Bock Victoria D, Perciaccante Rossana, Jansen T Paul, Hiemstra Henk, van Maarseveen Jan H
Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands.
Org Lett. 2006 Mar 2;8(5):919-22. doi: 10.1021/ol053095o.
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.
尽管有大量用于环化小肽的技术，但由于导致环状产物的过渡态不利，一种有效的酪氨酸酶抑制剂环[（L）-脯氨酸-（L）-酪氨酸-（L）-脯氨酸-（L）-缬氨酸]的合成仍然难以实现。在此，我们报道了其唑类似物环[（L）-脯氨酸-（L）-缬氨酸-ψ（三唑）-（L）-脯氨酸-（L）-酪氨酸]的成功合成。在室温下通过肽键形成进行环化尝试未能得到所需产物，但在110℃下铜（I）催化的炔烃-叠氮化物偶联反应以70%的产率得到了三唑四肽，证明了“点击”化学的实用性。
