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Three Efficient Methods for Preparation of Coelenterazine Analogues
Author(s) -
Shakhmin Anton,
Hall Mary P.,
Walker Joel R.,
Machleidt Thomas,
Binkowski Brock F.,
Wood Keith V.,
Kirkland Thomas A.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601111
Subject(s) - bioluminescence , chemistry , combinatorial chemistry , luciferase , biochemistry , gene , transfection
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.