Synthesis development of an aminomethylcycline antibiotic via an electronically tuned acyliminium Friedel-Crafts reaction

被引：10

作者：

Chung, John Y. L. ^{[1
]}

Hartner, Frederick W. ^{[1
]}

Cvetovich, Raymond J. ^{[1
]}

机构：

[1] Merck Res Labs, Proc Res, Rahway, NJ 07065 USA

来源：

TETRAHEDRON LETTERS | 2008年 / 49卷 / 42期

关键词：

minocycline; aminomethylcycline; acyliminium; Friedel-Crafts; back-epimerization;

D O I：

10.1016/j.tetlet.2008.08.011

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

With the goal of improving the synthetic efficiency, the development of a convergent synthesis of a minocycline derivative PTK0796 via an intermolecular acyliminium Friedel-Crafts reaction (Tscherniac-Einhorn reaction) is described. The entire C9 neopentylaminomethyl side chain was installed in one step using an electronically optimized chloromethylacyliminium precursor in 83% yield. Deprotection and re-equilibration to the C4 alpha-epimer in the presence of CaCl2 and ethanolamine or NaOH afforded the target aminomethylcycline antibiotic. The corresponding crystalline tosylate salt was found to exhibit improved solid state stability. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6095 / 6100

页数：6

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