Studies toward a synthesis of C3-epimauritine D: construction of the macrocycle

We successfully synthesized a 14-membered cyclic enamide of C3-epimauritine D from the cis-2,3-pyrrolidinediol derivative. Treatment of the pyrrolidinediol with nitrobenzonitrile in an SNAr reaction efficiently installed the desired aryl–alkyl ether linkage on the N-heterocyclic system. Macrocyclization was successfully achieved by the use of TFFH as the peptide coupling reagent in the presence of HOAt.