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,
• MeSH
• Apiaceae chemistry   metabolism   MeSH
• Butyrates chemistry   isolation & purification   MeSH
• Furans chemistry   isolation & purification   MeSH
• Antineoplastic Agents, Phytogenic chemistry   isolation & purification   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Neoplasms drug therapy   pathology   MeSH
• Fruit chemistry   metabolism   MeSH
• Carbon Dioxide chemistry   MeSH
• Plant Extracts chemistry   MeSH
• Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors   metabolism   MeSH
• Chromatography, Supercritical Fluid methods   MeSH
• Chemistry Techniques, Synthetic * MeSH
• Thapsigargin analogs & derivatives   isolation & purification   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Butyrates MeSH
• Furans MeSH
• Antineoplastic Agents, Phytogenic MeSH
• Carbon Dioxide MeSH
• Plant Extracts MeSH
• Sarcoplasmic Reticulum Calcium-Transporting ATPases MeSH
• Thapsigargin MeSH
• trilobolide MeSH Browser