Natural Products Responsible for Bioluminescence: Synthesis of Coelenterazines and Dehydrocoelenterazines

摘要

Bioluminescent systems have received a great attention due to their unique capability to monitor biological components, such as ATP, Ca2+ ion, and reactive oxygen species (ROS), by emitting light. Coelenterazine (CL) is the organic substance for the chromophore of aequorin, which emits blue light in the presence of Ca2+ ion. Dehydrocoelenterazine (DCL) is the organic substance for bioluminescence of symplectin and pholasin that emit light in the presence of ROS. DCL is prepared by oxidation of CL, and a synthetic route for CL had already established more than 50 years ago. Condensation of coelenteramine and alpha-ketoaldehyde affords CL, which has imidazo-[1,2-a] pyrazine-3(7H)-one core structure. However, the synthetic route is not efficient when many varieties of CL or DCL analogs are required. Therefore, many researchers have paid their efforts in order to obtain those analogs. Cross-coupling reaction is the most powerful method for functionalizing of 2-aminopyrazines into coelenteramine analogs, which are important components for the synthesis of CL analogs. This review describes the synthesis of CL and DCL, and alternative methods for synthesis of their analogs.