5-BIS(HYDROXYMETHYL)-3-METHYL-2-OXOMORPHOLIN-3-YL] (BHM-3 DIMER) - A LOW TOXICITY, WATER-SOLUBLE, ONE-ELECTRON REDUCING AGENT

5-bis(hydroxymethyl)-3-methyl-2-oxomorpholin-3-yl] (BHM-3 dimer) was s ynthesized by condensing tris(hydroxymethyl)aminomethane with ethyl py ruvate to form -5,5-bis-(hydroxymethyl)-3-methyl-1,4-oxazin-2-one (1) followed by photoreduction in 2-propanol. BHM-3 dimer exists in equili brium with ,5-bis(hydroxymethyl)-3-methyl-2-oxomorpholin-3-yl (BHM-3) in solution; the rate constant for BHM-3 formation from dimers varies with solvent increasing from 5.3 x 10(-6) s-1 in acetonitrile to 1.5 x 10(-3) s-1 in water at 25-degrees-C. BHM-3 reacts as a one-electron r educing agent, and the reduction potential for BHM-3 dimer is estimate d at -0.54 V vs NHE from the position of equilibrium for the reduction of the viologen, propyldiquat, to its radical cation. BHM-3 dimer has an octanol/water partition coefficient of 0.054 and shows low mouse t oxicity even upon intravenous administration. Intravenously administer ed BHM-3 dimer projects mice from an immediated subsequent lethal inje ction of the antitumor drug adriamycin. The properties of BHM-3 dimer are compared with those of other 2-oxomorpholin-3-yl dimers.