Practical chemoenzymatic synthesis of a 3-pyridylethanolamino β3 adrenergic receptor agonist

John Y.L. Chung, Guo Jie Ho, Michel Chartrain, Chris Roberge, Dalian Zhao, John Leazer, Roger Farr, Micheal Robbins, Kateeta Emerson, David J. Mathre, James M. McNamara, David L. Hughes, Edward J.J. Grabowski, Paul J. Reider

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36 Scopus citations

Abstract

A chemoenzymatic synthesis of β3 agonist 1 suitable for large scale preparation is described. The key chiral 3-pyridylethanolamine intermediate (R)-7 was prepared via an improved Neber rearrangement and a yeast-mediated asymmetric reduction. The tetrazolone fragment of the molecule was constructed via a dipolar cycloaddition between 1-(cyclopentyl)-3-propylazide and p-chlorosulfonyl phenylisocyanate. Sulfonamide coupling of these two intermediates under Shotten-Baumann conditions, followed by a borane reduction of the amide afforded 1 in 20-32% overall yield from 3-acetylpyridine.

Original languageEnglish (US)
Pages (from-to)6739-6743
Number of pages5
JournalTetrahedron Letters
Volume40
Issue number37
DOIs
StatePublished - Sep 10 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Chung, J. Y. L., Ho, G. J., Chartrain, M., Roberge, C., Zhao, D., Leazer, J., Farr, R., Robbins, M., Emerson, K., Mathre, D. J., McNamara, J. M., Hughes, D. L., Grabowski, E. J. J., & Reider, P. J. (1999). Practical chemoenzymatic synthesis of a 3-pyridylethanolamino β3 adrenergic receptor agonist. Tetrahedron Letters, 40(37), 6739-6743. https://doi.org/10.1016/S0040-4039(99)01353-2