Total Synthesis of Leupyrrin B1: A Potent Inhibitor of Human Leukocyte Elastase

The total synthesis of leupyrrin B1 was accomplished by an expedient strategy that involves an optimized HATU-mediated amide coupling protocol of elaborate substrates. The generally useful procedure was also successfully applied in an improved total synthesis of leupyrrin A1. Finally, leupyrrins A1...

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Bibliographic Details
Published in:Organic letters 2016-08, Vol.18 (16), p.3964-3967
Main Authors: Thiede, Sebastian, Wosniok, Paul R, Herkommer, Daniel, Schulz-Fincke, Anna-Christina, Gütschow, Michael, Menche, Dirk
Format: Article
Language:English
Subjects:
4-Butyrolactone - analogs & derivatives
4-Butyrolactone - chemical synthesis
4-Butyrolactone - chemistry
4-Butyrolactone - pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Humans
Leukocyte Elastase - antagonists & inhibitors
Leukocyte Elastase - metabolism
Molecular Structure
Structure-Activity Relationship
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Summary:The total synthesis of leupyrrin B1 was accomplished by an expedient strategy that involves an optimized HATU-mediated amide coupling protocol of elaborate substrates. The generally useful procedure was also successfully applied in an improved total synthesis of leupyrrin A1. Finally, leupyrrins A1 and B1 were evaluated toward a panel of proteases, and human leukocyte elastase was discovered as a molecular target of the leupyrrins.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.6b01724