Fluorescent triazolyl spirooxazolidines: Synthesis and NMR stereochemical studies

Abstract

Carbon-heteoratom chemistry is a method of choice for rapid construction of complex molecules. In the recent decade, its various applications flourished thanks to the click chemistry approach. Herein, we use a combination of C-X bond formation reactions to complete the synthesis of 1,2,3-triazolyl spirooxazolidines, bearing the fluorenylmethoxycarbonyl (fmoc) substituent. Thanks to the application of 2D-NMR spectroscopic methods and a multilevel computational approach, including a medicinal chemistry – inspired conformational search, PM7 semiempirical and DFT-based geometry optimization finalized with DFT-GIAO NMR shielding constant calculation, we were able to investigate the conformational space and assign cis/trans configuration in complex NMR spectra. For the obtained fmoc derivatives we recorded UV-VIS absorption and emission spectra. The obtained compounds contain pharmacophoric groups characteristic for endocannabinoid system modulators- CB1 receptor ligands or FAAH inhibitors.