Synthesis of macrocyclic peptide analogues of proteasome inhibitor TMC-95A
Synthesis of macrocyclic peptide analogues of proteasome inhibitor TMC-95A
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DOI：
10.1021/jo035256c
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发表时间：
2003-12-12
影响因子：
3.6
通讯作者：
Vidal, J
中科院分区：
文献类型：
--
作者：
Berthelot, A;Piguel, S;Vidal, J
本文报道了作为蛋白酶体抑制剂的TMC-95 A的三个限制性大环肽类似物1的合成。关键步骤涉及Ni（0）介导的带有卤代芳香族侧链的三肽2的大环化，以形成联芳基连接。此外，使用甘氨酸二苯甲酮亚胺的Corey-O 'Donnell烷基化以良好的总产率实现了L-7-溴色氨酸甲酯3的对映选择性制备，在数克规模上具有非常高的ee（>85%）。
The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as potential proteasome inhibitors is described. The key step involves a Ni(0)-mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side chains for the formation of the biaryl junction. In addition, an enantioselective preparation of L-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell alkylation of the glycine benzophenone imine was achieved in good overall yield with very high ee (>85%) on a multigram scale.