Total synthesis of thapsigargin, a potent SERCA pump inhibitor.

Journal article

The enantioselective total synthesis of thapsigargin, a potent, selective inhibitor of the Ca2+ pump SERCA, is described. Starting from ketoalcohol 8, key steps involve regioselective introduction of the internal olefin at C4-C5, judicious protecting group choice to allow chelation-controlled reduction at C3, and chemoselective introduction of the angelate ester function at C3-O. A selective esterification approach completes the total synthesis in a total of 42 steps and 0.61% overall yield (88.6% average yield per step). [reaction: see text].

Authors: Ball, M; Andrews, S; Wierschem, F; Cleator, E; Smith, M

• Publication status: Published
• Journal: Organic letters
• Volume: 9
• Issue: 4
• Pages: 663-666
• Publication date: 2007-02-01
• DOI: 10.1021/ol062947x
• EISSN: 1523-7052
• ISSN: 1523-7060
• Language: English
• Keywords: Alkenes; Enzyme Inhibitors; Chelating Agents; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Alcohols; Oxidation-Reduction; Thapsigargin; Stereoisomerism; Indicators and Reagents