Direct 3-Acylation of Indolizines by Carboxylic Acids for the Practical Synthesis of Red Light-Releasable Caged Carboxylic Acids

Abstract

To enhance the practicality of photouncaging system using 3-acyl-2methoxyindolizines, direct acylation of indolizines with carboxylic acids was developed using condensation reagents, generally used for peptide coupling. This method allowed for caging a broad range of carboxylic acids with indolizines. The method enabled a facile synthesis of water-soluble caged bioactive carboxylic acids having an intramolecular photosensitizer. The efficient release of carboxylic acids from the synthesized caged compounds upon red light irradiation was confirmed in neutral buffered solutions.

Photocatalytic C–H Disulfuration for the Preparation of Indolizine-3-disulfides

“…Based on the above experimental results and related literature reports, , a possible reaction mechanistic pathway is shown in Scheme . First of all, the photocatalyst RB was motivated into an excited state RB* under visible light irradiation.…”

“…Preparation of drug molecules containing indolizine scaffold by direct C-3 functionalization modification is a typical strategy. It has been reported successively that cyanation, halogenation, heteroarylation, sulfuration, selenylation, dicarbonylation, sulfonylation, acylation, and carboxamidation can take place at the C-3 position of indolizine. , However, the disulfuration in the C-3 position of indolizine has been rarely reported. According to our interest in disulfides and based on our previous work, we developed a straightforward strategy for visible-light-induced sp 3 C–H disulfuration using rose bengal (RB) as a photocatalyst.…”

Red light-induced conjugation of amines through amide bond formation triggered via photooxidation of 3-acylindolizines

“…We recently reported a 3-acylindolizine-based photouncaging system that liberates carboxylic acids from indolizines upon red-light irradiation in the presence of a sensitizer such as methylene blue (Fig. 1c ) 14 , 15 . Although the indolizine core is chemically stable, it is responsive to singlet oxygen to produce β-pyridylacrylic acids or the corresponding esters by capturing a solvent molecule such as water or alcohols, respectively, with the release of carboxylic acids 16 .…”

Copper‐Promoted Direct Decarboxylative C3‐Acylation of Electron‐Rich Indolizines Using α‐Keto Acids

“…Despite these significant advances, transition metal-catalyzed decarboxylative acylation on electron-rich heterocycles remains rarely reported. [36][37][38][39][40][41][42] As part of our program, we are exploring novel fluorophores for cell imaging. [43][44][45][46][47][48][49][50][51][52][53][54][55] For this purpose, we are interested in the direct synthesis of C-3-acylated indolizines via CÀ H activation.…”

“…Ortho‐aryl acylation with different directing groups (N‐heterocycles, [30] amides, [31] carbamates, [32] nitrosoanilines, [33] ketones, [34] azobenzene [35] ) has also gained interest. Despite these significant advances, transition metal‐catalyzed decarboxylative acylation on electron‐rich heterocycles remains rarely reported [36–42] …”