Solid-phase synthesis of bis-heterocyclic compounds from resin-bound orthogonally protected lysine.
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.
Nefzi
A
A
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, USA.
Giulianotti
M A
MA
Houghten
R A
RA
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
D006571:Heterocyclic Compounds; D012116:Resins, Plant; D008239:Lysine