232 



PYRIDOXINE AND RELATED COMPOUNDS 



« 



autoclaving of pyridoxine with the assay medium or amino acids greatly 

 increased the activity of pyridoxine for the test organism Streptococcus 

 faecalis R. and concluded that the products formed by treating pyridoxine 

 with aminating agents and mild oxidizing agents were, respectively, the 

 amino and aldehyde derivatives of pyridoxine. By deduction it appeared 

 that one of the hydroxymethylene groups in either the 4 or 5 position had 

 been modified. Tests of the compounds synthesized by Harris et al}^-*'^ 

 showed that the compounds were 2-methyl-3-hydroxy-4-aminomethyl- 

 5-hydroxymethylpyridine and 2-methyl-3-hydroxy-4-formyl-5-hydroxy- 

 methylpyridine. 



HO 



CH 



CH2NH2 



CH2OH 



HO 



CHO 



Pyridoxamine 



CH; 



CH2OH 



Pyridoxal 



Pyridoxamine was prepared by aminating either the acylated pyridoxine 

 or, in better yield, by aminating 2-methyl-3-hydroxy-4-methoxymethyl-5- 

 hy droxymethy Ipy ridine . 



HO 



CH 



CH2OCH3 

 ^^^CH20H 



\N^ 



NHa 



120-140° 



HO 

 CH3 



CH2NH2 

 CH2OH 



Owing to the greater reactivity of the methylene group in the 4 position, 

 this reaction was possible. The isomeric 5-aminomethylpyridine was also 

 synthesized. 



Careful oxidation of pyridoxine with potassium permanganate yielded 

 an aldehyde which could be separated from the reaction mixture as its 

 oxime. This was decomposed with nitrous acid and then treated with 

 ethanol and hydrochloric acid to yield a cyclic acetal which easily hydro- 

 lyzed to the desired aldehyde. The proof that the formyl group was in the 

 4 position was accomplished by converting the oxime to the 4-amino com- 

 pound by catalytic reduction. 



39 S. A. Harris, D. Heyl, and K. Folkers, /. Biol. Chem. 154, 315 (1944). 



" S. A. Harris, D. Heyl, and K. Folkers, /. Am. Chem. Soc. 66, 2088 (1944). 



