756 VIII. PROVITAMINS D AND VITAMINS D 



4. Synthesis of the Provitamins D 



None of the provitamins D has been completely synthesized, although 

 several of them have been prepared from closely related sterol compounds. 

 The preparation of the 7-dehydro compounds has been the most involved, 

 but a similar procedure may be followed in preparing these from the ap- 

 propriate 7-dihydrosterol. 



(/) 7-Dehy(lrocholesterol 



Windaus, Lettre, and Schenck^* have accomplished an entirely satis- 

 factory synthesis of 7-dehydrocholesterol (XVII) from cholesterol (VI). 

 In this method, cholesteryl acetate (XII) is oxidized by chromic acid to 7- 

 oxo-cholesteryl acetate (XIII). When this is treated with aluminum iso- 

 propoxide in isopropanol, 7-hydroxycholesterol (XIV) is formed. As a re- 

 sult of a simultaneous ester interchange, the free alcohol is obtained. 

 After benzoylation of the dihydroxy compound, the dibenzoate (XV) is 

 thermally decomposed into the monobenzoate of 7-dehydrocholesterol 

 (XVI), a molecule of benzoic acid being simultaneously freed. On saponi- 

 fication, provitamin D3 is set free (XVII). 



Another synthesis involves the use of cholesterol benzoate as the starting 

 material. ^^^ The 7-hydroxycholesterol can be converted into the 7-dehy- 

 dro compound by the utilization of amines, ^^^-^^^ whereby isodehydro- 

 cholesterol is obtained as a by-product. ^•^'' Less satisfactory methods in- 

 volve direct oxidation of cholesterol by means of mild oxidants ^^^ such as 

 peroxides, the use of quinones as dehydrating agents, ^^®'^*^ and also the ap- 

 plication of succinodehydrogenase in the presence of light. ^^"^ 



{2) 22-Dihydroergosterol 



22-Dihydroergosterol, or provitamin D4, has been prepared by Windaus 

 and Langer^^ by hydrogenation of the side chain of ergosterol. This can 

 readily be accomplished by first acetylating the hydroxyl group, and then 

 protecting the double bonds at the 5,6 and 7,8 positions by formation of the 

 addition product with maleic anhydride. After catalytic hydrogenation, 

 the maleic anhydride is removed by heat, and the free provitamin may be 

 obtained after saponification of its ester. 



1" H. R. Rosenberg and J. M. Tinker (to E. I. du Pont de Nemours & Co.), U. S. 

 Patent No. 2,215,727 (Sept. 20, 1940). 



"2 G. A. D. Haslevvood, J. Chem. Soc, 1938, 224-228. 



133 H. R. Rosenberg (to E. I. du Pont de Nemours & Co.), U. S. Patent No. 2,209,934 

 (July 30, 1940). 



134 A. Windaus, O. Linsert, and H. J. Eckhardt, Ann., 534, 22^1 (1938). 



13* J. Waddell, U. S. Patent Nos. 2,028,364 (May 16, 1933), and 2,056,992 (Oct. 13, 

 1936). 



i3« N. A. Milas and R. Heggie, /. Am. Chem. Soc, 60, 984-985 (1938). 

 137 p p, T. Sah, Rec. trav. chim., 59, 454-460 (1940). 



