title: Convenient Preparation of 4-Formyl-3,5-dimethoxyphenol and Its Incorporation into Linkers and Resins for Solid-Phase Synthesis.
abstract: 4-Formyl-3,5-dimethoxyphenol (1) is a key synthetic intermediate used to prepare the BAL family (backbone amide linker) of acid-labile linkers and resins. The utility of these linkers and resins for solid-phase synthesis of both peptides and non-peptides has been amply demonstrated. In this article we report a simple and scalable procedure for preparation of isomerically pure 4-formyl-3,5-dimethoxyphenol (1) and its subsequent incorporation into a representative BAL linker and functionalized resin: 4-(4-formyl-3,5-dimethoxyphenoxy)butanoic acid and 4-formyl-3,5-dimethoxyphenoxy-polystyrene, respectively. The procedures are reproducible, are readily scalable, and require no chromatography.
authors.affiliation: Medicinal Chemistry Department, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, Pennsylvania 19406-2711.
authors.initials: J
authors.lastname: Jin
authors.initials: TL
authors.lastname: Graybill
authors.initials: MA
authors.lastname: Wang
authors.initials: LD
authors.lastname: Davis
authors.initials: ML
authors.lastname: Moore