146 VITAMIN D GROUP 



produced is of lesser potency.^®' ^^ When the double bond is replaced by an 

 oxido group, as in 22,23-oxidoergosterol, the activatability is sharply re- 

 duced."^ 



7-Dehydrocampesterol is a C-24 epimer of 22-dihydroergosterol.**' ®^ It 

 is about one-tenth as activatable as ergosterol, being in this respect some- 

 what inferior to 22-dihydroergosterol. Thus it appears that the difference 

 in antiricketic activity due to stereoisomerism on C-24 is somewhat greater 

 than the difference caused by the double bond at C-22. 



The presence of an ethyl group at C-24, as in 7-dehydrostigmasterol, 

 instead of a methyl group as in ergosterol, apparently destroys activata- 

 bility.^^ An ethyl group at C-24 is present in 7-dehydrositosterol, which in 

 early experiments was found to be activatable.^^- " Ruigh,^^ however, has 

 presented evidence that the observed activatability is due to the presence 

 in the 7-dehydrositosterol of a quantity of 7-dehydrocampesterol or other 

 provitamin D as an impurity. 7-Dehydroclionasterol, the C-24 epimer of 

 7-dehydrositosterol, has not been tested for activatability, but in consider- 

 ation of the presence of the ethyl group, one would not expect it to acquire 

 marked antiricketic properties. 



Several of the biological tests for the activatability of the sterols in Fig. 6 

 leave much to be desired. In most instances the irradiated products were 

 tested only on rats, and only by oral administration. The conclusions in 

 regard to the relation of chemical structure to antiricketic activatability 

 might have to be modified if the products were tested at higher dosage 

 levels, or by parenteral administration, or with a larger number of species. 

 One is reminded that, if it were customary to use only chicks in testing 

 vitamin D, irradiated ergosterol would be found inactive, or, at most, 

 feebly active, in comparison with irradiated 7-dehydrocholesterol. The ques- 

 tion mark is therefore applied to some sterols in Fig. 6, even though the 

 best reported tests have indicated that their irradiation products do not 

 cure rickets. 



4. Newer Synthetic Methods 



The provitamins D, especially 7-dehydrocholesterol, are so important 

 commercially that much effort has been applied to improving the original 

 synthesis^^ and to devising new procedures for dehydrogenating common 

 sterols. Windaus and Schenck''" patented the original procedure as applied 

 to cholesterol, sitosterol, and stigmasterol and offered zirconium and mag- 

 nesium alcoholates as alternatives to aluminum isopropylate for the re- 

 's F. G. McDonald, /. Biol. Chem. 114, Proc. Ixv (1936). 



67 W. Grab, Hoppe-Seyler's Z. physiol. Chem. 243, 63 (1936). 



68 E. Fernholz and W. L. Ruigh, /. Am. Chem. Soc. 63, 1157 (1941). 

 "s W. L. Ruigh, J. Am. Chem. Soc. 64, 1900 (1942). 



70 A. Windaus and F. Schenck, U. S. Pat. 2,098,984 (1937). 



