Promising anticancer drug thapsigargin: A perspective toward the total synthesis

ABSTRACT

The guaianolide ring containing sesquiterpene thapsigargin is found in the roots and fruits of Mediterranean plant Thapsia garganica L. It is known for its activity as a potent antagonist for Ca²⁺-ATPase (sarco–endoplasmic reticulum Ca²⁺-ATPase) inhibition. Recently, a prodrug mipsagargin is being investigated to target the blood vessel of the cancer cells for the treatment of tumors. The limited natural supply (low isolation and only localized growth (Mediterranean area)) from the natural sources strongly urges for the development of chemical synthetic strategies to access these natural products. This review pertain the various strategies used so far in the thapsigargin’s synthesis, focusing on major contributions in the total synthesis till date.

GRAPHICAL ABSTRACT

KEYWORDS:

• Anticancer
• Baran’s and Evans’ synthetic strategy
• Ley’s and Christensen’s approach
• Mipsagargin
• prodrug
• SERCA
• thapsigargin
• total synthesis
• tumors

Acknowledgments

This review is dedicated to Professor Søren Brøgger Christensen for his enormous contribution toward thapsigarin from the isolation, structure development, and synthesis to the development it as prodrug during last 40 years. Authors thanks Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA for the financial support.