GB878907A - Isonovobiocin and the conversion of isonovobiocin to novobiocin - Google Patents

Abstract

The invention relates to isonovobiocin which is an isomer of novobiocin in which the carbamyl group is in the 3-position instead of the 4-position. Novobiocin has the formula <FORM:0878907/IV (b)/1> Isonovobiocin is present in crude novobiocin and is biologically inactive. An aqueous solution of isonovobiocin at pH 9.5 to 11 on standing forms an equilibrium mixture containing two parts of novobiocin to one part of isonovobiocin. Crude novobiocin is therefore purified by treatment with aqueous acetone of 55 to 80, and especially 60% by volume in order to remove isonovobiocin preferentially to novobiocin, the resulting extract containing a mixture of novobiocin and isonovobiocian in a ratio of less than 1 e.g. two or more parts of isonovobiocin per part of novobiocin. An aqueous solution of a water-soluble alkali such as sodium carbonate, sodium hydroxide, potassium hydroxide and potassium carbonate is added to (a) the aqueous extract or (b) the solids obtained from the extract to produce a pH of 9.5 to 11.0 and the solution is allowed to stand at 15 to 35 DEG C. until the equilibrium mixture is obtained. The solution is acidified to pH 1.5, acetone added, and novobiocin crystallised therefrom. Isonovobiocin may be obtained pure by the countercurrent distribution of crude isonovobiocin in the solvent pair obtained by combining water, acetone, methyl ethyl ketone and n-hexane in the proportions 3 : 9 : 2 : 6 parts by volume. Treated with methanolic hydrochloric acid isonovobiocin is degraded to 2-O-carbamyl-4-O- methyl-5,5- dimethyl-L- lyxose which is not oxidised by periodic acid. Specification 832,140 is referred to.