Synthesis of Novel Chiral Heterocyclic Compounds for Antibacterial Agents and Peptidomimetics

158 Pages·2013·0.72 MB·English

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University of New Orleans Theses and
Dissertations and Theses
Dissertations
12-15-2007
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Jean-Rene Ella-Menye
University of New Orleans
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Synthesis of Novel Chiral Heterocyclic Compounds for Antibacterial
Agents and Peptidomimetics

A Dissertation

Submitted to the Graduate Faculty of the
University of New Orleans
in partial fulfillment of the
requirements for the degree of

Doctor of Philosophy
In
The Department of Chemistry

By

Jean-René Ella-Menyé

M.S. Université Louis Pasteur (France) 2002
Pharm. D. Université Louis Pasteur (France) 2002

December 2007
Dedicated to:

My mother, Bernadette
My Father, Paul
My other mother and father, Georges and Rita

ii
Ackowledgements:
I would like to give a very special thank to my advisor, Dr. Guijun Wang for her guidance and
support throughout the 5 years I spent working with her at the University of New Orleans. I also
wish to thank my Ph.D. committee members, Dr. Mark L. Trudell, Dr. Branko Jursic, Dr.
Richard B. Cole and Dr. Steven P. Nolan. Thank you to my current and former group members,
Dr. Xiaoping Nie, Dr. Vibha Sharma, Sherwin Cheuk, Kris Williams, Michael St. Martin and
Navneet Goyal. I am grateful to the American Heart Association and the University of New
Orleans for the financial support. Thank you to the Laboratory for Advanced Applications in
GlycoChemistry for the biological testing and thank you to Professor R. I. Hollingsworth from
Michigan State University for providing the lactone starting material. Thank you to the Louisiana
State University Department of Chemistry for lending us lab space for a year during the Katrina
evacuation. Finally, I wish to offer my deepest gratitude to Dr. Clementine Féau, for her love and
constant support.

iii
Table of Contents
List of schemes.............................................................................................................................. vi
List of figures .............................................................................................................................. viii
List of tables.................................................................................................................................. ix
Abstract ...........................................................................................................................................x
Chapter 1: Introduction ................................................................................................................1
Part I: Chiral nitrogen and oxygen-containing molecules as building blocks for the synthesis of
biologically active molecules ...........................................................................................................1
Part II: Synthesis of rigid bicyclic aminoacids as building blocks for peptidomimetics ................8
References .....................................................................................................................................19
Chapter 2: Design and synthesis of new chiral 1,3-oxazinan-2-ones from carbohydrates
derivatives ......................................................................................................................................30
Abstract ..........................................................................................................................................30
Introduction ....................................................................................................................................31
Results and discussion ...................................................................................................................33
Conclusions ....................................................................................................................................40
Experimental section ......................................................................................................................41
References ......................................................................................................................................50
Chapter 3: Synthesis of Chiral 2-Oxazolidinones, 2-Oxazolines and Their Analogs ..................55
Abstract ..........................................................................................................................................55
Introduction ....................................................................................................................................56
Results and discussion ...................................................................................................................59
Conclusions ....................................................................................................................................67
Experimental section ......................................................................................................................68
References ......................................................................................................................................89

iv
Chapter 4: Synthesis and Antibacterial Activities of 1,3-Oxazinan-2-ones Derivatives ..............94
Abstract ..........................................................................................................................................94
Introduction ....................................................................................................................................95
Results and discussion ...................................................................................................................98
Conclusions ..................................................................................................................................105
Experimental section ....................................................................................................................106
References ....................................................................................................................................118
Chapter 5: Synthesis of a Ring-Oxygenated variant of the Choi core of Aeruginosin 298-A from
D-mannose ...................................................................................................................................121
Abstract ........................................................................................................................................121
Introduction ..................................................................................................................................122
Results and discussion .................................................................................................................129
Conclusions ..................................................................................................................................132
Experimental section ....................................................................................................................134
References ....................................................................................................................................144
Vita ..............................................................................................................................................147

v
List of Schemes
Scheme 1.1 .......................................................................................................................................3
Scheme 1.2 .......................................................................................................................................4
Scheme 1.3 .......................................................................................................................................4
Scheme 1.4 .......................................................................................................................................5
Scheme 1.5 .......................................................................................................................................5
Scheme 1.6 .......................................................................................................................................6
Scheme 1.7 .......................................................................................................................................6
Scheme 1.8 .......................................................................................................................................6
Scheme 1.9 .......................................................................................................................................7
Scheme 1.10 .....................................................................................................................................7
Scheme 1.11 ...................................................................................................................................12
Scheme 1.12 ...................................................................................................................................13
Scheme 1.13 ...................................................................................................................................14
Scheme 1.14 ...................................................................................................................................15
Scheme 1.15 ...................................................................................................................................16
Scheme 1.16 ...................................................................................................................................17
Scheme 2.1 .....................................................................................................................................33
Scheme 2.2 .....................................................................................................................................33
Scheme 2.3 .....................................................................................................................................35
Scheme 2.4 .....................................................................................................................................36
Scheme 2.5 .....................................................................................................................................39
Scheme 3.1 .....................................................................................................................................60
Scheme 3.2 .....................................................................................................................................61
Scheme 3.3 .....................................................................................................................................63
vi
Scheme 3.4 .....................................................................................................................................64
Scheme 3.5 .....................................................................................................................................65
Scheme 3.6 .....................................................................................................................................65
Scheme 3.7 .....................................................................................................................................66
Scheme 4.1 .....................................................................................................................................98
Scheme 4.2 .....................................................................................................................................99
Scheme 5.1 ...................................................................................................................................125
Scheme 5.2 ...................................................................................................................................126
Scheme 5.3 ...................................................................................................................................128
Scheme 5.4 ...................................................................................................................................130
Scheme 5.5 ...................................................................................................................................130
Scheme 5.6 ...................................................................................................................................131
Scheme 5.7 ...................................................................................................................................132

vii
List of figures
Figure 1.1 .........................................................................................................................................3
Figure 1.2 .......................................................................................................................................11
Figure 2.1 .......................................................................................................................................32
Figure 2.2 .......................................................................................................................................32
Figure 2.3 .......................................................................................................................................36
Figure 2.4 .......................................................................................................................................38
Figure 3.1 .......................................................................................................................................57
Figure 3.2 .......................................................................................................................................57
Figure 3.3 .......................................................................................................................................59
Figure 4.1 .......................................................................................................................................96
Figure 4.2 .......................................................................................................................................97
Figure 4.3 .....................................................................................................................................100
Figure 4.4 .....................................................................................................................................102
Figure 5.1 .....................................................................................................................................123
Figure 5.2 .....................................................................................................................................124
Figure 5.3 .....................................................................................................................................128

viii
List of Tables
Table 4.1 ......................................................................................................................................100

ix