J. S. Nair, K. Rajasekharan
Sep 1, 2004
Citations
0
Influential Citations
1
Citations
Journal
ChemInform
Abstract
Synthesis of four new 3-benzoxa/thiazol-2-ylquinolinemaleimides and their fluorescence properties are described . Among these, the 3-benzothiazol-2-ylquinoline-5-maleimide shows very good enhancement in fluorescence upon thiol addition and thus would serve as a sensitive thiol detection and quantitation reagent. Simi larly, 3-benzoxazol-2-y lquinoline7-maleimide forms a fluorescent conjugate with a model protein BSA th at has good emission properties, both in the native and in the denatured state, as shown by fluorescence spectroscopy and SDS-PAGE ex periments, thus ind ica ting that 3benzoxazol-2-ylquinoline-7-maleimide would be useful as a protein label that gives highly fluores ce nt protein bioconjugates. IPC: Int.Cl 7 C 07 D 215/00 Fluorolabels that are bioconjugatable to proteins find extensive application in various areas of bio sciences.t·2 For these protein labelling reactions, the fluoroprobe should contain a reactive linker group. 3 Maleimide group is a well established linker group which reacts readily with thio l groups in proteins to form an adduct. 4 Quinoline is one of the smaller sized fluorophores and forms highly fluorescent deri vatives .5 This ability has been ex ploited in the detection of amino acids in li ving cells even to a zeptomole level. 5 Apart from it s compact size, quinol in e as a fluorophore has other advantages such as being fluorescent in polar media and favourable solubility properties conferred by the presence of the heteroatom in the aromatic ring . These and other desirable emission properties of aminoquinolines have led to their use in the preparation of se nsitive fluoro genic enzyme substrates. 6 · 7 However, sub stituted aminoquinolines have not been used in the design of fluoroprobes . We now report the synthesis of 5- and 7- amino-3-hetarylquinolines and th eir corresponding 5- and 7-maleimido derivatives as novel thiol-reactive fluoroprobes along with an evaluation of their emission properties and suitability as fluoroprobes. Results and Discussion Maleimides are accessib le in a two step reaction from the respective amines through the intermediate maleamic ac id s. 8 The required 7-amino-3-(2-hetaryl)quinoline in turn could be obtained by Combes quinoline synthesis 9 using substituted malon dialdehydes.1 0 The Vil smeier-Haack formylation of 2methylbenzoxazole 1 and 2-methylbenzothiazole 2 would afford 10 the required 2-(benzoxazol-2-yl) ·· malondialdehyde 3 and 2-(benzothiazol-2-yl)malon ·· dialdehyde 4. We now find that the Combes reaction of 2-(benzoxazol-2-yl)malondialdehyde 3 with m phenylenediamine affords the hitherto unreported 5·· amino-3-benzoxazol-2-ylquinoline S (Scheme I) in addition to the 7-amino-3-benzoxazol-2-ylquinoline 7 as observed by Naik et a/. 10