Mechanism and synthesis of pharmacologically active quinolones from Morita-Baylis-Hillman adducts

被引：41
作者：
Amarante, Giovanni W. [2 ]
Benassi, Mario [1 ]
Pascoal, Robert N. [2 ]
Eberlin, Marcos N. [1 ]
Coelho, Fernando [2 ]
机构：
[1] Univ Estadual Campinas, ThoMSon Mass Spectrometry Lab, Inst Chem, BR-13083970 Campinas, SP, Brazil
[2] Univ Estadual Campinas, Lab Nat Prod & Drug Synth, Inst Chem, BR-13083970 Campinas, SP, Brazil
来源：
TETRAHEDRON | 2010年 / 66卷 / 24期
基金：
巴西圣保罗研究基金会;
关键词：
Morita-Baylis-Hillman; 4-Quinolones; N-Oxides; Antibiotics; Alzheimer disease; ELECTROSPRAY-IONIZATION MASS; STEREOSELECTIVE-SYNTHESIS; HECK REACTION; N-OXIDES; CARBOXYLIC-ACID; DERIVATIVES; DNA; NORFLOXACIN; CYCLIZATION; REACTIVITY;
D O I：
10.1016/j.tet.2010.04.018
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
The synthesis of quinolones from Morita-Baylis-Hillman (MBH) adducts is reported. The quinolone skeleton is formed via a TFA-mediated cyclization of the MBH adduct, and a mechanism study using ESI (+)-MS(/MS) has indicated the role played by TFA in this key reaction step. The total syntheses of Norfloxacin and a benzyl quinolone carboxylic acid (BQCA) derivative are described. Norfloxacin is a fluoroquinolonic antibacterial drug whereas BQCA is M-1 receptor positive allosteric modulator and seem to provide access to new potential drugs for Alzheimer disease, pain, and sleep disorders. The syntheses of these two important quinolones exemplify the versatility and potentiality of the approach. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4370 / 4376
页数：7
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