Synthesis of analogues and derivatives of luciferin for imaging techniques

The advent of genetic engineering has considerably affected the field of drug discovery and within this field of research, a good success has been the generation of a transgenic (ERE-Luc) mouse that has been transfected with a luciferase reporter gene. Under the control of activated estrogen receptors, this mouse encodes the enzyme luciferase, whose activity can be detected by chemiluminescent methods. The enzyme luciferase is able to catalyze the oxidative decarboxylation of D-luciferin with production of photons. The PhD project was aimed to the synthesis of compounds that should be characterized by a high affinity towards luciferase and could be used to monitor the expression of the enzyme utilizing different imaging techniques (BLI, MRI, PET). We have addressed our project towards the synthesis of substituted 2-cyano-6-hydroxybenzothiazole that could lead to differently substituted D-luciferin analogues and derivatives for BLI, MRI, or PET imaging. MRI and PET rely on the introduction of fluorine in the molecule (19F for MRI and 18F for PET). We have also realized a new, more versatile approach that could be applied to the synthesis of variously substituted luciferins. The overall approach starts from 1,4-benzoquinone and could be extended to the synthesis of variously substituted 1,4-benzoquinones.Yields of D-luciferin are in the range of 27-32% that are higher than existing methods and the use of toxic or poisonous reagents is avoided.