II. CHEMISTRY 143 



several vaguely recognized bodies from which antiricketic materials have 

 been obtained by irradiation or other treatment; these will be discussed 

 under Minor and Obscure Forms of Vitamin D. 



3. Chemical Structure and Activatability 

 a. The Hydroxyl Group at C-3 



It has long been established that certain esters of crude cholesterol, i.e., 

 of 7-dehydrocholesterol, are made antiricketic by irradiation. These include 

 the acetate,^^' *^' ^^ benzoate,^^ isobutyrate," palmitate,^^ and phosphate 

 (monocholesteryl) .^^ Ergosterol esters undergo the chemical changes of acti- 

 vation as readily as the free sterol. However, the esters of calciferol which 

 are formed by the irradiation of the corresponding esters of ergosterol are 

 not uniformly effective when administered to rats. Irradiated ergosteryl 

 acetate,"' ^* irradiated ergosteryl ethyl carbonate,^^ and irradiated dier- 

 gosteryl phosphate*^ are as effective as irradiated ergosterol. The irradiated 

 benzoate was at first claimed to be as effective'^^ as irradiated ergosterol but 

 later was found to be considerably less effective. ^^' ^^^ The palmitate is also 

 less effective.^^^' ^^ The allophanate, cinnamate, diphenylacetate, oxalate, 

 a-naphthylure thane, and phenylurethane are inactive at the usual curative 

 levels. ^^* The differences in antiricketic effectiveness are due merely to 

 differences in the assimilability of the esters, for by saponification the full 

 effectiveness of the vitamin D in any of the esters can be brought out. This 

 phenomenon has also been observed in the natural vitamin D esters of 

 fish oils.^" 



When the hydroxyl group in 7-dehydrocholesterol is replaced by halogens, 

 the molecule is considerably stabilized. The chloride and bromide of this 

 provitamm D undergo changes upon exposure to ultraviolet rays which 

 indicate spectrographically that the corresponding halides of vitamin D3 are 

 formed. These halides, which are resistant to saponification, are devoid of 

 antiricketic action when fed to rats and chicks, even in large doses. ^^ Com- 

 pounds such as these, where the structure is present but the activity hidden, 

 raise the poser: "When is a vitamin not a vitamin?" 



" A. F. Hess, M. Weinstock, and E. Sherman, J. Biol. Chem. 67, 413 (1926). 



" C. E. Bills and F. G. McDonald, /. Biol. Chem. 72, 13 (1927). 



"H. von Euler and A. Bernton, Ber. 60, 1720 (1927). 



" O. Rosenheim and T. A. Webster, Lancet II, 622 (1927). 



" R. K. Callow, Biochem. J. 25, 79 (1931). 



" H. von Euler, A. Wolf, and H. Hellstrom, Ber. 62, 2451 (1929). 



"*' A. Windaus and O. Rj^gh, Nachr. Ges. Wiss. Gottingen, Math, physik. Kl. 202 



(1928). 

 «" B. E. Bailey, /. Fisheries Research Board Can. 6, 103 (1943). 

 " S. Bernstein, J. J. Oleson, H. B. Ritter, and K. J. Sax, J. Am. Chem. Soc. 71, 2576 



(1949). 



