Synthesis of N-alkoxybenzoylmorpholinols as possible metabolites of trithiozine.

The synthesis of some possible metabolites of trithiozine, a new antisecretory-antiulcer drug, is reported. The metabolite 4-(3,4,5-trimethoxybenzoyl)-2-morpholinol (III a) was prepared by oxidative cyclization of the corresponding diethanolamine derivative (II a). Similarly, 4-syringoyl-2-morpholinol (III c) was also obtained and both were converted into the methyl ethers (IV a, c), respectively. The same oxidative approach, starting from the alcohol (VII), afforded the isomeric 4-(3,4,5-trimethoxybenzoyl)-3-morpholinol (IX a) in low yields; therefore a four step process, involving the acid hydrolysis of the acetal intermediate (XII a) was preferred. In the course of the synthetic work 4-(3,4,5-trimethoxybenzoyl)-3-morpholone (V), a potential metabolite itself, was also prepared.