Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8- O-(12-Aminododecanoyl)-8- O-Debutanoylthapsigargin
- PMID: 33291419
- PMCID: PMC7762042
- DOI: 10.3390/biom10121640
Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8- O-(12-Aminododecanoyl)-8- O-Debutanoylthapsigargin
Abstract
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.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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