title: Solid-phase synthesis of bis-heterocyclic compounds from resin-bound orthogonally protected lysine.
abstract: An efficient method for the solid-phase synthesis of bis-heterocyclic compounds from resin-bound orthogonally protected lysine is presented. The initial reaction step involves the exhaustive reduction of resin-bound tetra-amides using borane-THF, followed by cyclization of the resulting tetra-amine with either carbonyldiimidazole, thiocarbonyldiimidazole, or oxalyldiimidazole to generate resin-bound bis-cyclic ureas, bis-cyclic thioureas, and bis-cyclic diketopiperazines, respectively. Cleavage from the solid support using hydrogen fluoride, followed by extraction and lyophilization, yields the desired bis-heterocyclic compounds in excellent yield and high purity.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nefzi
authors.forename: M A
authors.initials: MA
authors.lastname: Giulianotti
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
mesh_terms: D000215:Acylation; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D012116:Resins, Plant
chemical_list: D006571:Heterocyclic Compounds; D012116:Resins, Plant; D008239:Lysine