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A new approach towards the synthesis of Transtaganolides/Basiliolides: C-19 Terpenolides from Thapsia with SERCA-inhibiting Activity

Alkhamisi, Riham (2011) KOK820 20111
Chemical Engineering
Abstract
Abstract
The Transtaganolides/Basiliolides (T/B) are C-19 terpenolides found in the plants Thapsia Garganica L., Thapsia Transtagana Brot and Thapsia Villosa var. Villosa L. from the Umbelliferae family. Reports suggest that these compounds have reversible SERCA-inhibiting properties and therefore are of great interest for the treatment of neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease.
The ground structure of the T/B is tetracyclic and has 6 contiguous stereocenters, suggesting a difficult and very challenging synthesis. This of course attracted synthetic chemists who saw a great challenge in finding a synthetic path for the total synthesis of these C-19 terpenolides. Several groups from around the world have... (More)
Abstract
The Transtaganolides/Basiliolides (T/B) are C-19 terpenolides found in the plants Thapsia Garganica L., Thapsia Transtagana Brot and Thapsia Villosa var. Villosa L. from the Umbelliferae family. Reports suggest that these compounds have reversible SERCA-inhibiting properties and therefore are of great interest for the treatment of neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease.
The ground structure of the T/B is tetracyclic and has 6 contiguous stereocenters, suggesting a difficult and very challenging synthesis. This of course attracted synthetic chemists who saw a great challenge in finding a synthetic path for the total synthesis of these C-19 terpenolides. Several groups from around the world have been working towards the total synthesis, and most of them used an Ireland-Claisen rearrangement/intramolecular Diels-Alder reaction sequence as a key step. An intermediate with all carbon-carbon bonds from the T/B carbon skeleton has been obtained so far, however the total synthesis is yet to be completed as the introduction of a methyl ester needed for the last step proved very hard.28
A new approach for synthesizing a key intermediate for the total synthesis of Transtaganolides/Basiliolides has been attempted in order to reduce the amount of steps. This reaction path includes an alkynylation (addition of a terminal alkyne to an aldehyde), followed by a Tandem reaction (Stille like coupling followed by a cyclization reaction to get the important 2-pyranone derivative).
The starting material for the alkynylation reaction was made by TBDMS protection of 3-butyn-1-ol and the addition to the ethyl glyoxalate was catalyzed by the use of a rhodium-phosphine complex. This alkynylation returned a secondary alcohol which was activated by mesylation. The last step (the Tandem reaction) is yet to be performed as time was insufficient. (Less)
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author
Alkhamisi, Riham
supervisor
organization
course
KOK820 20111
year
type
H1 - Master's Degree (One Year)
subject
language
English
id
2204317
date added to LUP
2011-11-14 15:44:32
date last changed
2011-11-14 15:44:32
@misc{2204317,
  abstract     = {Abstract
The Transtaganolides/Basiliolides (T/B) are C-19 terpenolides found in the plants Thapsia Garganica L., Thapsia Transtagana Brot and Thapsia Villosa var. Villosa L. from the Umbelliferae family. Reports suggest that these compounds have reversible SERCA-inhibiting properties and therefore are of great interest for the treatment of neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease.
The ground structure of the T/B is tetracyclic and has 6 contiguous stereocenters, suggesting a difficult and very challenging synthesis. This of course attracted synthetic chemists who saw a great challenge in finding a synthetic path for the total synthesis of these C-19 terpenolides. Several groups from around the world have been working towards the total synthesis, and most of them used an Ireland-Claisen rearrangement/intramolecular Diels-Alder reaction sequence as a key step. An intermediate with all carbon-carbon bonds from the T/B carbon skeleton has been obtained so far, however the total synthesis is yet to be completed as the introduction of a methyl ester needed for the last step proved very hard.28
A new approach for synthesizing a key intermediate for the total synthesis of Transtaganolides/Basiliolides has been attempted in order to reduce the amount of steps. This reaction path includes an alkynylation (addition of a terminal alkyne to an aldehyde), followed by a Tandem reaction (Stille like coupling followed by a cyclization reaction to get the important 2-pyranone derivative).
The starting material for the alkynylation reaction was made by TBDMS protection of 3-butyn-1-ol and the addition to the ethyl glyoxalate was catalyzed by the use of a rhodium-phosphine complex. This alkynylation returned a secondary alcohol which was activated by mesylation. The last step (the Tandem reaction) is yet to be performed as time was insufficient.},
  author       = {Alkhamisi, Riham},
  language     = {eng},
  note         = {Student Paper},
  title        = {A new approach towards the synthesis of Transtaganolides/Basiliolides: C-19 Terpenolides from Thapsia with SERCA-inhibiting Activity},
  year         = {2011},
}