GB584062A - Manufacture of saccharide derivatives - Google Patents

Abstract

Saccharide derivatives of alicyclic and aliphatic alcohols are prepared by the interaction of the alcohol with an acylhalogenose characterised in that the reaction takes place in solution in the presence of an agent capable of binding hydrogen halides and that the volatile products of reaction are continuously removed by azeotropic distillation. The preferred agents capable of binding hydrogen halide are silver carbonate or silver oxide. Alicyclic and aliphatic alcohols mentioned as suitable starting materials for the present invention include testosterone, androsterone, corticosterone, dehydrocorticosterone, desoxycorticosterone, oestradiol or its mono-derivatives, genins of synthetic or natural cardio-active substances, and aliphatic or alicyclic alcohols such as butyl alcohol, menthol and borneol. Solvents which may be used include methylene chloride, tetrachloroethylene, chloroform, benzene, toluene, ethyl acetate and isopropyl ether. The preferred method of conducting the reaction is to add one or both of the reaction components to a mixture containing a condensing agent at a rate corresponding with the progress of the reaction. In examples: (1) Acetobromo-a -glucose in benzene solution is added slowly to a boiling benzene solution of transandrosterone containing silver carbonate. During the addition, the benzene is slowly distilled to give on working up the b -a -glucoside tetracetate of trans-androsterone. The mother liquors are treated with sodium methylate and worked up to yield trans-androsterone-b -a -glucoside. (2) A benzene solution of testosterone is reacted with acetobromo-a -glucose as in example (1) and the product worked up as before to give the b -a -glucoside tetracetate of testosterone. The mother liquors are similarly treated to give the glucoside which is reacetylated. (3) Cholesterol is reacted with acetobromo-a -glucose as in example (1) to form the glucoside tetracetate which is then saponified to cholesterol b -a -glucoside. An increased yield may be obtained by working under pressure with xylene as the solvent. (4) Desoxycorticosterone is reacted with acetobromo-a -glucose as in example (1) except that chloroform is used as the solvent. The b -a -glucoside tetracetate of desoxycorticosterone is formed, which on saponification with barium methylate yields the free glucoside. This, if desired, may be re-acetylated by acetic anhydride in pyridine. An increased yield is obtained by the use of benzene as a solvent. (5) Desoxycorticosterone is reacted with bromomaltose under the conditions of example (4) to give desoxycorticosterone - maltoside hept - acetate, which on hydrolysis with barium methylate gives the b -maltoxide of desoxycorticosterone. (6) Cis-borneol is treated with acetobromo-a -glucose under the conditions described in example (1) to form the tetracetyl glucoside of cis-borneol. (7) Oestradiol-3-monobenzoate is reacted with acetobromo-maltose under the conditions described in example (5) to form the b -maltoside heptacetate of oestradiol-3-monobenzoate. This on saponification with a N-solution of barium methylate in methanol forms the 17-b -maltoside of oestradiol. (8) acetobromo-a -glucose is reacted as described in example (5) with D 5:6, 20:22-3 : 21-dioxynorcholadienic acid lactone and saponified with barium methylate to form the free maltoside of D 5:6, 20:22 - 3 : 21 - dioxy - norcholadienic acid lactone, which may be re-acetylated to form the maltoside heptacetate. (10) Testosterone is reacted as in example (5) with acetobromomaltose, and the product saponified with barium methylate. The free testosterone maltoside is re-acetylated to form the b -maltiside heptacetate of testosterone.