학술논문
Facile Entry to an Efficient and Practical EnantioselectiveSynthesis of a Polycyclic Cholesteryl Ester Transfer Protein Inhibitor.
Document Type
Article
Author
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; Steigmiller, Sonja
Source
Subject
*ENANTIOSELECTIVE catalysis
*POLYCYCLIC compounds
*CHOLESTERYL ester transfer protein
*CHEMICAL inhibitors
*CYCLIC compounds synthesis
*
*
*
*
Language
ISSN
1523-7060
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]