Synthesis 2014; 46(16): 2179-2190
DOI: 10.1055/s-0033-1339027
paper
© Georg Thieme Verlag Stuttgart · New York

Syntheses of 3-[(Alkylamino)methylene]-6-methylpyridine-2,4(1H,3H)-diones, 3-Substituted 7-Methyl-2H-pyrano[3,2-c]pyridine-2,5(6H)-dione Fluorescence Probes, and Tetrahydro-1H,9H-2,10-dioxa-9-azaanthracen-1-ones

Allan M. Prior
a  Department of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA
,
Medha J. Gunaratna
a  Department of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA
,
Daisuke Kikuchi
a  Department of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA
,
John Desper
a  Department of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA
,
Yunjeong Kim
b  Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-0401, USA
,
Kyeong-Ok Chang
b  Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-0401, USA
,
Izumi Maezawa
c  M.I.N.D. Institute and Department of Pathology, 2825 50th Street, UC Davis Health System, Sacramento, CA 95817, USA   Fax: +1(785)5326666   Email: duy@ksu.edu
,
Lee-Way Jin
c  M.I.N.D. Institute and Department of Pathology, 2825 50th Street, UC Davis Health System, Sacramento, CA 95817, USA   Fax: +1(785)5326666   Email: duy@ksu.edu
,
Duy H. Hua*
a  Department of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA
› Author Affiliations
Further Information

Publication History

Received: 04 March 2014

Accepted after revision: 09 April 2014

Publication Date:
14 May 2014 (eFirst)

Abstract

Various condensation and ring-closing reactions were used for the syntheses of 3-[(alkylamino)methylene]-6-methylpyridine-2,4(1H,3H)-diones, bicyclic pyridinones, and tricyclic morpholinopyrones. For instance, 3-[(dialkylamino)methylene]-6-methylpyridine-2,4(1H,3H)-diones were synthesized from the condensation of dialkylamines and 3-formyl-4-hydroxy-6-methylpyridin-2(1H)-one. 3-Formyl-4-hydroxy-6-methylpyridin-2(1H)-one, derived from 3-formyl-4-hydroxy-6-methylpyridin-2(1H)-one, was used to construct a number of bicyclic pyridinones via a one-pot Knoevenagal and intramolecular lactonization reaction. Tricyclic morpholinopyrones were assembled from a dialkylation reaction involving a dinucleophile, 3-amino-4-hydroxy-6-methyl-2H-pyran-2-one, and a dielectrophile, trans-3,6-dibromocyclohexene. Depending on the reaction conditions, isomers of the tricyclic molecules can be selectively produced, and their chemical structures were unequivocally determined using single-crystal X-ray analyses and 2D COSY spectroscopy. The fluorescently active bicyclic pyridinone compounds show longer absorption (368–430 nm; maximum) and emission wavelengths (450–467 nm) than those of 7-amino-4-methylcoumarin (AMC; λabs,max = 350 nm; λem = 430 nm) suggesting these molecules, such as 3-(2-aminoacetyl)-7-methyl-2H-pyrano[3,2-c]pyridine-2,5(6H)-dione, can be employed as fluorescence activity based probes for tracing biological pathways.

Supporting Information

 
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