Modern Tools for the Synthesis of Complex Bioactive Molecules E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 861

Veröffentlichungsjahr: 2012

Beschreibung

All the latest tools needed to plan and perform the synthesis of complex bioactive molecules Focusing on organic, organometallic, and bio-oriented processes, this book explores the impact and use of the latest synthetic tools for the synthesis of complex biologically active compounds. Readers will discover step by step how these synthetic tools have provided new, elegant solutions to many synthetic puzzles. Moreover, they will discover innovative methods that make it possible to control the exact connectivity of atoms within a molecule in order to set precise three-dimensional arrangements. Modern Tools for the Synthesis of Complex Bioactive Molecules features sixteen chapters, each one written by one or more leading experts in organic synthesis from around the world. It covers a broad range of topics that enable readers to take advantage of the latest methods for synthesizing complex molecules, including: * Modern catalysis, emphasizing key transformations such as C-H functionalizations, cross-couplings, gold-catalyzed reactions, metathesis-based syntheses, and asymmetric organocatalysis * Eco-compatible transformations, including rearrangements and domino reactions * Tools for the synthesis of carbohydrates and alkaloids * New techniques, including the use of fluorous tags and engineered biosynthesis The last two chapters explore target- and diversity-oriented organic synthesis as well as the use of DNA-based asymmetric catalysis, which are all promising tools for the successful synthesis of complex bioactive molecules. Modern Tools for the Synthesis of Complex Bioactive Molecules is ideal for students and researchers who need to plan and perform the synthesis of complex molecules as efficiently as possible. The book's expert advice will help these readers quickly resolve a broad range of problems that can arise in organic syntheses.

Leseprobe

Contents

Cover

Title Page

Copyright

Foreword

Preface

Contributors

Chapter 1: C–H Functionalization: A New Strategy for the Synthesis of Biologically Active Natural Products

1.1 Introduction

1.2 Palladium(0)-Catalyzed Intramolecular Direct Arylation

1.3 Palladium(0)-Catalyzed Intramolecular Alkenylation of sp2 C–H Bonds

1.4 Palladium(0)-Catalyzed Intramolecular Arylation of sp3 C–H Bonds

1.5 Palladium(II)-Mediated Intramolecular Oxidative Alkenylation of sp2 C–H Bonds

1.6 Directing Group-Assisted Palladium(II)-Enabled Carbon–Carbon Bond Formation at sp3 C–H Bonds

1.7 Platinum(II)-Mediated Alkane Dehydrogenation

1.8 Palladium(II)-Enabled Carbon–Oxygen Bond Formation at sp3 C–H Bonds

1.9 Iridium-Catalyzed Borylation of sp2 C–H Bonds

1.10 Rhodium(I)-Catalyzed Intramolecular Directed Alkylation of sp2 C–H Bonds

1.11 Rhodium(III)-Catalyzed Synthesis of Nitrogen-Containing Heterocycles

1.12 Conclusion

References

Chapter 2: The Negishi Cross-Coupling in the Synthesis of Natural Products and Bioactive Molecules

2.1 Introduction

2.2 Synthesis of Natural Products

2.3 Large-Scale Synthesis of Biologically Active Molecules

2.4 Conclusion

References

Chapter 3: Metal-Catalyzed C–Heteroatom Cross-Coupling Reactions

3.1 General Introduction

3.2 Buchwald–Hartwig-Type Reactions

3.3 Ullmann-Type Reactions

3.4 Miscellaneous

3.5 Conclusion

References

Chapter 4: Golden Opportunities in the Synthesis of Natural Products and Biologically Active Compounds

4.1 Introduction

4.2 Gold-Catalyzed Formation of Oxygen-Containing Heterocycles

4.3 Gold-Catalyzed Formation of Nitrogen-Containing Heterocycles

4.4 Gold-Catalyzed Formation of Carbocycles

4.5 Other Gold-Catalyzed Reactions

4.6 Conclusion

References

Chapter 5: Metathesis-Based Synthesis of Complex Bioactives

5.1 Introduction

5.2 Ring-Closing Olefin Metathesis

5.3 Ring-Closing Alkyne Metathesis

5.4 Alkene Cross-Metathesis

5.5 Enyne Metathesis

5.6 Tethered Metathesis

5.7 Relay Metathesis

5.8 Tandem Metathesis

5.9 Asymmetric RCM and ROM

5.10 Conclusion

References

Chapter 6: Enantioselective Organocatalysis: A Powerful Tool for the Synthesis of Bioactive Molecules

