188 



ASCORBIC ACID 



not agree with the formulation of vitamin C as a derivative of a furancar- 

 boxyhc acid.^^ 



The structure (I) assigned above to L-ascorbic acid received full confir- 

 mation from the reactions set out below which have been used for its syn- 

 thesis. 



D. SYNTHESIS OF l-ASCORBIC ACID 



Four principal methods have so far been devised for the synthesis of 

 L-ascorbic acid and its analogs. 



1. Addition of hydrogen cyanide to a glycosone and conversion of the inter- 

 mediate iminoascorhic acid into Jj-ascorbic acid by acid hydrolysis. 



2. Simultaneous lactonization and isomerization of an appropriate 2-keto 

 acid or ester. 



3. Benzoin condensation of sugars with ethyl glyoxylate or ethyl mesoxalate. 



4. Claisen condensation of esters of hydroxy acids. 



Method 1. Addition of Hydrogen Cyanide to a Glycosone and 



Conversion of the Intermediate Iminoascorbic Acid into 



Ascorbic Acid by Acid Hydrolysis 



When an osone such as L-xylosone (XII) is allowed to react with an 

 alkali cyanide in aqueous solution, the usual type of cyanohydrin reaction 

 takes place at Ci. The nitrile (XIII) thus formed ])ut not isolated imme- 

 diately undergoes ring closure to give the 1-imino derivatives^ of L-ascorbic 

 acid (XIV). The latter already contains the highly reactive enediolic sys- 

 tem of ascorbic acid, and upon hydrolysis with dilute acid the desn-ed 

 L-ascorbic acid (I) is readily formed. 



CHO 



I 

 CO 



I 



H— C— OH 



I 

 HO— C— H 

 1 

 CH^OH 



XII 



L-Xylosone 

 (lyxosone) 



HCN 



CN 



I 

 CHOH 



I 



T 



H— C— OH 

 I 

 HO— C— H 

 I 

 CH.OH 



XIII 



NH 



II 



C — 

 I 

 HO— C 



II 

 HO— C 



H— CO- 



HO— C— H 

 I 

 CH.OH 



XIV 



HCl 



CO— 



I 



HO— C 



II 

 HO— C 



H— CO — 



HO— C— H 

 I 

 CH2OH 



I 



Imino-L-ascorbic acid L-Ascorbic acid 



This osone-cyanide method was employed almost simultaneously by two 

 schools^^' s^'Ss for the synthesis of L-ascorbic acid. The major problem in 



"W. N. Haworth, E. L. Hirst, J. K. N. Joues, and F. Smith, /. Cfiem. Soc. 1934, 

 1192. 



