Patent GB-1469384-A (GB)
Title: Tetracyclines
IPC: C07C237/26
Filed: 1975-06-20
Abstract: 1469384 Alkyl- and methylthioalkyl-tetracyclines SOC FARMACEUTICI ITALIA SpA 20 June 1975 [25 June 1974] 26270/75 Heading C2C A tetracycline of the general Formula I wherein R 1  represents a hydrogen atom, a hydroxy group or an acyloxy group having from 1 to 4 carbon atoms; R 2  represents a hydrogen atom or a methyl group; R 3  represents a hydrogen atom when R 2  represents a methyl group or otherwise represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a methylthioalkyl group having from 2 to 5 carbon atoms or a dimethylamino group; R 4  represents a hydrogen atom when R 3  represents a dimethylamino group or otherwise represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms or a methylthioalkyl group having from 2 to 5 carbon atoms; and R 5  represents a hydrogen atom, is reacted in the presence of a strong acid and in the absence of water with a sulphide of the general formula wherein R represents a hydrogen atom or an alkyl group having up to 3 carbon atoms, thereby to introduce according to the following stipulations one or more methylthioalkyl substituents of the formula(e) CH 3 -S-CHR- wherein R is as above defined: (a) if R 2 , R 3  and R 4  all represented hydrogen atoms, for one of R 3  and R 4 , both of R 3  and R 4  or all of R 3 , R 4  and R 5 , (b) if R 2  represented a methyl group and R 4  represented a hydrogen atom, for R 4  or both of R 4  and R 5 , (c) if R 2  represented a methyl group and R 4  did not represent a hydrogen atom, for R 5 , (d) if R 2  and R 3  both represented hydrogen atoms and R 4  did not represent a hydrogen atom, for R 3  or both of R 3  and R 5 , (e) if R 3  represented a dimethylamino group, for R 5 , (f) if R 3  represented neither a dimethylamino group nor a hydrogen atom and R 4  represented a hydrogen atom, for R 4  or both of R 4  and R 5 , (g) if R 3  represented neither a dimethylamino group nor a hydrogen atom and R<SP>4</SP> did not represent a hydrogen atom, for R 5 , and the methylthioalkyltetracycline derivative is either isolated or demethylthionated by refluxing in a solvent with Raney nickel to give the corresponding alkyltetracycline derivative (in which the or each alkyl substituent is of the formula RCH 2 -). Tetracycline derivatives of the general Formula I wherein R 1  represents a hydrogen atom, a hydroxy group or an acyloxy group having from 1 to 4 carbon atoms; R 2  represents a hydrogen atom or a methyl group; R 3  represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a methylthioalkyl group having from 2 to 5 carbon atoms or a dimethylamino group; and R 4  and R 5  each represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms or a methylthioalkyl group having from 2 to 5 carbon atoms: with the provisos that R 3  and R 4  do not simultaneously represent hydrogen atoms, that when R 2  represents a methyl group R 3  represents a hydrogen atom, that when R 3  represents a dimethylamino group R 4  represents a hydrogen atom and R 5  does not represent a hydrogen atom, and that when R 5  represents a hydrogen atom R 3  and R 4  do not represent (i) a hydrogen atom and a butyl group respectively, or (ii) a methyl group and a butyl group respectively, or (iii) a methyl group and a hydrogen atom respectively, are novel.