Transaminases Provide Key Chiral Building Blocks for the Synthesis of Selective M1/M4 Agonists.
ACS medicinal chemistry letters(2023)
摘要
We 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.
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关键词
selective CHRM4 agonist,biocatalysis,asymmetricsynthesis,muscarinic receptors,bifunctional aminebuilding blocks,aminotransferase
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