Synthetic studies on polycyclic indole alkaloids

140 Pages·2016·1.16 MB·English

Iowa State University Capstones, Theses and
Retrospective Theses and Dissertations
Dissertations
2006
Synthetic studies on polycyclic indole alkaloids
Tao Wu
Iowa State University
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Wu, Tao, "Synthetic studies on polycyclic indole alkaloids " (2006).Retrospective Theses and Dissertations. 3057.
https://lib.dr.iastate.edu/rtd/3057
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Synthetic studies on polycyclic indole alkaloids
by
Tao Wu

A dissertation submitted to the graduate faculty
in partial fulfillment of the requirements for the degree of
DOCTOR OF PHILOSOPHY

Major: Organic Chemistry

Program of Study Committee:
George A. Kraus, Major Professor
Richard C. Larock
William S. Jenks
Jacob W. Petrich
Donald Lee Reynolds

Iowa State University
Ames, Iowa
2006
Copyright © Tao Wu, 2006. All rights reserved.
UMI Number: 3243539
UMI Microform3243539
Copyright2007 by ProQuest Information and Learning Company.
All rights reserved. This microform edition is protected against
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ii
TABLE OF CONTENTS

TABLE OF CONTENTS ii
LIST OF ABBREVIATION iv
ACKNOWLEGEMENT vii
ABSTRACT ix

GENERAL INTRODUCTION 1

CHAPTER I. HKI 0231A AND HKI 0231B SYNTHESES
Introduction 2
Results and Discussion 7
Experimental Section 24
References 47

CHAPTER II. SYNTHESIS OF ABEO-ERGOLINES AND THEIR ANALOGS
Introduction 51
Results and Discussion 58
Experimental Section 70
References 85

CHAPTER III. BENZOCYCLOBUTENOL CHEMISTRY
Introduction 89
iii
Results and Discussion 96
Experimental Section 109
References 123

GENERAL CONCLUSIONS 129
iv
LIST OF ABBREVIATIONS

AIBN azodiisobutyronitrile
app apparent
aq aqueous
Bn benzyl
br broad
Bu butyl
calcd calculated
CSA camphorsulfonic acid
δ chemical shift in ppm downfield from Me Si
4
d doublet
dd doublet of doublets
ddd doublet of doublets of doublets
DDQ 2,3-dicyano-5,6-dichloro-1,4-benzoquinone
DIPEA diisopropylethylamine
DMAP 4-(dimethylamino)pyridine
DME glyme
DMF N, N-dimethylformamide
DMSO dimethyl sulfoxide
DPPA diphenylphosphoryl azide
dt doublet of triplets
EI electron impact
equiv equivalent
g gram(s)
h hour(s)
Hz hertz
v
HMDS potassium bis(trimethylsilyl)amide
HMTA hexamethylene tetramine
HRMS high-resolution mass spectrum
IC inhibitory concentration 50%
50
J coupling constant
KHMDS potassium hexamethyldisilazamide
L liter(s)
LDA lithium diisopropylamide
LAH lithium aluminum hydride

LiTMP lithium 2,2,6,6-tetramethylpiperidide
μ micro
m milli, multiplet (NMR)
M moles per liter
mg milligram(s)
mmol millimole(s)
mp melting point
MHz megahertz
min minute(s)
mol mole(s)
mp melting point
m/z mass to charge ratio
NMP N-methylpyrrolidinone
NMR nuclear magnetic resonance
p para
PCC pyridinium chlorochromate
pH hydrogen ion concentration
ppm parts per million
vi
ppt precipitate
PPTS pyridinium 4-toluenesulfonate
q quartet
quint quintuplet
rt room temperature
s singlet (NMR)
t triplet
TBAC tetrabutylammonium chloride
TBAF tetrabutylammonium fluoride
TBS tert-butyldimethylsilyl
TFA trifluoroacetic acid
THF tetrahydrofuran
TLC thin layer chromatography
TMEDA N,N,N',N'-tetramethylethylenediamine
TMSCl trimethylsilyl chloride
UV ultraviolet
vii
Acknowledgements

First of all, I would like to thank my advisor Professor George A. Kraus for
allowing me to join his group and for all his support and advice over the years. He is a
brilliant chemist, as well as a wonderful teacher. I will never forget witnessing his many
creative ideas and how his training turned me into an organic chemist.
I would like to thank Professor Richard C. Larock for his letters of
recommendation. Rich is a brilliant chemist. His group has been the place for me to take
advice on transition-metal chemistry. And his big book has been the place for me when I
need information of organic transformations.
I would like to thank Professor William Jenks. I thank him for bringing chemistry
with fun to the classroom. As a devoted teacher, the door of his office is always open,
even for many of my silly questions. He seems to be always there ready to offer his
helpful discussions and suggestions.
I would like to thank Professor Jacob Petrich and Professor Donald Reynolds for
serving on my POS committee. I thank them for their time and suggestions. I thank
Professor John Verkade for his letters of recommendations.
I would like to thank all the current and former members of the Kraus group for
their friendship. It has been a wonderful experience being part of the group. Special
thanks to Dr. Jingqiang Wei, who offered his hands in and outside Gilman Hall; and to Dr.
Yi Yuan for his ready support on computer and literature search.
My time in the chemistry department has been fun because of the really fantastic
people I met here. I thank Dr. Chengxiang Zhou for initiating our discussion group and
relaxing tennis time; I thank Zhijian Liu for knowledge of palladium chemistry and I
thank Dr. Weiping Su for being a big brother to me. I thank John for his proof-reading on
viii
my thesis. I also should not forget to thank Jacob and Jesse for their frequent help with
my English.
My stay here at Iowa State would have been totally different without my wife
Liping’s support along the way. Her understanding and patience are essential for the
success of my graduate study.
I thank my daughter Irene. Her birth brightened my life. And I thank my mother
for her endless love and constant encouragement for me to be a better person.
Finally, thanks to all of my friends that I have met at Iowa State over the last five
years. I will always look back on my time at Iowa State with fondness.

Tao Wu

Ames, Iowa
August 2006