930280-05-0Relevant academic research and scientific papers
Total synthesis of thapsigargin, a potent SERCA pump inhibitor
Ball, Matthew,Andrews, Stephen P.,Wierschem, Frank,Cleator, Ed,Smith, Martin D.,Ley, Steven V.
, p. 663 - 666 (2008/02/05)
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 C3-0. 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).
Total synthesis of five thapsigargins: Guaianolide natural products exhibiting sub-nanomolar SERCA inhibition
Andrews, Stephen P.,Ball, Matthew,Wierschem, Frank,Cleator, Ed,Oliver, Steven,Hoegenauer, Klemens,Simic, Oliver,Antonello, Alessandra,Huenger, Udo,Smith, Martin D.,Ley, Steven V.
, p. 5688 - 5712 (2008/02/13)
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.
