On Pyridopyrazinol Chemistry: Synthesis of Chemiluminescent Substances

Glwadys Gagnot; Pierre Legrand; Amira Tadros; Fatima Ezzahra Hibti; Alessia Quatela; Yves L. Janin

doi:10.1055/a-1396-8607

Synthesis, Table of Contents

Synthesis 2021; 53(14): 2477-2484
DOI: 10.1055/a-1396-8607

paper

On Pyridopyrazinol Chemistry: Synthesis of Chemiluminescent Substances

Glwadys Gagnot

^aUnité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France

^bUnité Mixte de Recherche 3523, Centre National de la Recherche Scientifique, 28 rue du Dr Roux, 75724 Paris Cedex 15, France

^cUniversité de Paris, 12 rue de l’école de Médecine, 75006 Paris, France

,

Pierre Legrand

^dSynchrotron Soleil, L’Orme des Merisiers, Saint-Aubin, Gif-sur-Yvette, France

,

Amira Tadros

^aUnité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France

^bUnité Mixte de Recherche 3523, Centre National de la Recherche Scientifique, 28 rue du Dr Roux, 75724 Paris Cedex 15, France

,

Fatima Ezzahra Hibti

^eHORIBA FRANCE SAS, 14 Boulevard Thomas Gobert, Passage Jobin Yvon CS45002, 91120 Palaiseau, France

,

Alessia Quatela

^eHORIBA FRANCE SAS, 14 Boulevard Thomas Gobert, Passage Jobin Yvon CS45002, 91120 Palaiseau, France

,

Yves L. Janin ∗

^aUnité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France

^bUnité Mixte de Recherche 3523, Centre National de la Recherche Scientifique, 28 rue du Dr Roux, 75724 Paris Cedex 15, France

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Abstract

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Abstract

Our work on new chemiluminescent substances related to the marine luciferin coelenterazine (λ_max = 465 nm) led us to attempt the synthesis of four nitrogen-rich pyridopyrazine-bearing analogues. Accordingly, the preparation of the corresponding benzyl-bearing pyridopyrazinols is studied. By varying the conditions for the condensation of phenylpyruvic acid with 1,2-diaminopyridine or 3,4-diaminopyridine, all the possible pyridopyrazin-2-ol regioisomers are isolated and properly characterized, including by means of crystallographic studies. The ensuing syntheses of the halogenated pyridopyrazines are fraught with difficulties ranging from extensive decomposition to an unexpected ring contraction. In one instance, the inherently reductive mixture of phosphorus oxychloride and phosphorus trichloride provides 2-benzyl-3-chloropyrido[2,3-b]pyrazine. This precursor is then transformed into the target O-acetylated luciferin (6,8-dibenzylimidazo[1,2-a]pyrido[3,2-e]pyrazin-9-yl acetate). The ‘benzo’ derivative of this analogue (i.e., 2,12-dibenzylimidazo[1′,2′:1,6]pyrazino[2,3-c]isoquinolin-3-yl acetate) is also prepared and the chemiluminescence emission spectra of these compounds are determined in a phosphate buffer (λ_max = 546 and 462 nm).

Key words

chemiluminescence - coelenterazine - imidazo[1,2-a]pyrazin-3(7H)-one - pyridopyrazine - luciferin - heterocycles - rearrangement

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References

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