Cover; Contents; Section 1: Synthetic Approaches to Enable Small-molecule Probe Discovery; Chapter 1 Synthetic Tools for the Elucidation of Biological Mechanisms; 1.1 Context; 1.2 Synthetic Approaches to Enable Small-molecule Probe Discovery; 1.3 Synthetic Approaches to Classes of Modified Biomolecule; 1.4 Summary; References; Chapter 2 The Application of Diversity-oriented Synthesis in Chemical Biology; 2.1 Introduction; 2.1.1 Small Molecule Screening Collections; 2.1.2 Sources of Complex and Diverse Libraries
2.1.3 Synthetic Strategies for the Construction of Complex and Diverse Libraries: Diversity-oriented Synthesis2.2 Application of Diversity-oriented Synthesis for the Identification of Small Molecule Modulators; 2.2.1 Structural Diversity and Phenotypic Screening; 2.2.2 The Role of DOS in Target Validationthrough the Discovery of New Chemical Probes; 2.3 Conclusions and Outlook; Acknowledgements; References; Chapter 3 Biology-oriented Synthesis; 3.1 Introduction; 3.2 Structural Classification of Natural Products, Protein Structure Similarity Clustering and Scaffold Hunter
3.3 Implications and Opportunities for Biology-oriented Synthesis3.4 Applications of Biology-oriented Synthesis; 3.4.1 Chemical-structure-and Bioactivity-guided Approaches; 3.4.2 Protein-structure-clustering-guided Approaches; 3.4.3 Natural-product-derived-fragment-based Approaches; 3.5 Conclusions and Outlook; References; Chapter 4 Lead- and Fragment-oriented Synthesis; 4.1 Introduction; 4.1.1 Introduction to Lead-oriented Synthesis; 4.1.2 Introduction to Fragment-oriented Synthesis; 4.2 Lead-oriented Synthesis; 4.2.1 Diverse and Novel Scaffolds for Lead-oriented Synthesis
4.2.2 New Synthetic Methods for Lead-oriented Synthesis4.2.3 Natural Products as Inspiration for Lead-like Libraries; 4.2.4 The European Lead Factory; 4.3 Fragment-oriented Synthesis; 4.4 Conclusions; References; Chapter 5 Principles and Applications of Fragment-based Drug Discovery for Chemical Probes; 5.1 Introduction; 5.1.1 What Is a Chemical Probe?; 5.1.2 Chemical Probe Characteristics; 5.1.3 Fragment Library Design; 5.1.4 Screening Methods/Fragment Elaboration; 5.2 Case Studies; 5.2.1 A-1155463 (BCL-XL); 5.2.2 CCT244747 (CHK1); 5.2.3 GSK2334470 (PDK1); 5.2.4 PFI-3 (SMARCA2/4 and PB1)
5.2.5 BI-9564 (BRD9)5.2.6 Astex DDR1 Kinase Inhibitor (DDR1/DDR2); 5.3 Outlook; Abbreviations; References; Chapter 6 Function-driven Discovery of Bioactive Small Molecules; 6.1 Context; 6.1.1 Chemical Approaches That Underpin Bioactive Small-molecule Discovery; 6.1.2 Evolution of Biosynthetic Pathways to Natural Products; 6.1.3 Scope of This Chapter; 6.2 Synthetic Fermentation; 6.2.1 Discovery of a Protease Inhibitor; 6.2.2 Conclusion; 6.3 Activity-directed Synthesis; 6.3.1 Discovery of Androgen Receptor Agonists Using Intramolecular Reactions
0
8
8
8
8
An ideal guide for postgraduate students and researchers in synthetic organic chemistry and chemical biology, Chemical and Biological Synthesis introduces synthetic techniques and methods to those who wish to incorporate synthesis for the first time in their biology-focused research programmes.