METABOLISM OF CAROTENOIDS AND VITAMINS A 551 



The usual type is the all-/rans form. Graham et al.^^^ synthesized the 3-czs 

 isomer by the same sequence of reactions as those used for the synthesis of 

 the all-/rans form. 5-czs- Vitamin A aldehyde (also called neoretinene) can 

 be prepared by the oxidation of neovitamin A alcohol with manganese 

 dioxide.^i^ Graham and co-\vorkers^'^ reported that the biopotency of 3- 

 cis vitamin A aldehyde is the same as that of vitamin Ai. 



Hubbard and co-workers^-° characterized five different retinenes which 

 are cis-irans to one another. This number of isomers is possible only if a 

 "forbidden" cis linkage occurs, i.e., one which, because of steric hindrance, 

 was believed to be impossible. There are indications that, under some con- 

 ditions, stable compounds can be made with these "hindered" cis 

 bonds.^-^'^-2 Collins and co-workers^-^ demonstrated the in vitro regenera- 

 tion of rhod opsin when synthetic vitamin A and a phosphate buffer were 

 used with a preparation from rat retinae and choroids. 



(c) Vitamin A Ethers. Vitamin A methyl ether was first prepared from 

 vitamin A alcohol by Hanze and collaborators,^-'' in 1946. It is a light 

 yellow solid which has a biologic potency of 3,000,000 U.S.P. units per 

 gram. Other data on vitamin A methjd ester are included in the papers of 

 Oroshnik,*'^ and of Isler et al.^-^ 



Homovitamin A ethyl ether (C21H31OC2H5) and 5-dehydrohomovitamin 

 A ethyl ether (C21H29OC2H5) are two biologically active synthetic com- 

 pounds, each of which has one more carbon atom on the aliphatic side- 

 chain than the number present in vitamin A. These compounds have 

 been synthesized by Milas and associates.^^^ 5-Dehydrohomovitamin A 

 ethyl ether is readily changed to homovitamin A ethyl ether by reduction 

 with palladium in the presence of calcium carbonate. Both compounds 

 possess slight biologic activity, since they are able to cure xerophthalmia 

 and to produce normal growth of vitamin A-depleted rats. However, the 

 biopotenc}^ is small in view of the high doses required,^-* namely 96 mg. and 



818 W. Graham, D. A. van Dorp, and J. F. Arens, Rec. trav. chim., 68, 609-612 (1949). 

 8" P. D. Dalvi and R. A. Morton, Biochem. J., 50, 43-48 (1951). 



820 R. Hubbard, R. I. Gregerman, and G. Wald, /. Gen. Physiol, 36, 415-429 (1953). 



821 C. H. Eiigster, C. F. Garbers, and P. Karrer, Helv. Chim. Acta, 36, 1378-1383 

 (1953). 



822 C. F. Garbers and P. Karrer, Helv. Chim. Acta, 36, 828-834 (1953). 



823 F. D. Collins, J. N. Green, and R. A. Morton, Biochem. J., 53, 152-157 (1953). 



824 A. R. Hanze, T. W. Conger, E. C. Wise, and D. I. Weisblat, /. Am. Chem. Soc, 68. 

 1389 (1946). 



825 W. Oroshnik, /. Am.. Chem.. Soc, 67, 1627-1628 (1945). 



826 O. Isler, M. Kofler, W. Huber, and A. Ronco, Experientia, 2, 31 (1946). 



827 N. A. Milas, S. W. Lee, C. Schuerch, Jr., R. O. Edgerton, J. T. Plati, F. X. Grossi, 

 Z. Weiss, and M. A. Campbell, /. Am. Chem. Soc, 70, 1591-1596 (1948). 



828 R. S. Harris; cited by N. A. Milas, Vitamins and Hormones, 5, 1-38 (1947). p. 5. 



