II. CHEMISTRY AND INDUSTRIAL PREPARATION 21 



A activity but acts physiologically to detoxify excessively high stores of 

 vitamin A. It has been isolated from whale (0.8%), shark (0.8%), and 

 dogfish (0.08 %) liver oils. It crystallizes from methanol in colorless elon- 

 gated prisms, m.p. 88 to 90°, .S}^m. (290 m/x) 707. It has a composition 

 corresponding to the formula C4oH58(OH)2 and forms a dinitrobenzoate, 

 m.p. 200°; two diphenyl benzoates, m.p. 125 to 126° (methyl acetate) and 

 149 to 150° (acetone), respectively; and an anthracjuinone carboxylate, 

 m.p. 195 to 197°. It is also optically active, [a\^^jn^ = —1.35 (chloro- 

 form). When its palmitate is distilled in a cyclic molecular still (240 to 

 270°; 0.3 n), 0.67 to 0.75 mole of vitamin A palmitate is foniied per mole 

 of kitol palmitate destroyed. The structure of this interesting carotenoid 

 has not yet been elucidated. 



5. Total Synthesis of Provitamin A Carotenoids 



Almost simultaneously three groups^^"^^ of investigators reported the 

 synthesis of /3-carotene.^^ The synthesis of this and other carotenoids was 

 made possible by the discovery of several new reactions and intermediates 

 in the synthesis of vitamin A.^" One of the intermediates that played an 

 important role in the synthesis of jS-carotene was the octenedione (XXXI), 

 which was first synthesized by Mange^^ in the author's laboratory by the 

 action of dimethyl cadmium on frans-dihydromuconyl chloride. Since then, 

 other methods^^' ^^ have been used for the synthesis of this ketone. The 

 first synthesis^® of jS-carotene made use of this ketone and the Grignard of 

 the acetylenic carbinol (XXX) which was made from /3-ionone and pro- 

 pargyl bromide \'ia the Reformatsky reaction. The tetrol XXXII produced 

 was selectively hydrogenated to give the tetrol XXXIII, which was de- 

 hydrated to jS-carotene with p-toluenesulfonic acid in boiling toluene. The 

 yields of j3-carotene by this method are rather low, owing to the tendency 

 of the tertiary hydroxyl groups in the carbinol XXX as well as that of the 

 same hydroxyl groups in the subsequent intermediates to undergo an 

 anionic rearrangement to produce a tetrol which does not lead to /3-carotene. 

 This objection has been overcome by the second*'^ and third methods,^^ 

 which use the intermediates XXXIV and XXXV, respectively. 



" P. Karrer and C. H. Eugster, Co?npt. rend. 230, 1920 (1950); Helv. Chim. Acta 33, 



1172 (1950). 

 " H. H. Inhoffen, F. Bohlmann, K. Bartram, and H. Pommer, Chem.-Ztg. 74, 285 



(1950); Abhandl. braunschweig. wiss. Ges. 2, 75 (1950). 

 58 N. A. Milas, P. Davis, I. Belie, and D. A. Fles, /. Am. Chcm. Soc. 72, 4844 (1950). 

 5' For a complete review of this subject see H. H. Inhoffen and H. Siemer, Fortschr. 



Chem. org. Naiurstoffe 9, 1 (1952). 

 ^^ See Section II. B of this chapter. 



" E. E. Mange, B. S. Thesis, Massachusetts Institute of Technology, 1948. 

 " R. Ahmad, F. Sondheimer; B. C. L. Weedon, and R. J. Woods, J. Chem. Soc. 1952, 



4089. 



