GB535988A - Pantothenic acid and similar growth-promoting substances - Google Patents

Abstract

535,988. Peptides of # - alanine ; lactones. MERCK & CO., Inc. March 27,1940, No. 5484. Convention date, April 3, 1939. [Class 2 (iii)] Pantothenic acid and similar peptides of #-alanine, which are growth promoting-substances, are made by reacting #-alanine or a salt or ester thereof with an α-keto-or α-hydroxyacid or with the corresponding lactone ; the product being hydrolyzed, if necessary, to produce the free acid. In examples (1) α-hydroxy- γ-n-valerolactone is reacted at 30‹C. with #-alanine ethyl ester and the product hydrolyzed with sodium carbonate solution, a compound of the formula is obtained, (2) α-hydroxy-#-methyl-γ-n-butyrolactone is similarly reacted with #-alanine ethyl ester, (3) the lactone obtained by hydrolysis with hydrochloric acid of the crude calcium salt of the pantotheric acid derived from sheep's liver by the process described by Williams and others (J. Am. C. S., vol 60, p. 2719) is similarly reacted with #-alanine ethyl ester. Other esters or salts of #-alanine may be used instead of the ethyl ester, and other lactones, e.g. α-keto-γ-valerolactone. Lactones :-α-Hydroxy-γ-n-valerolactone is made by treating aldol with hydrogen cyanide and hydrolyzing the nitrile obtained. α- hydroxy-#-methyl-γ-n-butyrolactone is made by condensing propionaldehyde with formaldehyde, converting into the nitrile and hydrolyzing. Other lactones of α-hydroxy acids may be obtained by a similar method, or they may be made from lactones containing one less carbon atom by reduction, addition of HCN and hydrolysis ; thus butyrolactone may be converted into α-hydroxy-#-hydroxy-valeric acid or the corresponding lactone. α-keto-lactones may be made from si mple lactones wi th one less carbon atom by treating with phosphorus pentachloride, and converting the acid chloride thereby formed into the nitrile of an α-keto chlorine-substituted acid by treating with cuprous cyanide ; the nitrile is then hydrolyzed and converted to the lactone by treatment with moist silver oxide. The α:-keto-lactones may also be made by condensing the simple lactones with di-ethyloxalate and de-carboxylating the product.