Reaction (c) is effected in absolute ethanol with aluminium powder. The hydrogenation (d) is conducted with hydrogen in the presence of palladinized charcoal. The diazotization (e) is effected with NaNO 2 in acidic aqueous solution at about 0‹ C. The selective saponification (f) is carried out with mineral acid, and the saponification (g) with ethanolic sodium hydroxide.