SYNTHESIS OF THE GLUCURONIC-ACID CONJUGATE OF METHYLAZOXYMETHANOL

The glucuronic acid conjugate of methylazoxymethanol [a possible carcinogenic metabolite] was synthesized by oxidizing the primary alcohol of the glucose moiety of cycasin (methylazoxymethanol-.beta.-D-glycopyranoside) to a carboxylic acid. The oxidation was carried out by bubbling oxygen gas through a cycasin solution in the presence of a platinum-on-carbon catalyst. A band at 1715 cm-1, not present in the cycasin IR spectrum, appeared in the spectrum of the oxidized cycasin product, establishing the presence of a carboxylic acid group. The oxidation product is methylazoxymethanol-.beta.-D-glucosiduronic acid because, when hydrolyzed with Escherichia coli .beta.-glucuronidase, it produced methylazoxymethanol and glucuronic acid and also indicated retention of the .beta.-linkage of cycasin. Varying quantities of the synthesized methylazoxymethanol-glucosiduronic acid, injected into Wistar rats of both sexes and of varying weights, were not acutely toxic. The compound was mutagenic to Salmonella typhimurium when preincubated with E. coli .beta.-glucuronidase, but not when preincubated with bovine liver glucuronidase.