Stereoselective Synthesis of a Potent Thrombin Inhibitor by a Novel P2−P3 Lactone Ring Opening
- 1 May 2004
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 69 (11) , 3620-3627
- https://doi.org/10.1021/jo035794p
Abstract
The concise synthesis of a potent thrombin inhibitor was accomplished by a mild lactone aminolysis between an orthogonally protected bis-benzylic amine and a diastereomerically pure lactone. The lactone was synthesized by the condensation of l-proline methyl ester with an enantiomerically pure hydroxy acid, which in turn was synthesized by a highly stereoselective (>500:1 er) and productive (100,000:1, S/C) enzymatic reduction of an alpha-ketoester. In addition, a second route to the enantiomerically pure lactone was accomplished by a diastereoselective ketoamide reduction.Keywords
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