II. CHEMISTRY 597 



Its calcium salt is also dextrorotatory [af^ + 24.3. It has an ionization 

 constant of about 3.9 X ICh^^*"' ^' 



C. CONSTITUTION 



Pantothenic acid has the empirical formula C9H17O5N. It consists es- 

 sentially of two compounds, pantoic acid and /S-alanine, combined in acid- 

 amide linkage by the coupling of the carboxyl group of pantoic acid with 

 the amino group of /S-alanine. It has been assigned the following structure. 



CH3 



I 

 HOCH2— C— CHOH— CO— NH— CH2— CH2— COOH 



CH3 



a-7-Dihydroxy-/3, |S-dimethyl butyryl-/3-alanine 



Pantoic acid has two hydroxy groups, one of them in the a- and the other in 

 the 7 position. In acid solution, especially upon heating, it forms a lactone 

 which is represented by the following structure.^"- ■*"■ ^^ 



CH3 

 CH2— C— CHOH— C = O 

 CH3 

 O 



a-Hydroxy-/3,i3-dimethyl-7-butyrolactone'' 



D. SYNTHESIS 



A partial synthesis of pantothenic acid was effected before its struc- 

 ture was known. The total synthesis of pantothenic acid involves essentially 

 the synthesis of pantoic acid or its lactone followed by its condensation 

 with /3-alanine. The synthesis of pantoic acid is carried out as follows.*^ 

 Isobutyraldehyde is condensed with formaldehyde to give Q:,Q:-dimethyl- 

 (8-hydroxy-propionaldehyde. This compound is condensed with hydro- 

 cyanic acid or potassium cyanide in the presence of calcium chloride to 

 form racemic a: -hydroxy -/3,/3-dimethyl-7-butyrolactone. This lactone may 

 then be condensed with /3-alanine to form racemic pantothenic acid. Both 

 the racemic pantothenic acid and the pantoic lactone can be resolved by 

 the fractional crystallization of their quinine salts.^^ The salts of quinine 

 methohydroxide, quinidine methohydroxide, and cinchonine methohy- 

 droxide have also been used to resolve racemic mixtures of these com- 

 pounds.^"- ^^ 



Many methods are available for the condensation of pantoic lactone with 

 i3-alanine. A simple and effective method is the direct condensation of 



