CHEMICAL CONSTITUTION AND SYNTHESIS 



Mitchell ei al.^ and by Stiller et al.* In the first of these papers, the 

 non-^-alanine fraction of the pantothenic acid molecule was shown to 

 contain an a-hydroxyl group, since it yielded formic acid on hydrolysis 

 with sulphuric acid, and carbon monoxide on dehydration with sul- 

 phuric acid at 140° C. Since the acid lactonised spontaneously, it 

 probably contained a y-hydroxyl group as well, and the absence of a 

 jS-hydroxyl group was presumed from the formation of an unsaturated 

 derivative of the type R . CH : CH . COOH on dehydration, and the 

 fact that oxidation with lead tetra-acetate, periodic acid or hypoiodite 

 did not destroy the activity, as it would have done had the substance 

 been an aj8-glycol. Accordingly, the following a-hydroxy-y-lactones 

 were synthesised and coupled with j8-alanine : a-hydroxy-y-valero- 

 lactone, a-hydroxy-jS-methyl-y-butyrolactone and a-hydroxy-a-methyl- 

 y-butyrolactone. The products showed definite, but slight, physio- 

 logical activity when tested on Streptococcus lactis (which is unaffected 

 by excess jS-alanine). 



In the second of the papers, the lactone obtained on acid hydrolysis 

 was purified by molecular sublimation and obtained pure, m.p. 92 to 

 93° C, [a]!^" = 49'8. It had the empirical formula, CgHioOa- It 

 was, therefore, a derivative not of valeric acid as had been assumed 

 previously but of caproic acid. It contained one active hydrogen 

 atom and yielded an acetate, dinitrobenzoate and ^-nitrobenzoate. 

 A Kuhn-Roth determination gave a result equivalent to 26 % of 

 C-methyl group, indicating the presence of a ^^w-dimethyl group. 

 This was confirmed by the formation of acetone on treatment with 

 barium permanganate. The conclusion that the lactone was a-hydroxy- 

 jS^-dimethyl-y-butyrolactone was established by the following series of 

 degradations : 

 CH3 CH3 

 CH2 . C . CHOH . CO £!5!^ CH2OH . C . CHOH . C(OH)(CeH6)2 > CO{C^U,)^ 



CH3 CH 



CHaMgl 

 CH3 CH3 CH3 



CH2OH . C . CHOH . C(OH)(CH3)2 > CH^OH . C . CHO > CH^OH . C . COOH 



CH3 CH3 CH3 



Natural pantolactone is laevorotatory, whereas pantoic acid is dextro- 

 rotatory. 



The partial synthesis of pantothenic acid from this lactone and 

 j3-alanine ethyl ester or, better since this avoided hydrolysis of the 

 pantothenic ester, by heating the lactone with the sodium salt of 

 J8-alanine, was described by R. J. Williams et al.^ and by S. H. Babcock 



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