Synthesis and properties of pantothenic acid monophosphates.

Although it appears most probable that coenzyme A is a phosphate derivative of pantothenic acid (2), little information is available as to the position or nature of the phosphate linkage in the molecule. It became of interest in this connection to examine the properties of simple phosphate derivatives of pantothenic acid, and for this purpose efforts were directed toward the preparation of the (Yand y-monophosphates (VI and IV, respectively, Diagram 1). Synthesis of the CY compound, VI, was undertaken by condensing pantolactone phosphate (V) or its diphenyl derivative (3) with /3-alanine. Unfortunately, although a variety of conditions were tried, the yields were very low, and the desired product was not obtained in pure form. The crude product contained no free pantothenic acid, but did show typical bound pantothenic acid activity; that is, it was inactive as such for Lactobacillus arabinosus, but became active after phosphatase treatment. Since the starting materials did not possess such activity, it is quite certain that the a-phosphate, VI, was present. The y-phosphate, IV, was obtained during attempts to prepare a diphosphate (1). It was observed that reaction of free pantothenic acid with diphenyl chlorophosphonate led to a monophosphate derivative, whereas methyl pantothenate, under the same conditions, yielded a diphosphate (4). Apparently one of the hydroxyl groups of free pantothenic acid is in some way masked, and therefore it is not available for phosphorylation. Since it has also been noted that direct titration of the free acid gives an alkali consumption of less than one-half of the theoretical amount,’ it was concluded that one of the hydroxyls, most probably the a, exists in lactone