Pyrrolizidine alkaloid analogues. Part 2. Further hydroxymethyl-1-methyl-3-pyrrolines (synthanecines), and the preparation and esterification of some hydroxymethylpyrroles

Abstract

The preparation is described of 2-(2-hydroxyethyl)-3-hydroxymethyl-1-methyl-3-pyrroline (synthanecine D)(11) and 3-hydroxymethyl-1,2-dimethyl-3-pyrroline (synthanecine E)(21), esters of which behave as analogues of pyrrolizidine alkaloids which can be metabolically dehydrogenated in animals to pyrrole derivatives which are monofunctional alkylating agents. The corresponding pyrroles (15) and (23) and several other new hydroxymethylpyrroles have been prepared and the esterification of some of these is described. The electrophilic reactivities of a number of hydroxymethyl-pyrrole and -indole derivatives towards 4-p-nitrobenzylpyridine are compared, and the base-catalysed conversion of diethyl (N-ethoxycarbonylmethyl)-3-methylaminoglutarate (5) to 3-ethoxycarbonyl-4-hydroxy-1-methylpyrrole (45) is described.