A new approach towards the synthesis of Transtaganolides/Basiliolides: C-19 Terpenolides from Thapsia with SERCA-inhibiting Activity
(2011) KOK820 20111Chemical Engineering (M.Sc.Eng.)
- 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)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/2204317
- author
- Alkhamisi, Riham
- supervisor
-
- Rikard Larsson LU
- Olov Sterner LU
- Martin H Johansson LU
- organization
- course
- KOK820 20111
- year
- 2011
- 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}},
}