Development of a novel stereo-selective synthetic route towards Pumiliotoxin C, potent neurotoxin, via asymmetric Diels-Alder and sequential protonation-nucleophilic addition as key reaction steps Public
Mwenda, Edward (2012)
Abstract
The study towards the synthesis of the naturally occurring
(-)-pumiliotoxin C of the
dendrobatid alkaloid has been outlined. The bicyclic skeleton of
the pumiliotoxin C was be
rapidly assembled in one key reaction step using a novel regio- and
enantiocontrolled
asymmetric [4+2] cycloaddition of
TpMo(CO)2(3-alkenyl-η3-4,5,6-pyridinyl) diene 39. Diene
39
was formed from the TpMo(CO)2(η3-5-oxo-pyridinyl)
scaffold 27 via a Grignard reaction and
dehydration reaction. This was later followed by sequential
protonation-nucleophilic addition as
key reaction step for the introduction of the alkyl side
chain.
Table of Contents
Table of Contents:
1.
Introduction…………………………………………………………………………………..12
2. Results and
Discussion…………..…………………………………………………………..25
3.
Conclusion…………………………………………………………………………………...38
4.
Experimentals………………………………………………………………………………..40
List of Schemes:
Scheme 1: Total synthesis of (-)-pumiliotoxin C by
Oppolzer……………………………….….13
Scheme 2: Total synthesis of (-)-pumiliotoxin C by
Comins…………………………………….14
Scheme 3: Total synthesis of (-)-pumiliotoxin C by
Feringa………………………….…………15
Scheme 4: Total synthesis of (-)-pumiliotoxin C by
Overman..…………………………………16
Scheme 5: Total synthesis of (-)-pumiliotoxin C by
Back…...……..…………….……………...17
Scheme 6: [4 + 2] cycloaddition of diene
30…………………….…..…………………………..21
Scheme 7: [4 + 2] cycloaddition/demetallation sequence provides
2,6-cis tetrahydrochromes....22
Scheme 8: Retrosynthetic
analysis……………………………….…..…………………………..23
Scheme 9: Summary of results achieved by Shuangpei
Liu….….…..…………………………..24
Scheme 10: Proposed modification of (±)-pumiliotoxin
C...…….…..…………………………..24
Scheme 11: Preperation of Cbz-protected Molybdenum Scaffold
(±)-27…..….………………..25
Scheme 12: Synthesis of Tricholomalides
B…..….……………………………………………..26
Scheme 13: Formation of diene
(±)-39…..….………………………………………..…...……..28
Scheme 14: Dienophiles explored for the [4 + 2]
cycloaddition……..……..….………………..28
Scheme 15: [4 + 2] cycloaddition of with phenyl vinyl
sulphone.…..…………………………..29
Scheme 16: Lewis acid promoted [4 + 2] cycloaddition of
(±)-39…..…..………..……………..30
Scheme 17: Proposed mechanism for cycloaddition of
(±)-39...…….…..……………..………..30
Scheme 18: Consecutive Diels-Alder-Decarbonylation
reaction………………………………..33
Scheme 19: Protonation-Nucleophilic addition
reaction……….………………………………..35
Scheme 20: Complementary demetallation
protocols………….………………………………..38
Scheme 21: Summary of the progress
made……………………………………………………39
About this Master's Thesis
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Development of a novel stereo-selective synthetic route towards Pumiliotoxin C, potent neurotoxin, via asymmetric Diels-Alder and sequential protonation-nucleophilic addition as key reaction steps () | 2018-08-28 16:10:52 -0400 |
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