A Novel Methodology for the Synthesis of Fumarates and Maleates

Abstract The stereoselectivity of both the Wittig and the Horner-Wadsworth-Emmons reactions allows for the synthesis of ortho­gonally protected fumarates and maleates, respectively, from α-keto esters. This methodology has been shown to be useful in the synthesis of a derivative of the pH sensitive CIS-aconitic linker, important for prodrug approaches in drug delivery. We have incorporated this linker into a cholesterol-based PEGylated lipid, for its potential use in liposomal drug and gene delivery. The synthesized lipids have also been shown to be pH degradable using HPLC analyses.