Total synthesis of anti-HIV agent chloropeptin I
Total synthesis of anti-HIV agent chloropeptin I
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DOI：
10.1021/ja030249r
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发表时间：
2003-07-30
影响因子：
15
通讯作者：
Hoveyda, AH
中科院分区：
文献类型：
--
作者：
Deng, HB;Jung, JK;Hoveyda, AH
报道了抗HIV药物氯肽素I的收敛非对映选择性和对映选择性全合成。全合成的重要特征包括：（1）使用Ti催化的氰化物加成到亚胺上以制备必需的氨基酸部分，（2）发现MeOH在Cu介导的联芳基醚形成中的积极作用以提供两个大环肽部分之一，和（3）发现了可力丁在非对映选择性Pd介导的交叉-偶联以导致在该医学上重要的分子内有效形成另一大环。这一关键步骤是在四个未保护的酚，其中两个驻留在二氯苯甘氨酸的存在下进行。
A convergent diastereo- and enantioselective total synthesis of anti-HIV agent chloropeptin I is reported. Important features of the total synthesis include: (1) the use of Ti-catalyzed cyanide addition to imines to prepare a requisite amino acid moiety, (2) the discovery of the positive effect of MeOH in the Cu-mediated biaryl ether formation to afford one of the two macrocyclic peptide moieties, and (3) the discovery of the positive influence of collidine in the diastereoselective Pd-mediated cross-coupling to result in efficient formation of another macrocycle within this medicinally important molecule. This key step is performed in the presence of four unprotected phenols, two of which reside on dichlorophenylglycines.