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 analo...

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Bibliographic Details
Published in:Organic letters 2006-03, Vol.8 (5), p.919-922
Main Authors: Bock, Victoria D, Perciaccante, Rossana, Jansen, T Paul, Hiemstra, Henk, van Maarseveen, Jan H
Format: Article
Language:English
Subjects:
Catalysis
Copper - chemistry
Cyclization
Molecular Structure
Oligopeptides - chemical synthesis
Oligopeptides - chemistry
Peptides - chemical synthesis
Peptides, Cyclic - chemical synthesis
Peptides, Cyclic - chemistry
Stereoisomerism
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Summary: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.
ISSN:1523-7060
DOI:10.1021/ol053095o