In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum, which contains a structurally related sesquiterpene lactone, trilobolide (Tb), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin.
Keywords: 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin; Laser trilobum cultivation; chemical synthesis; extraction; mipsagargin; optimization and scale-up; sarco/endoplasmic reticulum calcium ATPase (SERCA); sesquiterpene lactones; thapsigargin; trilobolide; trilobolide isolation from fruits.