II. CHEMISTRY AND INDUSTRIAL PREPARATION 25 



tene may easily disproportionate in vivo to give one molecule of vitamin A 

 and one molecule of \^tamin A aldehyde. The latter could easily be reduced 

 in vivo to vitamin A. Such an hypothesis can find ample support in the re- 

 cent Iwdroxylation experiments of jS-carotene.^"® 



15 15 enzyme 



Ci9H27CH=CH— C:9H27 + noon > CiJIotCH— CH— CgHaT 



I I 



OH OH 



XLV 

 XLV -» CsHovCHoOH + CiJIstCHO + 2H -^ 2C19H27CH2OH 



A slightly different oxidative cleavage has been proposed by Hunter/' 

 who assimied that /3-carotene is cleaved in vivo to give two molecules of 

 \'itamin A aldehyde which are subsequently reduced to two molecules of 

 vitamin A. 



Attempts to duplicate the cleavage of /3-carotene in vivo using biochemical 

 methods produced doubtful results.-*^ 



For a long time even chemical methods, as shown under Section II. A. 4, 

 failed to cleave j8-carotene symmetrically. Using hydrogen peroxide in a 

 chloroform-acetic acid solution, Hunter and Williams^ were the first to 

 achie^•e the symmetrical cleavage of jS-carotene, although the yields of vi- 

 tamin A aldehyde obtained were small (0.4 to 0.5%). It had already been 

 known for some time" that hydrogen peroxide in non-aqueous solvents 

 causes an efficient hydroxylation of double bonds in the presence of small 

 amounts of osmium tetroxide, so Goss and McFarlane^ used this method 

 to effect the cleavage of |S-carotene. They claimed that a hypothetical in- 

 termediate was formed which upon treatment with alkali produced vitamin 

 A directly. This reaction w^as studied more thoroughly by Wendler et al.,^ 

 who reported the isolation of vitamin A aldehyde, /3-ionylidene acetalde- 

 hyde, and 2,7-dimethyloctatriendial. They found that the hydroxylation 

 of )3-carotene is not entirely symmetrical but takes place most readily at 

 the double bonds which are least substituted and sterically most accessible. 

 The oxidation of /3-carotene to give vitamin A aldehyde was also effected 

 with vanadium pentoxide by Meunier et al? 



B. THE AXTIXEROPHTHALMIC VITAMINS OR VITAMINS A 



1. Introduction 

 The early literature in this field has been ably summarized in two ex- 

 cellent monographs,"'^'' and no attempt will be made here to treat the 

 subject exhaustively. 



71 R. F. Hunter, Nature 158, 257 (1946). 



" N. A. Milas and S. Sussman, ./. Am. Chem. Snc. 58, 1302 (1936); 59, 2545 (1937). 

 7' H. R. Rosenberg, Chemistry and Physiology of the Vitamins, pp. 37-95. Inter- 

 science Publishers, New York, 1942. 



