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.

• Klíčová slova
• 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
• antitumorózní látky fytogenní chemie   izolace a purifikace   MeSH
• Apiaceae chemie   metabolismus   MeSH
• butyráty chemie   izolace a purifikace   MeSH
• furany chemie   izolace a purifikace   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádory farmakoterapie   patologie   MeSH
• ovoce chemie   metabolismus   MeSH
• oxid uhličitý chemie   MeSH
• rostlinné extrakty chemie   MeSH
• sarkoplazmatická Ca2+-ATPáza antagonisté a inhibitory   metabolismus   MeSH
• superkritická fluidní chromatografie metody   MeSH
• techniky syntetické chemie * MeSH
• thapsigargin analogy a deriváty   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• butyráty MeSH
• furany MeSH
• oxid uhličitý MeSH
• rostlinné extrakty MeSH
• sarkoplazmatická Ca2+-ATPáza MeSH
• thapsigargin MeSH
• trilobolide MeSH Prohlížeč