722 VII. VITAMINS A 



CH, CH3 CH, CH3 



R-CH: CH-C:CH-CH:CH-C=0 «► R • CH : CH • C : CH • CH : CH • C • CH,C-OC-H, 



, I 



33ZIE / XXXVI OH 



HjC CH3 



\ / 



C 



CHj CHj / 



IMild treotment) 



/\ hhIhhhIh y,0 ^^^ T CH, Q 



H2C C • C : C • C: C • C; C' C: G • C— OC2H5 R. CH.-CH -CrCH-CHrCH-C-CHjC-OCiHi 



^J [I XXXVII xyyv iii 



' \ / \ 

 C CH3 



"' HjC CH3 



\ y Li Al H4 



c ^^^ 



/ \ H H 1 H H H 

 HzC C- C: C- C: C- c: C- C : CHjCHjOH 



I II XXXIX CHj 



H2C C 



\ / \ 

 CH3 



H2 



Sjmthesis of Isomeric Vitamin A Alcohol 



If the hydroxy ester (XXXVI) is treated with suitable catalysts such as 

 acid or iodine, it is dehydrated to form a new compound, which is called 

 "vitamin A3" acid ethyl ester (XXXVIII). The latter compound can be 

 changed to the "vitamin A3" alcohol (XXXIX) by treatment with lithium 

 aluminum hydride. The new vitamin A3 possesses a marked biological 

 potency, approximately 1,000,000 U.S. P. units per gram. It cannot be 

 converted to vitamin Ai by chemical means, and it is not believed that the 

 biopotency can be traced to the presence of vitamin A as an impurity. 

 No differences in the various biological indices of synthetic and of natural 

 vitamin A, respectively, can be noted. ^'^ 



(10) Synthesis of Vitamin A Ethers 



Several of the principal methods for synthesis of vitamin A already 

 described, including those of Milas,^'"^ Isler et al., 208,215 g^j^^j Oroshnik^"^ in- 

 volve the formation of the vitamin A ethers. Additional procedures are 

 listed below. 



a. Milas Synthesis from Glycol Methyl Ether. The glycol methyl 

 ether (XL) can be readily prepared from the glycol (VII, see page 717) 

 used in the preparation of vitamin A by the Milas "A" method, employing 

 1% palladium deposited on calcium carbonate as a catalyst. The glycol 

 methyl ether can be changed to vitamin A methyl ether by any one of 



2" H. M. Wuest and N. Ercoli. Presented before the 115th Meeting of the American 

 Chemical Society in San Francisco, March 27-Apr. 1, 1949, No. 21, pp. 12c, 13c. 



"5 O. Isler, W. Huber, A. Ronco, and M. Kofler, IO46, Jubilee Volume for Emil C. 

 Barrell, p. 31, Hoffmann-LaRoche, Basle, Cited by N. A. Milas, T'/tom//ts and Hormones, 

 5, 20 (1947). 



