Development of 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulfate sodium salt (INT-767): Process optimization, synthesis and characterization of metabolites

Mechanism of action of the bile acid receptor TGR5 in obesity

“…Cerra et al. 63 improved the synthesis of the TGR5/FXR double receptor agonist INT-767 and promoted the study of double receptor agonists. Dehmlow et al.…”

Merging Continuous Flow Technology, Photochemistry and Biocatalysis to Streamline Steroid Synthesis

“…Flow chemistry can be easily integrated into multistep synthesis, also in combination with batch steps to facilitate the conduction of critical reactions. In 2022, we described the scale‐up synthesis of the bile sulfate derivative INT‐767 ( 16 ) (Scheme 4), an FXR/TGR5 dual agonist with remarkable therapeutic potential for liver disorders [18] . Critical bottlenecks such as the side chain degradation were solved using flow technology.…”

“…In 2022, we described the scale-up synthesis of the bile sulfate derivative INT-767 (16) (Scheme 4), an FXR/TGR5 dual agonist with remarkable therapeutic potential for liver disorders. [18] Critical bottlenecks such as the side chain degradation were solved using flow technology. In particular, a telescoped one-pot two-step procedure was performed in a continuous mode without solvent switch using a readily assembled flow ozonolysis device (Scheme 4).…”

“…The flow set-up consisted of two calibrated rotary piston pumps, a micromixer element, a perfluoroalkoxy (PFA) reactor tubing heated in an oil-bath, a back-pressure regulator (BPR), and was assisted by reaction monitoring based on in-line ATR FT-IR and an off-line HPLC analysis. Experiments were conducted by pumping two feed solutions: one containing the steroidal substrate 17 (1:1, w w À 1 solution in tetralin) pre-heated at 90 °C and the second one containing deoxofluor (18). The optimal reaction conditions consisted in a residence time of 30 min, a temperature of 120 °C and the use of 3 equiv.…”