Synthesis and biological properties of 4-amino- and 4-bromo-4-norpyridoxol. New approaches for the modification of the 4 position of vitamin B6.
4-Amino-4-norpyridoxol, a new key intermediate for the modification of the 4 position of vitamin B6, has been obtained by an unusual photochemical rearrangement of pyridoxal oxime. It has also been synthesized starting from 3,-alpha5-O-dibenzylpyridoxal, which was converted to 3,alpha5-O-dibenzylpyridoxamide. The latter, on Hoffman reaction, gave the desired 3,5-blocked 4-amino derivative. Several derivatives of this analogue have been prepared, and its existence in the amino tautomeric form has been established by NMR spectroscopy. A modified Sandmeyer reaction on 4-amino-4-norpyridoxol gave the 4-bromo analogue, which was found to be moderately active as an inhibitor of mouse mammary adenocarcinoma cells grown in cell culture, whereas the 4-amino analogue was not active at 10(-4)M. Other analogues containing electron-withdrawing and electron-donating substituents in the 4 position of pyridoxine were also tested.
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D003864:Depression, Chemical; D005260:Female; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D011736:Pyridoxine