Syntheses of novel 4-tert-alkyl ether proline-based 16- and 17-membered macrocyclic compounds

Starting from N-Cbz-4-hydroxyproline methyl ester 1, a boron trifluoride-diethyl etherate-catalyzed reaction provided 4-tert-alkyl ether proline 4. Two deprotections and amide bond formations furnished the phenol alcohol 2. The macrocyclization of 2 was accomplished through a Mitsunobu reaction using triphenylphosphine and 1,1'-(azodicarbonyl)dipiperidine (ADDP), to afford novel 16- and 17-membered proline-based macrocyclic compounds of type 3.