Studies on the Chemical Synthesis of Potential Antimetabolites. XXV. Synthesis of (±)-Isowillardiine by Application of a Four-Component Condensation involving 2-Picolylamine 1-Oxide and 2-Picolyl Isocyanide 1-Oxide

Abstract

3-(2-Amino-2-carboxyethyl)uracil (racemic isowillardiine) was synthesized by the use of a four-component (aldehyde, amine, isocyanide, and carboxylic acid) condensation as the key reaction. Thus, 1-(2-picolyl 1-oxide)-3-(formylmethyl) uracil was allowed to react with 2-picolylamine 1-oxide and cyclohexyl isocyanide or 2-picolyl isocyanide 1-oxide in the presence of acetic acid in methanol to afford the corresponding condensation product, which after deblocking, gave (±)-isowillardiine in fair yield.