Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000131.xml
Synfacts 2018; 14(12): 1215
DOI: 10.1055/s-0037-1611139
DOI: 10.1055/s-0037-1611139
Synthesis of Natural Products and Potential Drugs
Synthesis of BMS-932481
Further Information
Publication History
Publication Date:
19 November 2018 (online)
Key words
BMS-932481 - γ-secretase modulator - vinylogous dynamic kinetic resolution - asymmetric hydrogenation - Noyori asymmetric transfer hydrogenation - intramolecular hydroacylationSignificance
BMS-932481 is a γ-secretase modulator that is of interest for the treatment of Alzheimer’s disease. A six-step synthesis of BMS-932481 based on a vinylogous dynamic kinetic resolution (VDKR) of rac-E delivered the target molecule in 38% overall yield and >99% ee. The VDKR was a consequence of rapid epimerization via dienolate I.
#
Comment
An alternative seven-step synthesis of BMS-932481 based on a rhodium-catalyzed asymmetric hydrogenation of the alkene J proceeded in 16.3% overall yield and >99% ee. The high pressure of hydrogen required (1000 psi) and the expense of the rhodium catalyst were dis-advantageous to this route.
#
#