Recent progress in the synthesis of firefly luciferin derivatives

Bioluminescent is a standard noninvasive technique for in vivo imaging. Bioluminescent screenings are based on the generation of light during interaction of luciferase with an appropriate substrate: D-luciferin (LH2), aminoluciferin (NH2-LH2) or theirs derivatives. Although there has been meaningful progress in the synthesis of the LH2, H2N-LH2 and their analogues, still a major synthetic challenge is to obtain luciferins, with red shifted luminescence and emission efficiency comparable to that of native luciferin emission. Over the last decade, by using different methods, a lot of analogues of luciferin/aminoluciferin have been synthesized, and therefore, in this review, we have summarized the recent progress in the design and synthesis of synthetic luciferins in a manner that all readers can be inspired to use, and/or design, and/or develop the useful far red/NIR bioluminescent substrates for luciferase.