Linker Strategies in Solid-Phase Organic Synthesis

Linker design is an expanding field with an exciting future in
state-of-the-art organic synthesis. Ever-increasing numbers of
ambitious solution phase reactions are being adapted for
solid-phase organic chemistry and to accommodate them, large
numbers of sophisticated linker units have been developed and are
now routinely employed in solid-phase synthesis.

Linker Strategies in Solid-Phase Organic Synthesis guides
the reader through the evolution of linker units from their genesis
in solid-supported peptide chemistry to the cutting edge diversity
linker units that are defining a new era of solid phase
synthesis. Individual linker classes are covered in easy to
follow chapters written by international experts in their
respective fields and offer a comprehensive guide to linker
technology whilst simultaneously serving as a handbook of synthetic
transformations now possible on solid supports. Topics include:

• the principles of solid phase organic synthesis

• electrophile and nucleophile cleavable linker units

• cyclative cleavage as a solid phase strategy

• photocleavable linker units

• safety-catch linker units

• enzyme cleavable linker units

• T1 and T2 -versatile triazene linker groups

• hydrazone linker units

• benzotriazole linker units

• phosphorus linker units

• sulfur linker units

• selenium and tellurium linker units

• sulfur, oxygen and selenium linker units cleaved by radical
  processes

• silicon and germanium linker units

• boron and stannane linker units

• bismuth linker units

• transition metal carbonyl linker units

• linkers releasing olefins or cycloolefins by ring-closing
  metathesis

• fluorous linker units

• solid-phase radiochemistry

The book concludes with extensive linker selection tables,
cataloguing the linker units described in this book according to
the substrate liberated upon cleavage and conditions used to
achieve such cleavage, enabling readers to choose the right linker
unit for their synthesis.

Linker Strategies in Solid-Phase Organic Synthesis is an
essential guide to the diversity of linker units for organic
chemists in academia and industry working in the broad areas of
solid-phase organic synthesis and diversity oriented synthesis,
medicinal chemists in the pharmaceutical industry who routinely
employ solid-phase chemistry in the drug discovery business, and
advanced undergraduates, postgraduates, and organic chemists with
an interest in leading-edge developments in their field.

Auteur

Dr Peter J. H. Scott, Department of Radiology, University of Michigan, Ann Arbor, USA
Dr. Peter Scott has worked at Siemens Molecular Imaging and Biomarker Research where he was head of radiochemistry at the LA Tech Center and involved in the design and synthesis of novel radiopharmaceuticals for use in PET imaging. In April 2009 Dr. Scott joined the University of Michigan in the Department of Radiology where his research interests are developing novel tracers and technology for PET imaging, including solid phase radiochemistry.

Résumé
Linker design is an expanding field with an exciting future in state-of-the-art organic synthesis. Ever-increasing numbers of ambitious solution phase reactions are being adapted for solid-phase organic chemistry and to accommodate them, large numbers of sophisticated linker units have been developed and are now routinely employed in solid-phase synthesis. Linker Strategies in Solid-Phase Organic Synthesis guides the reader through the evolution of linker units from their genesis in solid-supported peptide chemistry to the cutting edge diversity linker units that are defining a new era of solid phase synthesis. Individual linker classes are covered in easy to follow chapters written by international experts in their respective fields and offer a comprehensive guide to linker technology whilst simultaneously serving as a handbook of synthetic transformations now possible on solid supports. Topics include:

• the principles of solid phase organic synthesis
• electrophile and nucleophile cleavable linker units
• cyclative cleavage as a solid phase strategy
• photocleavable linker units
• safety-catch linker units
• enzyme cleavable linker units
• T1 and T2 versatile triazene linker groups
• hydrazone linker units
• benzotriazole linker units
• phosphorus linker units
• sulfur linker units
• selenium and tellurium linker units
• sulfur, oxygen and selenium linker units cleaved by radical processes
• silicon and germanium linker units
• boron and stannane linker units
• bismuth linker units
• transition metal carbonyl linker units
• linkers releasing olefins or cycloolefins by ring-closing metathesis
• fluorous linker units
• solid-phase radiochemistry
  The book concludes with extensive linker selection tables, cataloguing the linker units described in this book according to the substrate liberated upon cleavage and conditions used to achieve such cleavage, enabling readers to choose the right linker unit for their synthesis.

Linker Strategies in Solid-Phase Organic Synthesis is an essential guide to the diversity of linker units for organic chemists in academia and industry working in the broad areas of solid-phase organic synthesis and diversity oriented synthesis, medicinal chemists in the pharmaceutical industry who routinely employ solid-phase chemistry in the drug discovery business, and advanced undergraduates, postgraduates, and organic chemists with an interest in leading-edge developments in their field.

Contenu
Foreword. Preface.

List of Contributors.

About the Editor.

Abbreviations.

I: INTRODUCTION.

Chapter 1: General Introduction (Scott L. Dax).

1.1 Introduction, Background and Pivotal Discoveries.

1.2 Fundamentals of Conducting Solid-Phase Organic Chemistry.

1.3 Concluding Comments.

1.4 Personal Perspective and Testimony: Solid-phase Mannich Chemistry.

1.5 References.

II: TRADITIONAL LINKER UNITS FOR SOLID-PHASE ORGANIC SYNTHESIS.

Chapter 2: Electrophile Cleavable Linker Units (Michio Kuruso).

2.1 Introduction.

2.2 Resins for use with Electrophilic Linkers.

2.3 Electrophile Cleavable Linkers.

2.4 Conclusion.

References.

Chapter 3: Nucleophile Cleavable Linker Units (Andrea Porcheddu and Giampaolo Giacomelli).

3.1 Introduction.

3.2 Linker Units.

3.3 Nucleophilic Labile Linker Units.

3.4 Conclusion.

References.

Chapter 4: Cyclative Cleavage as a Solid-Phase Strategy (A. Ganesan).

4.1 Introduction.

4.2 C-N bond formation.

4.3 C-O bond formation.

4.4 C-C bond formation.

4.5 Conclusion.

References.

Chapter 5: Photolabile Linker Units (Christian Bochet and Sébastien Mercier).

5.1 Introduction.

5.2 Linkers Based on the Ortho-Nitrobenzyloxy Function.

5.3 Linkers Based on the Ortho-Nitrobenzylamino Function.

5.4 Linkers Based on the Substituted Ortho-Nitrobenzyl Group.

5.5 Linkers Based on the Ortho-Nitroveratryl Group.

5.6 Linkers Based on the Phenacyl Group.

5.7 Linkers Based on the Para-Methoxyphenacyl Group.

5.8 Linkers Based on the Benzoin Group.

5.9 Linkers Based on the Pivaloyl Group.

5.10 Traceless Linkers.

5.11 Other Types of Photolabile Linker Units.

5.12 Conclusion.

References.

Chapter 6: Safety-Catch Linker Units (Sylvain Lebreton and Marcel Pátek).

6.1 Introduction.

6.2 Activation of a carbonyl group by the inductive effect (I-) of an adjacent substituent.

6.3 Activation by the mesomeric effect (M-) of the XY=Z moiety adjacent to a carbonyl group.

6.4 Activation by the positive mesomeric effect (M+) of the -X-Y=Z moiety adjacent to a N-acyl or O-alkyl group.

…