8th International Electronic Conference on Synthetic Organic Chemistry. ECSOC-8. 1-30 November 2004. http://www.lugo.usc.es/~qoseijas/ECSOC-8/  

Synthesis of lin-benzo-Ciprofloxacin

Ulrich Jordis, Peter Martinek, Carmen Ortega and Fritz Sauter

Institute of Applied Synthetic Chemistry (IAS)
Vienna University of Technology
Getreidemarkt 9/163-OC, 1060 Vienna, Austria
[email protected]

This publication is dedicated to my post-doctoral mentor Prof. Nelson J. Leonard 

Keywords	quinolones, o-quinodimethane, regioselective nucleophilic aromatic substitution, drug design, dimensional probe
Abstract	The synthesis of a linear extended analog of the important synthetic antibiotic Ciprofloxacin is described.
	Ciprofloxacin1	lin-benzo-Ciprofloxacin
Introduction
Schemes	clickable Scheme1: Structures are molfiles. Scheme 2: conventional
Results
Discussion
References
Electronic publishing note	This poster contains (in Scheme 1) a clickable table with direct links to the experimental. In order to speed up this publication, the original pages of a report or a dissertation were scanned as pdf files. Right-clicking on the structures of Scheme 1 allowes the manipulations of these molfiles as chemical structures.
Software requirements	MDL chime, Adobe Acrobat Reader.

Introduction

Nelson J. Leonard introduced the concept of linear extended analogs of natural products and nucleic acids. Such elongated analogs differ from the natural products only by an increase of 26 Amu of the molecular weight and an increased distance of the "left" and "right" side of the functional groups of the molecule of 2.4 Angstroms, thus acting as dimensional probes of such modified structures for the enzymes or receptors^2,3,4. Lin-benzo analogs of adenine, ATP, NAD, FAD² as well as coffeine, theophyline⁵, guanosine⁶, allopurinol⁷, and lumazin⁸ have been prepared. Recently the influence of expanded-size bases in Watson-Crick pairing⁹ and the development of a genetic system¹⁰ has been investigated.

Earlier we have reported the synthesis of lin-benzo nalidixic acid¹¹. Structural similar compounds to the lin-benzo-ciprofloxacin described lacking the lin-benzo rational have been described^12,13,14. Such compounds could be termed "lin-pyrido-ciprofloxacin":

"lin-pyrido-ciprofloxacin"

Additionally, we have described the synthesis of [1]Benzothieno[3,2-b]pyridone-3-carboxylic acids as potential antibacterials¹⁵ that could be termed "lin-thieno-quinolones".

The formal insertion of a benzene ring into ciprofloxacin (fig.1)

Fig.1: The lin-benzo rational of drug design: formal insertion of a benzene ring into Ciprofloxacin¹

leads to retro-synthetic approach with a tetra-substituted naphthalene as key intermediate:

With such an intermediate in hand, the remaining uncertainties include the regioselective nucleophilic aromatic substitution. In order to allow a structural proof of this we also prepared the bromo-analog of lin-benzo-ciprofloxacin (19b).

Results

Our synthetic efforts are summarized in

scheme 1 and

scheme 2

A detailed discussion will be presented with the full version of this paper.

Discussion

We have prepared lin-benzo-ciprafloxacin. The antibacterial activity will be reported elsewhere.

References