II. CHEMISTRY 



331 



sihle ill which a lilioHaA'iii antagonist might bring about growth inhibition: 

 (a) by comiH'tition witli tlie prosthetic j^nnip of flavoenzymes; (b) by com- 

 petitively inhibiting the phosphorylation of riboflavin; and (c) by being 

 enzymatically converted to an analog of riboflavin-5-phosphate or flavin 

 adenine diniicleotide, in which form they might competitively inhibit 

 flavoenzj^mes. 



It has been shown that yeast flavokinase, the enzyme which catalyzes 

 the phosphorylation of riboflavin, also phosphorylates D-araboflavin and 

 dichloroflavin to the corresponding nucleotides. The effects of these phos- 

 phorylated riboflavin analogs on flavoenzymes have not yet been studied. 



Isoriboflavin, galactoflavin, and sorboflavin neither are phosphorylated 

 by flavokinase nor do they inhibit the enzymatic phosphorylation of ribo- 

 flavin by flavokinase. This enzymatic process is inhibited by lumiflavin, 

 when present in excess over riboflavin. 



3. NiTROFLAVINS AND BASICALLY SUBSTITUTED ISOALLOXAZINES 



Two 6-nitrofiavins have been synthesized:"^ 



CH2CH2OH CH2CH2N(C2H5)2 



/^^ 



I 



N N 



CO 



NH 



/S/\ ^\ / 



O2N N CO 



6-Nitro-9-(|8-hydroxyethyl)- 

 isoalloxazine 



O2N 



N 



N 



N 



\ 



CO 



II 



/ 

 CO 



NH 



6-Nitro-9-(/3-diethylaminoethyl)- 

 isoalloxazine 



Chemotherapeutic tests with substance I did not show noticeable success. 



The structural similarity between riboflavin and atabrin suggested the 

 synthesis of basically substituted isoalloxazine derivatives as possible anti- 

 malarials. The following types have been prepared.*^- "^-"s 



R"'CH(CH2)„N(C2H5)2 CH2CHOHCH2NR2 



N 



III 



R'- 

 R" 



N 



N 



/\/ v 



\ 



/ 



CO 



CO 

 NH 



H3C 



H3C 



N N 



\/ \q orC2H5 



R = H 



o 



IV 



N CO 



NH 



i'5 H. Hippchen, Bcr. 80, 263 (1947). 



"6 F. E. King and R. M. Achcson, J . Chem. Soc. 1946, 681. 



"' R. R. Adams, C. A. Weisel, and H. S. Mosher, /. Am. Chem. Soc. 68, 883 (1946). 



"8 H. Burkett, J. Am. Chem. Soc. 69, 2555 (1947). 



