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; Medha J. Gunaratna; Daisuke Kikuchi; John Desper; Yunjeong Kim; Kyeong-Ok Chang; Izumi Maezawa; Lee-Way Jin; Duy H. Hua

doi:10.1055/s-0033-1339027

Synthesis, Table of Contents

Synthesis 2014; 46(16): 2179-2190
DOI: 10.1055/s-0033-1339027

paper

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

^aDepartment of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA

,

Medha J. Gunaratna

^aDepartment of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA

,

Daisuke Kikuchi

^aDepartment of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA

,

John Desper

^aDepartment of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA

,

Yunjeong Kim

^bDepartment of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-0401, USA

,

Kyeong-Ok Chang

^bDepartment of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-0401, USA

,

Izumi Maezawa

^cM.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

^cM.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*

^aDepartment of Chemistry, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506-0401, USA

› Author Affiliations

Abstract

All articles of this category

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; λ_abs,max = 350 nm; λ_em = 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.

Key words

dialkylation - fluorescence probes - heterocycles - 3-substituted 7-methyl-2H-pyrano[3,2-c]pyridine-2,5(6H)-diones - tetrahydro-1H,9H-2,10-dioxa-9-azaanthracen-1-ones

Full Text

References

References
1 Pokhrel L, Maezawa I, Nguyen TD. T, Chang K.-O, Jin L.-W, Hua DH. J. Med. Chem. 2012; 55: 8969
2 Pokhrel L, Kim Y, Nguyen TD, Prior AM, Lu J, Chang KO, Hua DH. Bioorg. Med. Chem. Lett. 2012; 22: 3480
3 Schmidt HW, Junek H. Monatsh. Chem. 1978; 109: 1075
4 Stoyanov EV, Ivanov IC. Synth. Commun. 1998; 28: 1755
5 El-Essawy F, Khattab AF, Zahran MA, Gomaa SH. Synth. Commun. 2007; 37: 3225
6 Feau C, Klein E, Kerth P, Lebeau L. Synth. Commun. 2010; 40: 3033
7 Moffett RB. J. Org. Chem. 1970; 35: 3596
8 Heal WP, Tam Dang TH, Tate EW. Chem. Soc. Rev. 2011; 40: 246
9 Speers AE, Adam GC, Cravatt BF. J. Am. Chem. Soc. 2003; 125: 4686
10 Fan W, Li W, Ma X, Tao X, Li X, Yao Y, Xie X, Zhang Z. J. Org. Chem. 2011; 76: 9444
11 Hua DH, Huang XD, Tamura M, Chen Y, Woltkamp M, Jin LW, Perchellet EM, Perchellet JP, Chiang PK, Namatame I, Tomoda H. Tetrahedron 2003; 59: 4795
12 Han X, Khedekar RN, Masnovi J, Baker RJ. J. Org. Chem. 1999; 64: 5245
13 Radl S, Houskova V, Zikan V. Cesko-Slov. Farm. 1989; 38: 219
14 Dauben HJ. Jr, McCoy LL. J. Am. Chem. Soc. 1959; 81: 4863
15 Hrdlovic P, Donovalova J, Stankovicova H, Gaplovsky A. Molecules 2010; 15: 8915
16 Brouwer AM. Pure Appl. Chem. 2011; 83: 2213
17 Li X, Patron A, Tachdjian C, Xu H, Li Q, Pronin A, Servant G, Zhang L, Brady T, Darmohusodo V, Arellano M, Selchau V, Ching BW, Karanewsky DS, Brust P, Ling J, Zhao W, Priest C. WO 2009,025,793, 2009
18 Shahid A, Raza MA, Rehman S.-U. Afr. J. Biotechnol. 2009; 8: 5116

Supplementary Material

Supporting Information