724 VII. VITAMINS A 



(11) Other Syntheses of Vitamin A 



Cawley et al.^^^ have prepared crystalline vitamin A by methods which 

 the authors state differ from any heretofore described in the literature. 

 Vitamin A acetate and vitamin A anthraquinone carboxylate have been so 

 synthesized, and are reported to be identical with similar esters prepared 

 from the natural product. Such methods are presumably the basis for the 

 procedures employed in the large-scale synthesis of vitamin A now being 

 developed commercially. Details of the synthesis have not as yet been 

 published. 



Hunter and Williams ^^^ have succeeded in preparing vitamin A from /3- 

 carotene by chemical methods, by oxidative fission of the central double 

 bond of ^-carotene with hydrogen peroxide to yield vitamin A aldehyde, 

 and subsequent reduction to vitamin A alcohol by the Pondorff method. 

 The maximum yield obtained was only 0.4 to 0.5%. Vitamin A was identi- 

 fied by the antimony trichloride reaction and by its transformation to 

 cyclized vitamin A with AV30 alcoholic hydrogen chloride. 



No synthesis has been successful so far for vitamin A2, and none can be 

 expected until its structure is proved. One cis stereoisomer of vitamin A 

 has been prepared from fish liver oils by Robeson and Baxter. ^^'^^ Presum- 

 ably, this and other cis compounds of vitamin A can be synthesized by 

 catalysts such as iodine, employed by Zechmeister.^^* 



{!£) Syntheses of Homologaes of Vitamin A Ethers 



Several homologues of vitamin A have been synthesized which possess a 

 rather high degree of biopotency. The ])rincipal compounds which have 

 been investigated in this study are 5-dehydrohomovitamin A ethyl ether 

 (XLVI) and homo vitamin A ethyl ether (XLVII). Each of these com- 

 pounds has one additional carbon atom at the end of the side chain. 



Both of these homologues are readily prepared by two quite similar pro- 

 cedures. In both cases the aldehyde formed by decarboxylation of glycidic 

 acid (V) is the starting point. The methods which have been Avorked out 

 by Milas,i^2 ^iwd by Milas, Lee, et al.,"^ involve the condensation of the 

 aldehyde with either 3-methyl-6-ethoxyhexa-l-yn-3-ol (XLII) or 3-methyl- 

 6-ethoxyhexa-3-en-l-yne-l (XLIII). In the first case the glycol (XLIV) is 

 formed as the intermediate, while in the second instance the carbinol 

 (XLV) is formed. These syntheses are diagrammed on page 725. 



*i« J. D. Cawley, C. D. Robeson, L. Weisler, E. M. Shantz, N. D. Embree, and J. G. 

 Baxter. Presented before the American Chemical Society Meeting in New York Citj', 

 Sept., 1947, p. 26c. 



