698 VII. VITAMINS A 



TABLE 9 

 Comparison of the Properties of Vitamin A and of Neovitamin A" 



Physical property or reaction Vitamin A Neovitamin A 



Crystal form Yellow prisms Yellow needles 



Melting point , "C 62-64 58-60 



Melting point of phenylazobenzoate, °C 79-80 94-96 



Melting point of authraquinone j3-carboxylate, °C... 121-122 134-136 (red) 



X max., niM 324-325 328 



£; (1%, 1 cm.) 1740 (325 m^) 1645 (328 mu) 



Resistance to atmospheric oxidation Less More 



Rate of maleic anhydride addition Rapid Slow 



Rate of dehydration with alcoholic HCl Rapid Slow 



° Adapted from C. D. Robeson and J. G. Baxter, /. Am. Chem. Soc, 69, 136-141 

 (1947). 



In the case of the natural fish hver oils, the neovitamin A is believed to be 

 a cis isomer. This conclusion is based upon the fact that cis isomers have 

 lower melting points than those of the corresponding ^rans compounds/^^ 

 that they have lower extinction coefficients at their absorption maxima, ^^^ 

 and, finally, that they add maleic anhydride more slowly. ^^^ The cis 

 bond- is assigned to the 5 position, since the only other double bond which 

 can undergo steric rearrangement is trans in all the commonly occurring 

 carotenoids. The crystals of neovitamin A p-phenylazobenzoate con- 

 trasted with vitamin A p-phenylazobenzoate are shown in Plate 4, while 

 the crystals of neovitamin A and vitamin A are compared in Plate 5. 



Neovitamin A and all-//a/i6-\itamin A have been considered to possess 

 approximately the same biological potency.^' However, the recent investi- 

 gations of Harris et al?^^" have given a figure of 85.3% for neovitamin A, 

 as compared with the &\\-trans isomer, when the calculations were based 

 upon the U.S. P. XHl growth method; the value as determined by the 

 liver storage test was 75.6%. Since the E (1%, 1 cm.) of pure aW-trans- 

 vitamin A at 325 m^i is 1740. while that of the neo form is 1645 at 328 

 mM. the biopotencies obtained b.y these methods would be revised to 80.7 

 and 71.5% on the molar ])asis. Harris, Ames, and Brinkman^^^" calculated 

 that, in terms of U.S. P. units, which are based upon the rat-growth method, 

 the biopotency of neovitamin A is 2,690,000 U.S. P. units per gram. The 

 interconversion in vivo of one form to the other was likewise demonstrated 

 by these workers. ^^^° 



1" L. Zechmeister, Chem. Revs., 34, 267-344 (1944). 



>54 H. P. Koch, Chemistry & Industry, 20, 273-275 (1942). 



155 R. S. Morrell, T. R. Bolam, W. R. Davis, S. Marks, E. O. Phillips, and W. S. Sim, 

 Trans. Faraday Soc, 38, 362-366 (1942). 



"*" P. L. Harris, S. R. Ames, and J. H. Brinkman, J. Ain. Chem. Soc, 73, 1252-1254 

 (1951). 



