192 



ASCORBIC ACID 



adding acid thus: 



COOMe 

 I 

 CO 



HO- 



CO— 1 



I 



-c 



HO— C— H 



I 

 H— C— OH 



I 

 HO— C— H 



I 



CH2OH 



XXXI 



NaOMc 



NaO— C 

 I 

 H— CO- 



HO— C— H 

 I 

 CHjOH 



XXXII 



CO— I 



I 

 HO— C 



II 

 HO— C 



I 

 H— CO— ' 



1 

 HO— C— H 



I 



CH2OH 



I 



COOH 

 I 

 CO 



I 



HO— C— H 



I 

 H— C— OH 



I 

 HO— C— H 



I 



CH2OH 



XXXIII 



It is interesting to note that this reaction had been carried out on methyl 

 2-keto-D-gkiconate^* before L-ascorbic acid was synthesized, but the mecha- 

 nism of the reaction was not known and thus the authors were unaware 

 until later^^ that the glucosaccharosonic acid they had made was the first 

 true analog of ascorbic acid, namely, D-araboascorbic acid. 



A less convenient method for synthesizing L-ascorbic acid involving si- 

 multaneous dehydration and isomerization can be brought about by heating 

 2-keto-L-gulonic acid (XXXIII) alone^^- ®^ or in the presence of an acid 

 catalyst, ^^ a reaction accelerated by carrying it out under pressure at an 

 elevated temperature.'^" 



The type of isomerization leading to the formation of an unsaturated 

 five-membered ring system by an internal type of Claisen condensation 

 activated by carbonyl groups is more common than it appears. Thus, it is 

 found in the alkaline conversion of mannosaccharodilactone (XXXIV) into 

 the highly reducing substance 3-desoxy-6-carboxy-D-araboascorbic acid 

 shown to have the formula XXXV^^ and in the formation of a related 

 ascorbic acid-like substance, 3-desoxy-6-carboxy-L-ascorbic acid (XXXVI) 

 from the dilactones (XXXVII), XXXVIII) and lactone esters (XXXIX, 

 XL) of glucosaccharic acid." 



It is of interest to note that all these substances which undergo isomeri- 

 zation to give the ascorbic acid type of ring system possess two carbonyl 

 groups as do those 2-keto esters which yield the true ascorbic acids. A 

 further example of this interesting type of condensation and isomerization 

 is seen in the case of XLI which upon treatment with sodium methoxide 

 furnishes an analog of ascorbic acid which possesses a six-membered ring 



6' M. van Eokelen and P. J. van der Laan, Dutch Pat. 59,582 (1947). 



68 French Pat. 929,751 (1948). 



69 Belgian Pat. 452,811 (1943). 

 '"Dutch Pat. 59,710 (1947). 



" D. nesh)p and F. Smith, J. Chetn. Soc. 1944, 577. 

 " D. Heslop and F. Smith, J. Chem. Soc. 1944, 6.37. 



