ml3c00331_si_001.pdf (797.29 kB)
Transaminases Provide Key Chiral Building Blocks for the Synthesis of Selective M1/M4 Agonists
journal contribution
posted on 2023-11-06, 14:00 authored by Christopher
G. Thomson, Kelly Boss, Amy Calhoun, Cary Fridrich, Kevin M. Gardinier, Edward C. Hall, Keith Jendza, Louise Kirman, Nancy Labbé-Giguere, Kurt Laumen, Ming Qian, Sanjit Sanyal, Michael D. Shultz, Radka Snajdrova, Kian Tan, Kate Yaping Wang, Fan Yang, Feng Gao, Tao Hong, Elena Dale, Brent Kuzmiski, Danny Ortuno, Daniel S. PalaciosWe have developed a chiral route toward the synthesis
of muscarinic
M4 agonists that was enabled by the biocatalytic synthesis of the
key spirocyclic diamine building blocks 10 and 12. Using these bifunctional compounds we were able to optimize
a synthetic sequence toward a collection of advanced intermediates
for further elaboration. These advanced intermediates were then used
as starting points for early medicinal chemistry and the identification
of selective M1/M4 agonists.
