Total synthesis of five thapsigargins: guaianolide natural products exhibiting sub-nanomolar SERCA inhibition.

Journal article

Herein we describe the total synthesis of five guaianolide natural products: thapsigargin, thapsivillosin C, thapsivillosin F, trilobolide and nortrilobolide. Prodrug derivatives of thapsigargin have shown selective in vivo cytotoxicity against prostate tumours and the need for further investigation of this phenomenon highlights the importance of these total syntheses. The first absolute stereochemical assignment of thapsivillosin C is also delineated.

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

• Publication status: Published
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany)
• Volume: 13
• Issue: 20
• Pages: 5688-5712
• Publication date: 2007-01-01
• DOI: 10.1002/chem.200700302
• EISSN: 1521-3765
• ISSN: 0947-6539
• Language: English
• Keywords: Enzyme Inhibitors; Stereoisomerism; Dose-Response Relationship, Drug; Molecular Structure; Nanotechnology; Sesquiterpenes, Guaiane; Cyclization; Biological Factors; Endoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Thapsigargin; Alkenes