Solid-phase synthesis of amine-bridged cyclic enkephalin analogues via on-resin cyclization utilizing the Fukuyama-Mitsunobu reaction.
An efficient solid-phase synthetic route is described for the preparation of 13-membered amine-bridged cyclic enkephalin analogues (ABEs) 1a and 1c-1j (Figure 1) resulting from a sulfonamide-containing peptide whose backbone is bound to a resin. The Fukuyama-Mitsunobu reaction of the 2-nitrobenzenesulfonyl-protected amine bound to the solid support with protected aminoethanol in the presence of triphenylphosphine and diisopropyl azodicarboxylate (DIAD) is utilized to prepare a resin-bound sulfonamide-protected secondary amine. After peptide cyclization, this protected amine functionality becomes the "amine bridge" of the target molecule. In addition, the reagent DIAD was found to be a superior reagent compared to diethyl azodicarboxylate (DEAD) in the solid-phase Fukuyama-Mitsunobu reaction.
Rew
Yosup
Y
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093-0343, USA.
Goodman
Murray
M
D000588:Amines / Q000737:chemistry*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004745:Enkephalins / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D012117:Resins, Synthetic / Q000737:chemistry; D013329:Structure-Activity Relationship
D000588:Amines; D001952:Bridged-Ring Compounds; D004745:Enkephalins; D007202:Indicators and Reagents; D010456:Peptides, Cyclic; D012117:Resins, Synthetic