Synthesis of FunctionalizedPyroglutamic Acids, Part 2: The Stereoselective Condensation ofMultifunctional Groups with Chiral Levulinic Acids

A general procedure to access 3-hydroxy-4-oxopentanoic acid derivatives is described. A key feature is an aldol reaction with an enal as a masked pyruvic aldehyde. Chiral levulinic acid derivatives are provided as precursors for isocyanide-mediated condensation of multifunctional groups, which affords functionalized pyroglutamic acids. The stereoselectivity in the Ugi 4C-3C reaction with the chiral keto acids is examined.