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.
Chen
Kevin X
KX
Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3-3545, Kenilworth, NJ 07033, USA. Kevin.chen@spcorp.com
Njoroge
F George
FG
Vibulbhan
Bancha
B
Buevich
Alexei
A
Chan
Tze-Ming
TM
Girijavallabhan
Viyyoor
V
D020650:Combinatorial Chemistry Techniques / Q000379:methods; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006909:Hydroxyproline / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D006571:Heterocyclic Compounds; C462739:N-Cbz-4-hydroxyproline methyl ester; D011392:Proline; D006909:Hydroxyproline