MODERN TOOLS FOR THE SYNTHESIS OF COMPLEX BIOACTIVE MOLECULES -- CONTENTS -- 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 -- 2.2.1. Synthesis of Polyenes -- 2.2.2. Synthesis of Amino Acids and Macrocyclic Peptides -- 2.2.3. Synthesis of Macrocycles -- 2.2.4. Synthesis of Small Heterocycles -- 2.3. LARGE-SCALE SYNTHESIS OF BIOLOGICALLY ACTIVE MOLECULES -- 2.3.1. Nonsteroidal Ligand A-224817.0 1A -- 2.3.2. Phosphodiesterase Inhibitor PDE472 -- 2.3.3. Reverse Transcriptase Inhibitor MIV-150 -- 2.3.4. B-Raf Kinase Inhibitors -- 2.3.5. mGluR1 Antagonist -- 2.4. CONCLUSION -- REFERENCES -- CHAPTER 3: METAL-CATALYZED C-HETEROATOM CROSS-COUPLING REACTIONS -- 3.1. GENERAL INTRODUCTION -- 3.2. BUCHWALD-HARTWIG-TYPE REACTIONS -- 3.2.1. Introduction -- 3.2.2. Mechanism -- 3.2.3. Scope and Limitations.

3.2.4. Applications in the Synthesis of Complex Bioactive Molecules -- 3.2.5. C-N Bond Formation -- 3.2.6. C-S and C-O Bond Formation -- 3.3. ULLMANN-TYPE REACTIONS -- 3.3.1. Introduction -- 3.3.2. Mechanism -- 3.3.3. Scope and Limitations -- 3.3.4. Applications in the Synthesis of Complex Bioactive Molecules -- 3.3.5. C-N Bond Formation -- 3.3.6. C-O Bond Formation -- 3.4. MISCELLANEOUS -- 3.4.1. Chan-Lam-Evans -- 3.4.2. Iron/Copper-Mediated Methodologies -- 3.4.3. Other Metals -- 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 -- 4.2.1. Cyclizations Leading to Furan and Pyran Derivatives -- 4.2.2. Spiroketalizations -- 4.2.3. Other Transformations -- 4.3. GOLD-CATALYZED FORMATION OF NITROGEN-CONTAINING HETEROCYCLES -- 4.3.1. Cyclizations Involving the Formation of a New C-N Bond -- 4.3.2. Cyclizations Involving the Formation of a New C-C Bond -- 4.4. GOLD-CATALYZED FORMATION OF CARBOCYCLES -- 4.4.1. Cyclizations Involving the Formation of a Single New C-C Bond -- 4.4.2. Cyclizations Involving the Formation of Several New C-C Bonds -- 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 -- 6.2.1. Direct Aldol Reaction -- 6.2.2. Mannich Reaction.

6.2.3. Michael Reaction -- 6.2.4. Diels-Alder Reaction -- 6.2.5. Pictet-Spengler Reaction -- 6.2.6. SOMO Reaction -- 6.3. HETEROATOM INSTALLATION -- 6.3.1. Epoxidation of Alkene -- 6.3.2. α-Aminoxylation -- 6.3.3. α-Amination -- 6.4. CASCADE REACTION -- 6.5. CONCLUSION -- REFERENCES -- CHAPTER 7: ASYMMETRIC PHASE-TRANSFER CATALYSIS -- 7.1. INTRODUCTION -- 7.2. ALKYLATION -- 7.2.1. Asymmetric Synthesis of α-Alkyl α-Amino Acids -- 7.2.2. Asymmetric Synthesis of α,α-Dialkyl α-Amino Acids -- 7.2.3. Alkylation of Peptides -- 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 -- 8.2.1. The Cope Rearrangement -- 8.2.2. The Oxy-Cope Rearrangement -- 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. THEMEYER-SCHUSTERANDRUPEREARRANGEMENTS -- 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 -- 9.3.1. Domino Reactions with Michael Additions as the Initiating Step -- 9.3.2. Domino Reactions with Aldol Reactions as the Initiating Step -- 9.3.3. Nucleophilic Substitutions, 1,2-Additions, or Other Reactions as the Initiating Step -- 9.4. RADICAL DOMINO REACTIONS -- 9.5. PERICYCLIC REACTIONS -- 9.6. PHOTOCHEMICALLY INDUCED DOMINO REACTIONS -- 9.7. TRANSITION METAL-CATALYZED DOMINO REACTIONS -- 9.7.1. Pd-Catalyzed Domino Reactions -- 9.7.2. Rhodium-Catalyzed Domino Reactions.

