PANTOTHENIC ACID 621 



hydroxy-/? -methyl -/?-methylolvaleryl) -^-alanine ("methylpantothenic 

 acid") are the most effective in replacing the nutritional requirement of 

 pantothenic acid for a wide variety of organisms. The "methylpantothenic 

 acid" appears to be somewhat mqre active than "hydroxypantothenic 

 acid" for several organisms, but neither of the substituted pantothenic 

 acids exerts an action comparable with that of the vitamin on a wide 

 variety of organisms. In many instances, the activity of the analogue 

 compared with that of the vitamin is greater at low than at high dosage. 



Preparation of two of the four diastereoisomers of "methylpantothenic 

 acid" has recently been reported. 25 DL-a-Keto-/3-methyl-/?-methylolvalero- 

 lactone was resolved into the two optically active forms which were 

 reduced to the corresponding a-hydroxy lactones by yeast. Since yeast 

 reduces cc-keto-/3,/?-dimethylbutyrolactone to ( — ) -pantolactone, 26 the two 

 optically active homologues of pantolactone presumably have the same 

 D-configuration on the a-carbon, and the two disastereoisomeric "methyl- 

 pantothenic acids" prepared from these lactones differ only in configura- 

 tion on the /3-carbon and have a configuration analogous to pantothenic 

 acid on the a-carbon. The "methylpantothenic acid" A with a configura- 

 tion on the /3-carbon presumably similar to alloisoleucine determined by 

 analogy in melting points is 27.8 per cent as active as pantothenic acid. 

 The "methylpantothenic acid" B, presumably with configuration similar 

 to isoleucine, is 62.5 per cent as active as pantothenic acid. Tested at a con- 

 centration of 14 y per cc of cinchonidine salt, neither of these diastere- 

 oisomeric "methylpantothenic acids" allowed a maximum growth response 

 of Streptobacterium plantarum 10 S in the absence of pantothenic acid. 25 



Since DL-N-(a-hydroxy-^-ethyl-^-methylolvaleryl) -^-alanine is in- 

 active, 12 apparently only one of the ^-methyl groups of the butyryl por- 

 tion of pantothenic acid can be modified without complete loss of the 

 biological activity of the vitamin. 



All the analogues capable of replacing pantothenic acid to any extent 

 retain at least one of the two hydroxyl groups. Modifications in vivo 

 may account for the activity of a number of the less effective analogues. 



Some analogues of pantothenic acid which are inhibitory have been 

 found to replace pantothenic acid partially. These will be discussed 

 separately. 



The alcohol corresponding to pantothenic acid (pantothenyl alcohol) 

 has been found to be as effective as pantothenic acid in preventing 

 achromotrichia in rats. 16 However, this activity is the result of conver- 

 sion of the alcohol in vivo to pantothenic acid. 17 Other warm-blooded 

 animals have been found to carry out this oxidation. 17 After administra- 

 tion of pantothenyl alcohol, pantothenic acid was excreted in the urine 

 of male human subjects in amounts equal to or slightly greater than after 

 administration of an equivalent amount of calcium pantothenate (100 



