Bioorganic Chemistry
Manca Jurajevčič, Lena Grošelj, Luka Ciber, Uroš Grošelj, Katarina Petra van Midden, Nejc Petek, Bogdan Štefane, Marko Novinec, Jurij Svete
A series of twelve 3-alkylsulfanyl- and 3-(hetero)arylsulfanyl-substituted 4-oxo-4H-quinolizine and 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives 3a–l were obtained by visible light-promoted photoredox sulfanylation of 4-oxo-4H-pyrido[1,2-a]pyrimidine-3- (1a), 4- oxo-4H-quinolizine-3- (1b), and 5-oxo-5H-thiazolo[3,2-a]pyrimidine-6- diazonium tetrafluoroborate (1c) with disulfides 2a–d and thiols 7a–e. The title reactions are the rare examples of the use of heteroaryl diazonium salts in photoredox chemistry in general, while the photocatalytic sulfanylation using quinolizinone- and azino- and azolo-fused 4-pyrimidinone-diazonium salts is unprecedented, to our knowledge. This synthetic method takes place at room temperature under aerobic conditions and does not require a transition-metal catalyst. Therefore, the described photocatalytic sulfanylation of the title diazonium salts 1 is a useful synthetic tool for the preparation of 3-sulfanyl-substituted (aza)quinolizines - a class of compounds of particular interest due to their biological activities and optical properties. The applicability of the title compounds 1 in bioconjugation and fluorescent labeling was demonstrated by the successful binding of the diazonium salts 1a and 1b to the BSA protein under photocatalytic conditions, with the luminescent properties of the (aza)quinolizinyl residue allowing easy detection and quantification of the bioconjugates 1-BSA. Further studies are underway to determine the substrate (protein) scope and site-selectivity of bioconjugation with (aza)quinolizinyl diazonium salts 1.
Read article: Bioorg. Chem., 2025, 163, 108686
