Thapsigargin: a promising natural product with diverse medicinal potential - a review of synthetic approaches and total syntheses.

Thapsigargin, a sesquiterpene lactone, naturally occurring in the roots and fruits of the Mediterranean shrub Thapsia garganica L, is known to the practitioners of traditional medicines since the medieval ages as a cure for rheumatic pain, lung diseases, and female infertility. This naturally occurring guaianolide has shown remarkable activity for Sarco endoplasmic reticulum Ca2+ ATPase inhibition, which eventually renders it fit as a potential candidate for anti-cancer drugs. Mipsagargin, a prodrug derived from thapsigargin, is under clinical trials for the treatment of glioblastoma. Recently, thapsigargin has shown promise as an antiviral against SARS-CoV-2. Limited natural availability and challenging synthesis have prompted research into new synthetic pathways. This review discusses significant synthetic approaches and total syntheses of thapsigargin reported to date.