6.1 Introduction

6.2 Carbon–Carbon Bond Formation

6.3 Heteroatom Installation

6.4 Cascade Reaction

6.5 Conclusion

References

Chapter 7: Asymmetric Phase-Transfer Catalysis

7.1 Introduction

7.2 Alkylation

7.3 Michael Addition

7.4 Aldol and Mannich Reactions

7.5 Epoxidation and Aziridination

7.6 Strecker Reaction

7.7 Cyclization

7.8 Amination

7.9 Fluorination

7.10 Conclusion

References

Chapter 8: Rearrangements in Natural Product Synthesis

8.1 Introduction

8.2 The Cope and Oxy-Cope Rearrangements

8.3 The Claisen Rearrangement

8.4 The Overman Rearrangement

8.5 The Petasis–Ferrier Rearrangement

8.6 The Prins-Pinacol Rearrangement

8.7 The [1,2]- and [2,3]-Wittig Rearrangements

8.8 The Meyer–Schuster and Rupe Rearrangements

References

Chapter 9: Domino Reactions in the Enantioselective Synthesis of Bioactive Natural Products

9.1 Introduction

9.2 Cationic Domino Reactions

9.3 Anionic Domino Reactions

9.4 Radical Domino Reactions

9.5 Pericyclic Reactions

9.6 Photochemically Induced Domino Reactions

9.7 Transition Metal-Catalyzed Domino Reactions

9.8 Oxidative or Reductive Domino Reactions

References

Chapter 10: Fluorous Linker-Facilitated Synthesis of Biologically Interesting Molecules

10.1 Introduction

10.2 Fluorous Protective Linker for the Synthesis of Natural Product Analogues

10.3 Fluorous Displaceable Linkers for the Synthesis of Heterocyclic Compounds

10.4 Fluorous Diversity Oriented Synthesis (DOS)

10.5 Fluorous Mixture Synthesis

10.6 Summary

Acknowledgments

References

Chapter 11: The Evolution of Immobilized Reagents and Their Application in Flow Chemistry for the Synthesis of Natural Products and Pharmaceutical Compounds

11.1 Background

11.2 Multistep Synthesis of Natural Products and Bioactive Materials Using Immobilized Reagents

11.3 Flow Chemical Synthesis

11.4 Flow Synthesis of Chemical Building Blocks

11.5 Multistep Flow Synthesis of Natural Products and Pharmaceutical Compounds

11.6 Conclusion

References

Chapter 12: Synthetic Approaches to Bioactive Carbohydrates

12.1 Introduction

12.2 1,2-cis-Equatorial Glycosides

12.3 1,2-trans-Equatorial Linkages

12.4 1,2-cis-Axial Glycosides

12.5 α-Sialic Acid Glycosides

12.6 Uronic Acid Glycosides

12.7 β-Arabinofuranosides

12.8 Conclusion

References

Chapter 13: Ammonium Ylides as Building Blocks for Alkaloid Synthesis

13.1 Introduction

13.2 Ammonium 1,3-Ylides

13.3 1,2-Ammonium Ylides

13.4 Conclusion

Acknowledgment

References

Chapter 14: Precursor-Directed Biosynthesis of Polyketide and Nonribosomal Peptide Natural Products

14.1 Introduction

14.2 Natural Product Biosynthesis

14.3 Precursor-Directed Biosynthesis

14.4 Applications of Precursor-Directed Biosynthesis

14.5 Conclusion

Acknowledgments

References

Chapter 15: Target-Oriented and Diversity-Oriented Organic Synthesis

15.1 Introduction

15.2 Target-Oriented and Diversity-Oriented Synthesis

15.3 Alternative Approaches to Identifying Biologically Active Small Molecules

15.4 Strategies to Create Structurally Complex and Diverse Small Molecules

15.5 Recent Examples of Chemoselective Reactions Used in DOS

15.6 Biologically Active Small Molecules Obtained from DOS

15.7 Perspectives

Abbreviations

Acknowledgments

References

Chapter 16: DNA as a Tool for Molecular Discovery

16.1 Deoxyribozymes

16.2 DNA-Templated Synthesis

16.3 DNA-Encoded Chemical Libraries

16.4 DNA-Based Asymmetric Catalysis

16.5 Summary

References

Index

Copyright © 2012 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.

Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Cossy, Janine.

Modern tools for the synthesis of complex bioactive molecules / edited by Janine Cossy and Stellios Arseniyadis.

ISBN 978-0-470-61618-5 (hardback)

Foreword

Thanks to a rich evolution over the past century, organic synthesis has allowed the preparation of complex molecules and new materials with incredible properties. One of the main challenges is to find new and better ways to access complex molecules in an atom- and step-economical process (ASEP). To this end, novel and highly selective reagents and chemical reactions have been developed.

This book, Modern Tools for the Synthesis of Complex Bioactive Molecules, contains 16 chapters, with particular emphasis given to organic, organometallic, and bio-oriented processes. The first part is directed toward the development of catalytic systems for CߝH functionalizations, cross-couplings, and reactions involving organometallic catalysts, organocatalysts, and bioorganic catalysts. The second part covers some of the most recent ASEP methods developed so far, such as domino reactions and rearrangements. The last two parts of the book are dedicated to the use of efficient tools for the synthesis of complex bioactives, in particular, carbohydrates and alkaloids, as well as to new techniques, such as the use of fluorous tags, flow chemistry, engineered biosynthesis, target- and diversity-oriented synthesis, and DNA-based asymmetric catalysis.

This book is an excellent source of inspiration for those planning the synthesis of complex molecules in the most efficient manner, for getting a hint on how to solve a specific synthetic problem, or simply for having fun discovering new chemistries and elaborating future chemical tools.

E. Negishi

Preface

In a world where atom-, step-, redox-, and pot-economy have become some of the most important challenges in synthetic organic chemistry, the development of innovative and synthetically useful tools has more than not transfigured the way chemists devise their syntheses of complex biologically active molecules. Thus, the idea behind this book was to emphasize the impact of modern synthetic tools on the synthesis of complex biologically active compounds, and show how they have provided new and elegant solutions to many synthetic puzzles. In this context, we decided to dedicate the first part of this book to modern catalysis with a special emphasis given to various key transformations such as C–H functionalizations (Chapter 1, S. Rousseaux, B. Liégault, and K. Fagnou), cross-couplings (Chapter 2, E. Colacino, J. Martinez, and F. Lamaty and Chapter 3, R. Marcia de Figueiredo, J.-M. Campagne, and D. Prim), gold-catalyzed reactions (Chapter 4, F. Gagosz), metathesis-based syntheses (Chapter 5, J.-A. Richard, S. Y. Ng, and D. Y.-K. Chen), and asymmetric organocatalysis (Chapter 6, M. Shoji and Y. Hayashi and Chapter 7, S. Shirakawa, S. A. Moteki, and K. Maruoka). The second part of the book provides a broad coverage of some of the most elegant and eco-compatible transformations developed so far, such as rearrangements (Chapter 8, J. Marco-Contelles and E. Soriano) and domino reactions (Chapter 9, L. F. Tietze, S. G. Stewart, and A. Düfert). The third part of the book is dedicated to the development of specific tools for the synthesis of carbohydrates (Chapter 12, X. Guinchard, S. Picard, and D. Crich) and alkaloids (Chapter 13, S. Bur and A. Padwa), while the fourth part unveils some of the most recent techniques, such as the use of fluorous tags (Chapter 10, W. Zhang), flow chemistry (Chapter 11, R. M. Myers, K. A. Roper, I. R. Baxendale, and S. V. Ley) and engineered biosynthesis (Chapter 14, C. J. B. Harvey and C. Khosla). Finally, the last two chapters of this book are dedicated to two prospective methods, namely, target- and diversity-oriented organic synthesis (Chapter 15, R. Rodriguez) and the use of DNA-based asymmetric catalysis (Chapter 16, M. Smietana, J.-J. Vasseur, J. Cossy, and S. Arseniyadis) that are particularly promising tools for the synthesis of complex bioactive molecules.

