阴离子诱导的区域和化学选择性酰化反应及其在抗癌药物合成中的应用。

An anion-induced regio- and chemoselective acylation and its application to the synthesis of an anticancer agent.

作者信息

Poirier M, Chen F, Bernard C, Wong Y S, Wu G G

机构信息

Chemical Process Research and Development, Schering-Plough Research Institute, 1011 Morris Avenue, Union, New Jersey 07083, USA.

出版信息

Org Lett. 2001 Nov 15;3(23):3795-8. doi: 10.1021/ol016809d.

DOI:10.1021/ol016809d

PMID:11700141

Abstract

[reaction--see text] An efficient Grignard- and organolithium-induced regio- and chemoselective anionic acylation is reported. A number of tricyclic ketones are prepared in good to excellent yields via this method. This method is complementary to the Frieldel-Crafts acylation for electron-deficient substrates. A novel anisole-based Grignard reagent was developed to effect the cyclization of sterically hindered substrates. This novel reagent has been successfully applied to the synthesis of Sch 66336, a candidate for oncologic treatment.

摘要

[反应——见正文] 据报道，一种高效的格氏试剂和有机锂试剂引发的区域和化学选择性阴离子酰化反应。通过该方法可制备多种三环酮，产率良好至优异。该方法对于缺电子底物而言是傅克酰化反应的补充。开发了一种新型的基于苯甲醚的格氏试剂，以实现位阻较大底物的环化反应。这种新型试剂已成功应用于合成抗肿瘤治疗候选药物Sch 66336。