GB749715A - A novel derivative of pantetheine and the manufacture and uses thereof - Google Patents

Abstract

The invention comprises S-benzyl pantetheine and its preparation by reacting a compound of the general formula <FORM:0749715/IV(a)/1> (wherein R is an alkyl or aralkyl group) with b -amino-ethyl benzyl sulphide. This process may be combined with the further step of hydrogenolysing the product with sodium in liquid ammonia to obtain pantetheine or, where special precautions to avoid oxidation are not taken, pantethine, or with the further step of treating the S-benzyl pantetheine with dibenzylchlorophosphonate and eliminating the benzyl groups from the resulting S-benzyl-pantetheine 41-(dibenzyl phosphate) by hydrogenolysis with sodium in liquid ammonia to obtain pantetheine 41-phosphate. The anhydride of the above general formula, which is stated to be unstable and is therefore preferably used in the medium in which it is formed, may be prepared by reacting a trialkylammonium or N-alkyl morpholinium salt of pantothenic acid with an alkyl or aralkyl chloroformate. The reaction of the anhydride with b -amino ethyl benzyl sulphide is preferably carried out in a solvent, such as dimethyl formamide or tetrahydrofuran, and it is preferred to use a solution of the sulphide, for example in chloroform. In a modification of the process the reaction is carried out in the presence of a molar equivalent of a trialkylamine. The reaction temperature is initially at 0 DEG C. or below and the reaction is completed at room temperature. Examples illustrate each of the above processes and in addition describe (1) the formation of the triethylamine, tributylamine and N-methyl morpholine salts of pantothenic acid, itself obtained from calcium pantothenate and oxalic acid; (2) the successive passage of the reaction mixture from the hydrogenolysis of S-benzyl pantetheine through cation and anion exchange resins, or its passage through a cation exchange resin followed by elution from a column of alumina; (3) the preparation of dibenzyl chlorophosphonate from dibenzyl phosphite and N-chlorosuccinimide and the isolation of pantetheine 41-phosphate as the barium or calcium salt after purification of the reaction mixture of S-benzyl-pantetheine-41-(dibenzyl phosphate) by passage through a cation exchange resin.