318 RIBOFLAVIN 



T>-Rihose, needed for the riboflavin synthesis described, can be obtained 

 either from natural sources or by synthetic methods. It has been prepared 

 by hydrolysis of yeast nucleic acid.^^ From 2 kg. of yeast, only 1 to 2 g. 

 of pure D-ribose have been obtained via yeast nucleic acid and guanosine. 



The synthetic method starts with glucose, which, via calcium gluconate, 

 is converted to D-ribose through the following steps: D-arabinose, dia- 

 cetyl-arabinal, D-arabinal. The latter, by oxidation with perbenzoic acid, 

 gives a mixture of D-arabinose and D-ribose, with a yield of 10 to 17 %.^^- ^^ 

 The sirupy ribose prepared by this method can be obtained crystallized 

 by conversion to anihne-N-D-ribofuranoside and subsequent hydrolysis 

 (Berger and Lee^O- 



Recently processes have been developed whereby ribose can be prepared 

 directly by electrolytic reduction of ribonolactone. The corresponding acid 

 can be obtained by rearrangement of arabonic acid, which usually is pro- 

 duced by the oxidation of corn sugar in alkaline solution with oxygen or 

 air. By a newer method of the Northern Regional Research Laboratory, 

 calcium arabonate is obtained with 85 % yield by electrolytic oxidation of 

 2-ketogluconate.^'' 



Since the preparation of D-ribose forms a bottleneck in the synthesis of 

 riboflavin, methods have been developed which avoid the use of ribose. 



F. Weygand^^ in 1940 showed that it is possible to use D-arabinose for 

 the synthesis of riboflavin. N-D-Arabinoside of xylidine (I) is transformed 

 by a so-called Amadori isomerization into the isoarabinose derivative II, 

 which under alkaline conditions (possibly favoring the keto form) can be 

 hydrogenated to the intermediate III of the riboflavin synthesis. The 

 yield is about 13 % of the pentose used. 



Later, processes of technical importance were developed which avoid the 

 primary use of pentoses altogether and operate with D-ribonic acid or its 

 lactone. This sugar acid can be obtained by pyridine epimerization of d- 

 arabonic acid, which in its turn is prepared from D-glucose. 



In the procedure of Pfizer and Co.,^^ D-ribonamide is acetylated and the 



" H. Bredereck, Ber. 71, 408 (1938); H. Bredereck, M. Kothnig, and E. Berger, Ber. 



73, 956 (1940). 

 66 M. Gehrke and F. X. Aichner, Ber. 60, 918 (1927) ; W. C. Austin and F. L. Humoller, 



J. Am. Chem. Soc. 56, 1152 (1934); T. Reichstein and M. Steiger, Helv. Chim. Acta 



19, 189, 193 (1936). 

 " C. L. Mehltretter, in "Crops in Peace and War," Yearbook Agr. U. S. Dept. Agr. 



1950-51, 782. 



68 F. Weygand, Ber. 73, 1259, 1264 (1940). Based on a similar principle is the modified 

 synthesis of riboflavin described by V. M. Berezovskil, V. A. Kurdyukova and N. 

 A. Preol)razhanskiI, J. Appl. Chem. (U.S.S.R.) 22, 527, 533 (1949) [C.A. 44,2530 

 (1950)]. A variant of Weygand's method forms the object of a patent of the Miles 



Laboratories, Inc., British Pat. 594,949 (Nov. 24, 1947) [C.A. 42, 2630 (1948)]. 



69 Pfizer and Co., Inc., British Pats. 545,360 (May 21, 1942), 551,401 (P>b. 25, 1943) 

 [C.A. 38, 5845, 2344 (1944)], 585,212 (Feb. 3, 1947) [C.A. 41, 3815 (1947)]. 



