[2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
[2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
复制标题
[2 2 2] 以炔丙基卤化物为合作伙伴的环三聚反应：抗肿瘤 Hsp90 抑制剂 AT13387 的正式全合成
作者：
S. Kotha;G. Sreevani
热休克蛋白90（Hsp90）抑制剂在细胞生长中起着重要作用，并显示出抗肿瘤活性。Hsp90抑制剂AT13387（onalb）正在进行治疗难治性胃肠道间质瘤的临床试验。最近，证明了该化合物还表现出对膀胱癌的抑制作用。在这里，我们报告异吲哚啉和异吲哚啉酮为基础的（卤代甲基）苯通过[2 + 2 + 2]环三聚在催化量的Mo（CO）6的存在下。这种策略已经扩展到合成Hsp90抑制剂AT13387的关键前体。
Heat shock protein 90 (Hsp90) inhibitors play a remarkable role in cellular growth, and they were shown to exhibit antitumor activity. The Hsp90 inhibitor AT13387 (onalespib) is under clinical trials for the treatment of refractory gastrointestinal stromal tumors. Recently, it was demonstrated that this compound also exhibits inhibition against bladder cancer. Here, we report isoindoline- and isoindolinone-based (halomethyl)benzenes via a [2 + 2 + 2] cyclotrimerization in the presence of catalytic amounts of Mo(CO)6. This strategy has been extended to synthesize the key precursor of the Hsp90 inhibitor, AT13387.