9.7.3. Ruthenium-Catalyzed Domino Reactions Applying Metatheses -- 9.8. OXIDATIVE OR REDUCTIVE DOMINO REACTIONS -- 9.8.1. Domino Reactions Initiated by Oxidation -- 9.8.2. Domino Reactions Initiated by Reduction -- 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 -- 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 -- 11.4.1. Butane-2, 3-Diacetal-Protected Diols -- 11.4.2. Yne-Ones and Pyrazoles as Primary Building Blocks -- 11.4.3. Curtius Rearrangement -- 11.4.4. Fluorination Reactions -- 11.4.5. Seyferth-Gilbert Homologation Using the Bestmann- Ohira Reagent for the Formation of Acetylenes and Triazoles -- 11.4.6. 3-Nitropyrrolidine Building Blocks -- 11.4.7. 4,5-Disubstituted Oxazoles as Building Blocks -- 11.5. MULTISTEP FLOW SYNTHESIS OF NATURAL PRODUCTS AND PHARMACEUTICAL COMPOUNDS -- 11.5.1. Casein Kinase I Inhibitors -- 11.5.2. A Quinolone 5HT1B Antagonist -- 11.5.3. Imatinib Mesylate -- 11.6. CONCLUSION -- REFERENCES -- CHAPTER 12: SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES -- 12.1. INTRODUCTION -- 12.1.1. Heparin Pentasaccharide Synthesis -- 12.1.2. Moenomycin Pentasaccharide Synthesis -- 12.2. 1,2-cis-EQUATORIAL GLYCOSIDES -- 12.2.1. β-Mannopyranosides.

12.2.2. β-Rhamnopyranosides -- 12.3. 1,2-trans-EQUATORIAL LINKAGES -- 12.3.1. The Globo-H Polysaccharide -- 12.3.2. Nitrile Effect -- 12.3.3. 1,2-Anhydro Sugars -- 12.3.4. Preactivation of Thioglycosides -- 12.3.5. Programmable Reactivity-Based One-Pot Strategy -- 12.3.6. Solid-Phase Synthesis of Globo-H -- 12.4. 1,2-cis-AXIAL GLYCOSIDES -- 12.4.1. Armed Galactosyl Donors -- 12.4.2. Conformational Constraint by a 4,6-O-Acetal -- 12.4.3. Boons' Participation Method -- 12.5. α-SIALIC ACID GLYCOSIDES -- 12.5.1. Synthesis of α-Sialyl Derivatives and Gangliosides -- 12.5.2. Synthesis of N-Glycolylneuraminic Acid and KDNContaining Oligosaccharides -- 12.6. URONIC ACID GLYCOSIDES -- 12.7. β-ARABINOFURANOSIDES -- 12.7.1. Cyclically Constrained Donors -- 12.7.2. β-Selective Donors with Acyclic Protecting Groups -- 12.7.3. Intramolecular Aglycon Delivery -- 12.7.4. Synthesis of Sucrose -- 12.8. CONCLUSION -- REFERENCES -- CHAPTER 13: AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS -- 13.1. INTRODUCTION -- 13.2. AMMONIUM 1,3-YLIDES -- 13.2.1. Isomünchnones as Dipoles -- 13.2.2. Isothiomünchnones as Dipoles -- 13.2.3. Cross-Conjugated Heteroaromatic Betaines -- 13.2.4. Push-Pull Dipoles -- 13.2.5. Intermolecular Azomethine Ylide Cycloadditions -- 13.2.6. Intramolecular Azomethine Ylide Cycloadditions -- 13.2.7. Other Strategies -- 13.3. 1,2-AMMONIUM YLIDES -- 13.3.1. [1,2]-Rearrangements (the Stevens Rearrangement) -- 13.3.2. [2,3]-Rearrangements -- 13.4. CONCLUSION -- REFERENCES -- CHAPTER 14: PRECURSOR-DIRECTED BIOSYNTHESIS OF POLYKETIDE AND NONRIBOSOMAL PEPTIDE NATURAL PRODUCTS -- 14.1. INTRODUCTION -- 14.2. NATURAL PRODUCT BIOSYNTHESIS -- 14.2.1. Polyketide Biosynthesis -- 14.2.2. Nonribosomal Peptide Biosynthesis -- 14.3. PRECURSOR-DIRECTED BIOSYNTHESIS -- 14.3.1. Introduction -- 14.3.2. Precursor Complexity and Enzyme Tolerance.

14.3.3. Host Selection and Biosynthetic System Engineering.