Ring-closing metathesis in the synthesis of biologically active peptidomimetics of apicidin A
Ring-closing metathesis in the synthesis of biologically active peptidomimetics of apicidin A
复制标题
DOI：
10.1002/adsc.200600421
复制
发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Barrett, Anthony G. M.
中科院分区：
文献类型：
--
作者：
Deshmukh, Prashant H.;Schulz-Fademrecht, Carsten;Barrett, Anthony G. M.
报道了新型16元大环肽模拟物的合成，其采用迭代肽偶联，然后进行高产率的闭环复分解（RCM）作为关键环化步骤。目标大环化合物包括含有（2S）-氨基-8-氧代癸酸（Aoda）残基作为apicidin A（一种已知的有效组蛋白脱乙酰酶（HDAC）抑制剂）类似物的实例。这些显示出作为HDAC抑制剂的适度水平的生物活性。
Syntheses of novel 16-membered macrocyclic peptidomimetics are reported, which employ iterative peptide coupling followed by high yielding ring-closing metathesis (RCM) as the key cyclization step. The target macrocyclic compounds include examples containing a (2S)-amino-8-oxodecanoic acid (Aoda) residue as analogues of apicidin A, a known potent histone deacetylase (HDAC) inhibitor. These showed modest levels of biological activity as HDAC inhibitors.