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 language | English (US) |
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Pages (from-to) | 6739-6743 |
Number of pages | 5 |
Journal | Tetrahedron Letters |
Volume | 40 |
Issue number | 37 |
DOIs | |
State | Published - Sep 10 1999 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Drug Discovery
- Organic Chemistry