1.
Org Lett
; 16(16): 4142-5, 2014 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-25084526
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.
Subject(s)
Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Pyridines/chemical synthesis , Pyridines/pharmacology , Crystallography, X-Ray , Hydrogenation , Molecular Conformation , Molecular Structure , Pyridines/chemistry , Stereoisomerism
2.
Chemistry
; 18(6): 1577-81, 2012 Feb 06.
Article
in English
| MEDLINE
| ID: mdl-22238176