Document Report Card

ID: ALA3243952

Journal: J Med Chem

Title: Antagonists of vitamin B6. Simultaneous and stepwise modification of the 2 and 4 positions.

Authors: Korytnyk W, Potti PG.

Abstract: Methods for the simultaneous and stepwise modification of the 2 and 4 positions of vitamin B6 have been devloped and have been applied to the synthesis of several analogues of this vitamin. 3,alpha5-O-Dibenzylpyridoxol was converted to its N-oxide and was rearranged to an alpha2-hydroxy derivative with (CF3CO)2O. The 2,4-bis(hydroxymethyl) intermediate was oxidized (MnO2) to the 2,4-dialdehyde, which was converted by a Wittig reaction with triphenylmethylphosphorane to the 2,4-divinyl derivative. Removal of the benzyl groups with acid gave the 2,4-divinylpyridioxol analogue, which was phosphorylated in the 5' position to give the cofactor analogue. The 2-CH3 in the known vitamin B6 antagonists, 4-deoxypyridoxol and 4-vinylpyridoxal, was similarly modified to CH2OH, CHO, and CH = CH2. Modifications of the 2 position in the vitamin B6 antagonists are expected to be associated with changes in selectivity for enzymes in various tissues without a concomitant loss of biological activity, because of the well-established bulk tolerance in this position. Active analogues are expected to undergo, in vivo 5-phosphorylation, which is probably a prerequisite for their antagonist activity. Some of the compounds (e.g., the 2,4-divinyl analogue) have substantial growth-inhibitory activity for cultured mouse mammary adenocarcinoma. In contrast to that of the parent compounds, this activity was only partially reversed by pyridoxal.

CiteXplore: 556772

DOI: 10.1021/jm00211a001