On Pyridopyrazinol Chemistry: Synthesis of Chemiluminescent Substances

Our work on new chemiluminescent substances related to the marine luciferin coelenterazine (lambda(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 (lambda(max) = 546 and 462 nm).

Automated summary

Research on new chemiluminescent substances related to marine luciferin coelenterazine led to the synthesis of nitrogen-rich pyridopyrazine-bearing analogues, including the benzyl-bearing pyridopyrazinols. Challenges were faced in the synthesis of halogenated pyridopyrazines, with varying degrees of difficulties encountered. Despite these challenges, the target O-acetylated luciferin and its derivative were successfully prepared, with their chemiluminescence emission spectra determined.