[Molecules: 2] [Related articles/posters: 010 036 074 005 102 ]

[1]Benzothieno[3,2-b]pyridone-3-carboxylic acids as potential antibacterials

Fritz Sauter, Ulrich Jordis and Peter Martinek

Vienna University of Technology, Inst. Organic Chemistry, Getreidemarkt 9/154, A-1060 Vienna, Austria

Keywords	Quinolones / Gyrase Inhibitors / lin-benzo / Grohe quinolone synthesis / electronic publishing /
ECHET96 Electronic Publishing Note	This poster consists of a clickable table of the reaction scheme. Clicking on the structures of the scheme leads to a link of a scanned image of the corresponding experimental part of the thesis of Peter Martinek. Details of the process and software used to produce this paper are described here
Abstract	The synthesis of the title compounds A focusing on the regioselective nucleophilic aromatic substitution of 1-substituted 7,8-difluoro-1,4-dihydro-4-oxo- [1]benzothieno[3,2-b]pyridine-3-carboxylic anhydrides with difluoroboric acid (B) as potential antibacterials is described:
	See also the accompanying poster "Who can model new quinolone-type heterocycles as potential antibacterials? Synthesis of thieno[2',3':4,5]thieno[3,2-b]pyridone-3-carboxylic acids"

Introduction

Quinolones constitute the only important class of broad spectrum antibacterials that are totally synthetic and have so far no structural precedence in nature. As quinolones are susceptable to often surprising activity changes with minor modification of their structure we felt, that the formal insertion of an thiophene ring into the bicyclic aromatic motiv of quinolones might lead to active gyrase inhibitors. In analogy to Leonard's lin-benzo-purines such compounds could be seen as "lin-thieno-quinolones", compound 7b even as "lin-iso-thieno-ciprofloxacin".

Synthesis

The target compounds were prepared following Grohe`s quinolone synthesis [1] via substituted 3-chloro-[1]benzothieno-2-carboxylic acid chlorides. The reaction of aromatic acrylic acids with thionyl chloride and catalytic amounts of pyridine - the mechanism of this reaction was studied by Krubsack [2] - constitutes a simple and generalizable method for the preparation of 3-chloro-benzo[b]thiophene-2-carboxylic acid chlorides. This reaction was optimized most importantly by slow addition of the thionyl chloride that led to a higher reaction temperature and reliable conversion. The following table summarizes the synthesis path:

Scheme 1

Experimental

References

Bayer AG DOS 2808 070 (1978) (Chem. Abstr.1980, 92, 41916w.
T. Higa and A. J. Krubsack, J. Org. Chem., 1975, 40, 3037.