We would like to warmly thank all the authors for their enthusiasm, patience, professionalism, and most of all, their particularly didactic and detailed contributions. We also would like to thank the team at John Wiley & Sons, especially Anita Lekhwani, Sanchari Sil, and Angioline Loredo, for their helpful assistance during the entire preparation of this book.

Finally, we hope you will enjoy reading this book as much as we have enjoyed preparing it. We believe it will be a valuable source of information for both academic and industrial researchers, as well as to undergraduate and graduate students all over the world.

Janine Cossy and Stellios Arseniyadis

Contributors

Stellios Arseniyadis, Laboratoire de Chimie Organique, UMR 7084 CNRS ESPCI ParisTech, Paris, France

Ian R. Baxendale, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

Scott Bur, Department of Chemistry, Emory University, Atlanta, Georgia, USA

Jean Marc Campagne, Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-UM1-ENSCM, Ecole Nationale Supérieure de Chimie, Montpellier, France

David Y.-K. Chen, Department of Chemistry, Seoul National University, Seoul, South Korea

Evelina Colacino, Institut des Biomolécules Max Mousseron, Université Montpellier 2, Montpellier, France

Janine Cossy, Laboratoire de Chimie Organique, UMR 7084 CNRS ESPCI ParisTech, Paris, France

David Crich, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France

Renata Marcia de Figueiredo, Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-UM1-ENSCM, Ecole Nationale Supérieure de Chimie, Montpellier, France

Alexander Düfert, Institut für Organische und Biomolekulare Chemie, Universität Göttingen, Göttingen, Germany

Keith Fagnou, Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada

Fabien Gagosz, Laboratoire de Synthèse Organique, UMR 7652 CNRS Ecole Polytechnique, Palaiseau, France

Xavier Guinchard, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France

Colin J. B. Harvey, Department of Chemistry, Chemical Engineering, and Biochemistry, Stanford University, Stanford, California, USA

Yujiro Hayashi, Department of Industrial Chemistry, Tokyo University of Science, Tokyo, Japan

Chaitan Khosla, Department of Chemistry, Chemical Engineering, and Biochemistry, Stanford University, Stanford, California, USA

Frédéric Lamaty, Institut des Biomolécules Max Mousseron, Université Montpellier 2, Montpellier, France

Steven V. Ley, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

Benoît Liégault, Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada

José Marco-Contelles, Laboratorio de Química Médica y Computacional, Instituto de Química Orgánica General, Madrid, Spain

Jean Martinez, Institut des Biomolécules Max Mousseron, Université Montpellier 2, Montpellier, France

Keiji Maruoka, Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

Shin A. Moteki, Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

Rebecca M. Myers, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

Sin Yee Ng, Department of Chemistry, Seoul National University, Seoul, South Korea

Albert Padwa, Department of Chemistry, Emory University, Atlanta, Georgia, USA

Sébastien Picard, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France

Damien Prim, Université Versailles-St-Quentin-en-Yvelines, Institut Lavoisier de Versailles UMR CNRS 8180, Versailles, France

Jean-Alexandre Richard, Department of Chemistry, Seoul National University, Seoul, South Korea

Raphaël Rodriguez, Department of Chemistry, Cambridge University, Cambridge, United Kingdom

Kimberley A. Roper, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

Sophie Rousseaux, Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada

Seiji Shirakawa, Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

Mitsuru Shoji, Department of Industrial Chemistry, Tokyo University of Science, Tokyo, Japan

Michael Smietana, Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Université de Montpellier 1 et 2, Montpellier, France

Elena Soriano, Laboratorio de Química Médica y Computacional, Instituto de Química Orgánica General, Madrid, Spain

Scott G. Stewart, Institut für Organische und Biomolekulare Chemie, Universität Göttingen, Göttingen, Germany

Lutz F. Tietze, Institut für Organische und Biomolekulare Chemie, Universität Göttingen, Göttingen, Germany

Jean-Jacques Vasseur, Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Université de Montpellier 1 et 2, Montpellier, France

Wei Zhang, Department of Chemistry, University of Massachusetts, Boston, Massachusetts, USA

Chapter 1

C–H Functionalization: A New Strategy for the Synthesis of Biologically Active Natural Products

