Click chemistry as a route to cyclic tetrapeptide analogues: synthesis of cyclo-[Pro-Val-psi(triazole)-Pro-Tyr].
Despite the plethora of techniques to cyclize small peptides, a synthesis of cyclo-[(L)Pro-(L)Tyr-(L)Pro-(L)Val], a potent tyrosinase inhibitor, remains elusive because of the unfavorable transition state leading to the cyclic product. Herein, we report the successful synthesis of its triazole analogue, cyclo-[(L)Pro-(L)Val-psi(triazole)-(L)Pro-(L)Tyr]. Attempted cyclization via peptide bond formation at room temperature fails to provide the desired product, but Cu(I)-catalyzed alkyne-azide coupling at 110 degrees C affords the triazole tetrapeptide in 70% yield, demonstrating the utility of "click" chemistry.
Bock
Victoria D
VD
Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands.
Perciaccante
Rossana
R
Jansen
T Paul
TP
Hiemstra
Henk
H
van Maarseveen
Jan H
JH
D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; C514785:cyclo-(Pro-Val-psi(triazole)-Pro-Tyr); D003300:Copper