INTRODUCTION 627 



position, the normal configuration on this carbon is a necessary condition 

 for activation. Thus, isopyrocalciferol, which differs from ergosterol only 

 in the position of the Cg carbon, cannot be activated to produce a potent 

 vitamin D.^ Lumisterol, however, in which an epimerization of the methyl 

 group at Cio poses the only structural difference from ergosterol, is fully ac- 

 tivatable.2 Apparently the 9 position but not the 10 position determines 

 the potential activity. 



The side-chain is an important determinant of activity. The sex hor- 

 mone, 3,17-dihydroxyandrostadiene, which is structurally similar to ergos- 

 terol and 7-dehydrocholesterol except that it contains no side-chain and 

 has a hydroxyl group on carbon-17, was shown by Dimroth and Paland*- to 

 be inactive as a precursor of vitamin D. Furthermore, Haslewood*^ found 

 that the cholanic acid analogues of ergosterol and of 7-dehydrocholesterol, 

 which are similar to the provitamins D2 and D3 except that they have a 

 shorter side-chain, have practically no activity. The side-chain can be 

 modified by desaturation or saturation between C22 and C23 without seri- 

 ously lowering the effectiveness of the sterol as a provitamin D. This has 

 been demonstrated not only in the case of 22-dihydroergosterol, as con- 

 trasted with ergosterol, but also with the natural compound, A^-'^-^^-choles- 

 tatriene-3-ol (22-dehydro-7-dehydrocholesterol). Presumably it is present 

 in the provitamin D mixture of the edible sea mussel {Mytilis edulis)f* 

 it is questionable whether or not it contributes to the potency of the irra- 

 diated mixture.^* 



It is evident that a large number of compounds may serve as potential 

 provitamins D. As early as 1935, Bills^^ had recognized this fact; he first 

 estimated that there were six such compounds ;^^ this was later revised to 

 eight.^^ In addition to the three most active provitamins D already men- 

 tioned, namely ergosterol, 7-dehydrocholesterol,^^ and 22-dihydroergostero], 

 the additional active compounds include 7-dehydrositosterol,^^ 7-hydroxy- 

 cholesterol and 7-dehydrocampesterol, as prepared by Ruigh.^^ Although 

 7-dehydrostigmasterol differs from ergosterol only by ha\'ing an ethyl group 

 in the C24 position in place of the methyl group in ergosterol, it is practi- 

 se K. Dimroth and J. Paland, Ber., 72, 187-190 (1939). 



83 G. A. D. Haslewood, Biochem. J., 38, 454-456 (1939). 



8^ J. van der Vliet, Rec. trav. chim., 67, 246-256, 265-281 (1948). 



^ C. E. Bills, Cold Spring Harbor Symposia Quant. Biol., 3, 328-340 (1935). 



^ C. E. Bills, Paper presented at convention Am. Med. Assoc, Kansas City, May 14, 

 1936; cited bv C. E. Bills, O. N. Massengalo, M. Imboden, and H. Hall, /. Nutrition, 13. 

 435-452(1937), p. 435. 



" E. Geiger and S. Lassen, Proc. Soc. Exptl. Biol. Med., 52, 11-12 (1934). 



88 W. Wunderlich, Z. phy.siol. Chem., 24I, 116-124 (1936). 



89 W. L. Ruigh, J. Am. Chem. Soc, 64, 1900-1902 (1942). 