Sophie Rousseaux, Benoît Liégault, and Keith Fagnou

Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada

1.1 Introduction

The advent of transition metal-catalyzed transformations at C–H bonds has enabled the efficient formation of a wide range of carbon–carbon and carbon–heteroatom bonds from simple C–H bonds [1]. As a strategy, these transformations use unactivated C–H bonds as functional groups to generate molecular complexity. While these processes represent a chemical ideal from the standpoint of atom economy and synthetic efficiency, the ubiquitous nature of C–H bonds and their relative strength [2] pose a significant challenge for selectivity and reactivity, which has been the focus of research efforts over the past decade. The current knowledge in the field has enabled the use of C–H functionalization as a reliable tool for natural product synthesis, even as a late-stage manipulation in complex targets [3].

Synthetic approaches toward transition metal-catalyzed transformations at C–H bonds are divided between two distinct mechanisms [4]. Outer sphere mechanisms (coordination chemistry) proceed via the direct interaction of the C–H bond being functionalized with a ligand coordinated to the transition metal. This mechanism has been exploited both in metal-catalyzed carbene/nitrene insertions into C–H bonds and in metal-oxo-catalyzed C–H oxidations [5, 6]. On the other hand, inner sphere mechanisms (organometallic chemistry) involve the formation of a carbon–metal bond as a result of C–H bond cleavage [7]. This chapter will discuss the application of the latter form of reactivity, also known as C–H activation or C–H functionalization, to the synthesis of biologically active molecules. While many of the contributions made in the field will be highlighted, an exhaustive list of syntheses relying on this strategy will not be made. Instead, the examples described in the following sections have been chosen to give the reader a broad perspective of the different strategies of C–H bond functionalization that have been applied to natural product synthesis.

1.2 Palladium(0)-Catalyzed Intramolecular Direct Arylation

Direct arylation constitutes an important alternative to traditional cross-coupling reactions for the formation of biaryl bonds [8], a prevalent motif in biologically active and medicinally relevant molecules. In direct arylation reactions, one of the preactivated coupling partners, often the organometallic component, is replaced by a simple (hetero)arene C–H bond, streamlining the overall biaryl bond forming process (Scheme 1.1a) [9]. Several transition metals have been used to harness this reactivity, including ruthenium, rhodium, palladium, and copper to name a few. Pd(0)-based catalyst systems have been extensively investigated in this area due to their functional group tolerance. Moreover, they provide the ability to use commercially available (or easily prepared) aryl halides as the sole preactivated coupling partner in these processes.

Scheme 1.1 Palladium(0)-catalyzed direct arylation.

The general catalytic cycle for this transformation consists of three steps (Scheme 1.1b): (i) oxidative addition of the aryl (pseudo)halide to a Pd(0) catalyst generates a Pd(II) intermediate, (ii) interaction of the Pd(II) species with the (hetero)arene C–H bond leads to C–H bond cleavage and elimination of HX, and (iii) reductive elimination produces the biaryl product while regenerating the Pd(0) catalyst.

The selective functionalization of an sp2 C–H bond in (hetero)arenes containing several potential reaction sites poses a significant challenge to direct arylation reactions. When the electronic and/or steric properties of the substrate do not lead to regioselective C–H bond cleavage, strategies have been developed to overcome this hurdle. The installation of a Lewis basic directing group on the unactivated coupling partner, which acts as a ligand for the metal, can be used to guide site-specific arene metalation [10]. On the other hand, intramolecular reactions also eliminate some of the problems of regioselectivity. In these cases, C–H bond functionalization is generally governed by the size of the metalacyclic intermediate formed during the catalytic cycle.

The mechanism of C–H bond cleavage in these processes has been extensively debated in the literature, with two pathways having received significant attention. In direct arylation reactions featuring electron-rich (hetero)aromatic substrates, an electrophilic aromatic substitution (SEAr) mechanism is typically proposed involving a Friedel–Crafts process, where the nucleophilic (hetero)arene reacts with the electrophilic metal center (Scheme 1.2a) [11]. On the other hand, electron-deficient and electron-neutral arenes have been proposed to react through a concerted metalation–deprotonation (CMD) mechanism, involving C–H deprotonation with concomitant (hetero)arene metalation () [12]. It should also be noted that recent studies have demonstrated that this CMD pathway may also be operative in direct arylation reactions featuring electron-rich arenes [13].