Three Efficient Methods for Preparation of Coelenterazine Analogues. Issue 30 (15th June 2016)

• Record Type: Journal Article
• Authors: Shakhmin, Anton; Hall, Mary P.; Walker, Joel R.; Machleidt, Thomas; Binkowski, Brock F.; Wood, Keith V.; Kirkland, Thomas A.
• Is Part Of: Chemistry. Volume 22:Issue 30(2016)
• Page Start: 10369
• Page End: 10375
• Publication Date: 2016-06-15
• Subjects: bio-organic chemistry -- coelenterazine analogues -- luciferase -- luminescence -- nitrogen heterocycles; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201601111
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The growing popularity of bioluminescent assays has highlighted the need for coelenterazine analogues possessing properties tuned for specific applications. However, the structural diversity of known coelenterazine analogues has been limited by current syntheses. Known routes for the preparation of coelenterazine analogues employ harsh reaction conditions that limit access to many substituents and functional groups. Novel synthetic routes reported here establish simple and robust methods for synthesis and investigation of structurally diverse marine luciferase substrates. Specifically, these new routes allow synthesis of coelenterazine analogues containing various heterocyclic motifs and substituted aromatic groups with diverse electronic substituents at the R 2 position. Interesting analogues described herein were characterized by their physicochemical properties, bioluminescent half‐life, light output, polarity and cytotoxicity. Some of the analogues represent leads that can be utilized in the development of improved bioluminescent systems. Abstract : Tuning coelenterazine analogues : Three simple synthetic routes towards structurally diverse marine luciferase substrates are presented (see figure). These new routes allow synthesis of coelenterazine analogues containing various heterocyclic motifs and substituted aromatic groups. The analogues were characterized by their physicochemical properties, bioluminescent half‐life, light output, polarity and cytotoxicity.