The class
New synthesis route scales a polycyclic CETP inhibitor to multikilogram quantities (Org Lett 2014)
Original title: Facile entry to an efficient and practical enantioselective synthesis of a polycyclic cholesteryl ester transfer protein inhibitor
Researchers developed an efficient enantioselective synthesis of chiral polycyclic cholesteryl ester transfer protein (CETP) inhibitor 1, making the route practical for large-scale production. Key steps included a modified Hantzsch-type reaction to build the sterically hindered pyridine ring, enantioselective hydrogenation of a hindered ketone using a novel BIBOP-amino-pyridine-derived ruthenium complex, efficient ICl-promoted lactone formation, and a BF3-mediated hydrogenation step for diastereoselective lactol reduction. This route was successfully scaled to produce multikilogram quantities of the challenging CETP drug candidate, supporting its further development.
Original abstract
An efficient enantioselective synthesis of the chiral polycyclic cholesteryl ester transfer protein (CETP) inhibitor 1 has been developed. The synthesis was rendered practical for large scale via the development of a modified Hantzsch-type reaction to prepare the sterically hindered pyridine ring, enantioselective hydrogenation of hindered ketone 6 utilizing novel BIBOP-amino-pyridine derived Ru complex, efficient ICl promoted lactone formation, and a BF3 mediated hydrogenation process for diastereoselective lactol reduction. This efficient route was successfully scaled to produce multikilogram quantities of challenging CETP drug candidate 1.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.