1. Facile Entry to an Efficient and Practical EnantioselectiveSynthesis of a Polycyclic Cholesteryl Ester Transfer Protein Inhibitor.
- Author
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Han, Zhengxu S., Xu, Yibo, Fandrick, Daniel R., Rodriguez, Sonia, Li, Zhibin, Qu, Bo, Gonnella, Nina C., Sanyal, Sanjit, Reeves, Jonathan T., Ma, Shengli, Grinberg, Nelu, Haddad, Nizar, Krishnamurthy, Dhileep, Song, Jinhua J., Yee, Nathan K., Pfrengle, Waldemar, Ostermeier, Markus, Schnaubelt, Jürgen, Leuter, Zeno, and Steigmiller, Sonja
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ENANTIOSELECTIVE catalysis , *POLYCYCLIC compounds , *CHOLESTERYL ester transfer protein , *CHEMICAL inhibitors , *CYCLIC compounds synthesis - Abstract
An efficient enantioselective synthesisof the chiral polycycliccholesteryl ester transfer protein (CETP) inhibitor 1has been developed. The synthesis was rendered practical for largescale via the development of a modified Hantzsch-type reaction toprepare the sterically hindered pyridine ring, enantioselective hydrogenationof hindered ketone 6utilizing novel BIBOP-amino-pyridinederived Ru complex, efficient ICl promoted lactone formation, anda BF3mediated hydrogenation process for diastereoselectivelactol reduction. This efficient route was successfully scaled toproduce multikilogram quantities of challenging CETP drug candidate 1. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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