Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction.
Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction.
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DOI：
10.1039/c4sc02547d
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发表时间：
2015-01-01
期刊：
影响因子：
8.4
通讯作者：
Spring DR
中科院分区：
文献类型：
--
作者：
Alza E;Laraia L;Ibbeson BM;Collins S;Galloway WRJD;Stokes JE;Venkitaraman AR;Spring DR
报道了一种以前未描述过的富含sp 3的6-5-5-6四环骨架的合成，其使用钯催化的多米诺Heck-Suzuki反应。报道了一种以前未描述过的富含sp 3的6-5-5-6四环骨架的合成，其使用钯催化的多米诺Heck-Suzuki反应。该反应产率高，对多米诺过程的选择性优于直接Suzuki反应，并且耐受各种硼酸。新的支架也可以通过多米诺Heck-Stille和自由基环化来获得。发现基于该支架的化合物在人癌细胞系中是有效的抗有丝分裂剂。详细的表型分析表明，这些化合物影响染色体的聚集，导致有丝分裂停滞和凋亡细胞死亡。因此，已经鉴定了不破坏微管蛋白网络的新型结构类别的抗有丝分裂剂。
The synthesis of a previously undescribed sp3-rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck–Suzuki reaction is reported. The synthesis of a previously undescribed sp3-rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck–Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed via domino Heck–Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.
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