202 ASCORBIC ACID 



In the case of rats, for which L-ascorbic acid is not a vitamin, it appears 

 that when they are stimulated into producing excessive amounts of l- 

 ascorbic acid, by administration of chloretone, they do so at the expense 

 of gkicose; this has l;)een estabUshed by feeding the rats D-gkicose-1-C^'* 

 and showing that the excreted L-ascorbic acid contains radioactive car- 

 bon mainly at Ce-"^^ « 



F. DERIVATIVES OF l-ASCORBIC ACID 



The physiological activity and the novel dieneolic system of L-ascorbic 

 acid have led to much experimentation by workers in the fields of pure 

 chemistry and the applied biological sciences. From the various derivatives 

 referred to below it will be apparent that the hydroxyl groups located at 

 C5 and Ce behave in the normal manner whereas the other two hydroxyl 

 groups located at C2 and C3, the CO group of the five-membered lactone 

 ring, and the double bond display what at one time were thought to be 

 very unexpected properties. Thus, the acidity is due not to the lactone 

 ring but to the hydroxyl groups at C2 and C3, the one at C3 being much 

 more acidic (pK 4.1) than that at C2 (pK 11.6),"^ a deduction previously 

 made from the methylation experiments with diazomethane.^^- " Hence, 

 in the presence of alkali the lactone ring does not open but instead a proton 

 is expelled from the OH at C3; this behavior, with the subsequent trans- 

 formation of the ionized ring system into a state of resonance, no doubt 

 explains the high rotation of the sodium salt and the movement of the 

 absorption band towards longer wavelengths.^- Similarly, it is found that 

 the double bond is also rather vniique inasmuch as reagents such as chlo- 

 rine and bromine, which normally add to a double bond, bring about satura- 

 tion of the bond by oxidation to dehydroascorbic acid. It is also interesting 

 to note that, after the acidity of the hydroxy groups at C2 and C3 has been 

 neutralized by methylation with diazomethane to give the dimethyl ether 

 (IX) of ascorbic acid, the lactone ring can be opened but then only by the 

 concomitant saturation of the double bond by ring closure between Ce and 

 C3 (see later). 



1. Dehydroascorbic Acid 



From the biochemical point of view, this is perhaps one of the more 

 important derivatives of L-ascorbic acid because it still retains the same 

 antiscorbutic activity as the vitamin itself.^* Although easily produced in 

 solution, it is also sensitive to oxidation and until relatively recently it was 

 not possible to isolate it in good jdeld in the crystalline state. 1-" It may be 



"8a H. H. Horowitz, A. P. Doerschuk, and C. G. King, /. Biol. Chem. 199, 193 (1952). 

 lis T. W. Birch and L. J. Harris, Biochem. J. 27, 595 (1933). 

 "0 J. Kenyon and N. Munro, J. Chem. Soc. 1948, 158. 



