A Multistep Flow Process for the Synthesis of Highly Functionalized Benzoxazoles

An efficient and scalable transformation of 3-halo-<i>N</i>-acyl anilines to the corresponding benzoxazoles within a continuous flow reactor is reported. This transformation proceeds <i>via</i> base-mediated deprotonation, ortho-lithiation, and intramolecular cyclization to provide unstable lithiated benzoxazole moieties. The subsequent in-line electrophilic quench results in the formation of substituted benzoxazoles in high yield and quality. Continuous flow technology allowed for accurate temperature control and immediate in-line quench while minimizing the hold-up time for the unstable lithiated intermediates thereby minimizing associated byproduct formation

Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators

Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGR5 agonist. Chemical modifications of this compound resulted in the disclosure of 6α-ethyl-16-<i>epi</i>-avicholic acid that shows enhanced potency at TGR5 and FXR receptors. The synthesis, biological appraisals, and structure–activity relationships of this series of compounds are herein described. Moreover, a thorough physicochemical characterization of 6α-ethyl-16-<i>epi</i>-avicholic acid as compared to naturally occurring bile acids is reported and discussed