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Towards a total synthesis of (–)-amphidinolide K : development of new radical cascade methods Campbell, Natalie E.
Abstract
(–)-Amphidinolide K, a novel 19-membered macrolide isolated by Kobayashi and coworkers, possesses cytotoxic activity against L1210 and KB cells in vitro. I have utilized our radical relay cyclization methodology to access the tetrahydrofuran ring in high diastereoselectivity from a readily accessible precursor. N-alkoxyphthalimides, when subjected to radical conditions, are able to generate oxygen radicals, which may undergo a 1,5-hydrogen atom transfer, and subsequently cyclize onto a nearby radical acceptor. I also extended this radical methodology towards the synthesis of a number of 5-membered carbo- and heterocycles. The 1,3-dimethyl stereocenters of our target natural product were accessed by utilizing the inherent C₂ symmetry of a simple diol precursor. Several methods to rapidly access a diene fragment of our target have been explored. A tandem ring-closing metathesis/cycloreversion strategy was originally sought, with a number of approaches towards the synthesis of the requisite sulfur-containing precursors. While this strategy was ultimately unsuccessful, it was the model inspiration for a tandem one-electron/pericyclic cascade approach. Commencing with simple alkyl aldehydes, we are now about to effect the synthesis of substituted 1,3-butadienes in a single step with high yields and diastereoselectivities. Details of this work and progress towards the total synthesis of (–)-amphidinolide K will be discussed herein.
Item Metadata
Title |
Towards a total synthesis of (–)-amphidinolide K : development of new radical cascade methods
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2014
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Description |
(–)-Amphidinolide K, a novel 19-membered macrolide isolated by Kobayashi and coworkers, possesses cytotoxic activity against L1210 and KB cells in vitro. I have utilized our radical relay cyclization methodology to access the tetrahydrofuran ring in high diastereoselectivity from a readily accessible precursor. N-alkoxyphthalimides, when subjected to radical conditions, are able to generate oxygen radicals, which may undergo a 1,5-hydrogen atom transfer, and subsequently cyclize onto a nearby radical acceptor. I also extended this radical methodology towards the synthesis of a number of 5-membered carbo- and heterocycles.
The 1,3-dimethyl stereocenters of our target natural product were accessed by utilizing the inherent C₂ symmetry of a simple diol precursor. Several methods to rapidly access a diene fragment of our target have been explored. A tandem ring-closing metathesis/cycloreversion strategy was originally sought, with a number of approaches towards the synthesis of the requisite sulfur-containing precursors. While this strategy was ultimately unsuccessful, it was the model inspiration for a tandem one-electron/pericyclic cascade approach. Commencing with simple alkyl aldehydes, we are now about to effect the synthesis of substituted 1,3-butadienes in a single step with high yields and diastereoselectivities.
Details of this work and progress towards the total synthesis of (–)-amphidinolide K will be discussed herein.
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Genre | |
Type | |
Language |
eng
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Date Available |
2014-09-04
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivs 2.5 Canada
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DOI |
10.14288/1.0135553
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2014-11
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivs 2.5 Canada