SYNTHESIS OF VITAMINS D 71)1 



CH, 

 H, I ' 



,< CHj ^ CH 



/ \T J H/ \ 



H? C C C CHg 



Ho CH, I I I I 



HzC C C \ HC. 



HOsI I i ^^ IXHzCHj 



;a ,a ,ch ch 



H, H 



2XM 



Vitamin Ds 



(5) General Smichiral Rcquiremenif^ for the Vitamins D 



On the basis of the known constitution of vitamins D2 and D3, and of the 

 knoAMi structure of other provitamins, it is generally agreed that certain 

 structural requirements must obtain for \ itamin D activity. A compound 

 of this nature must be a derivative of a steroid in which the B ring is nip- 

 tured between carbons 9 and 10. There is also a requirement that three 

 conjugated double bonds exist at the 10,18-, 5,6-, and 7,8-positions. The 

 hydroxyl group on carbon 3 is another prerequisite. Vitamin D activity 

 occurs only where the alcohol group is free, or in the esters which can be 

 hydrolyzed in the organism. Non-hydrolyzable esters and ethers of vit- 

 amin D are inactive. ^^^ Epimerization of the hydroxyl group also greatly 

 alters the biological activity, although the effectiveness is not entirely lost 

 in the case of activated epi-7-dehydrocholesterol. 



Another requirement for biological activity is the presence of a chain at- 

 tached at carbon 17. The absence of the side chain (as in 5,7-androstad- 

 iene-3,17-diol),^^'*^ or even the presence of a four-membered chain such as 

 occurs in activated 3-hydroxy-5,7-choladienic acid,*^ practically inactivates 

 the compound. Even slight changes in the normal side chains in the 

 naturally occurring sterols are accompanied by marked alterations in 

 biological potency. 



5. Synthesis of the Vitamins D 



Although considerable information is available concerning methods for 

 the synthesis of the vitamins D by activation of their provitamins (see Sec- 

 tion C), no complete synthesis of any members of the vitamin D group has 

 been accomplished. Milas and Alderson (XXXVIII), ^''^ Dimroth 

 (XXXIX), 2«^. 265 and Aldersley and Burkhardt (XL^ have synthesized 



^'^^ A. Windaus and O. Rygh, Nachr. Ges. Wiss. GoUingen, Math, physik. Klasse, III, 

 202-216 (1928). 



''^ N. A. Milas and W. L. Alderson, /. Am. Chem. Soc, 61, 2534-2537 (1939). 



2" K. Dimroth, Ber., 71, 1333-1345, 1346-1350 (1938). 



2« K. Dimroth and H. Jonsson, Ber., 71, 2658-2662 (1938). 



2's J. B. Aldcrslev and G. N. Burkhardt, ./. Chem. Soc, 193S, 545. 



