New Tide of Natural Product Chemistry

Description

The book consists of seventeen chapters covering novel bioactive natural products, uncovering life phenomena with natural products, biosynthesis of natural products, total synthesis of complex natural products by innovative strategies, and drug discovery using natural products. Each chapter begins with a brief and easy-to-understand introduction, then presents the cutting-edge research in each individual specialty. Cover Half Title New Tide of Natural Product Chemistry Copyright Introduction Contents Part I: Exploring Novel Bioactive Natural Products and Uncovering Life Phenomena with Natural Products 1. Synthetic Biology-Based Natural Product Discovery 1.1 Introduction 1.2 Diterpenoid Pyrones (DDPs) with a Decalin Skeleton Produced by Filamentous Fungi 1.3 Reconstruction of Natural DDP Biosynthetic Pathways and Discovery of Naturally Programmed DDPs 1.4 Discovery of DDPs not Programmed in Nature by Redesign of the DDP Biosynthetic Pathways 1.5 Evaluation of Biological Activities of the DDPs 1.6 Conclusion References 2. Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Inhibitors Isolated from Subtropical Marine Cyanobacteria in Japan 2.1 Introduction 2.2 Iezoside 2.3 Kurahyne 2.4 Biselyngbyasides and Their Aglycons, Biselyngbyolides 2.5 Possible Ecological Role of SERCA Inhibitors Produced by Marine Cyanobacteria 2.6 Conclusion References 3. Marine Natural Products Targeting Tumor Microenvironment 3.1 Introduction 3.2 Screening of Hypoxia-Selective Growth Inhibitors 3.2.1 Bioactivity and Action Mechanism of Furospinosulin-1 3.2.2 Synthesis and Evaluation of Affinity Probe of Furospinosulin-1 3.2.3 Target Identification of Furospinosulin-1 3.2.4 Structure Confirmation of Dictyoceratins-A and -C by Total Synthesis 3.2.5 SAR and Target Identification of Dictyoceratin-C 3.3 Search for Selective Growth Inhibitors Under Glucose-Starved Condition 3.3.1 Structure Elucidation of Biakamides A-D by NMR and Total Synthesis 3.3.2 Bioactivity and SAR of Biakamides 3.4 Conclusion References 4. Chemical Biology Studies on Aplyronine A, A PPI-Inducing Antitumor Macrolide from Sea Hare 4.1 Introduction 4.2 Biochemical Evaluations of ApA 4.3 Binding Mode of Actin–ApA–Tubulin HTC Revealed by MD Simulation 4.4 Synthesis and Biological Activities of ApA Analogs 4.5 Molecular Modeling Studies of ApA and Its Side-Chain Analogs 4.6 Development of Versatile Actin-Affinity Tags Designed from the ApA Side-Chain Part 4.7 Conclusion References 5. Chemical Synthesis and Immunological Functions of Bacterial Lipid A for Vaccine Adjuvant Development and Bacterial-Host Chemical Ecology Research 5.1 Introduction 5.2 Bacterial Glycolipid Lipid A, an Innate Immune Stimulator 5.3 Practical Synthetic and Semi-Synthetic Lipid A Adjuvants 5.4 Lipid A Adjuvant Development Based on Bacterial-Host Chemical Ecology 5.4.1 Lipid A Mediates Bacterial-Host Chemical Ecology 5.4.2 Parasitic Bacterial Lipid A 5.4.3 Symbiotic Bacterial Lipid A 5.4.4 Lipid A in Fermented Foods as Adjuvants 5.5 Conclusion References Part II: Uncovering Biosynthesis of Natural Products 6. Dissecting Biosynthesis of Natural Products Toward Drug Discovery 6.1 Introduction 6.2 Aspirochlorine Biosynthesis 6.3 Fumagillin Biosynthesis 6.4 Pseurotin/Synerazol Biosynthesis 6.5 Closing Remarks References 7. A New Trend in Biosynthetic Studies of Natural Products: The Bridge Between the Amino Acid Sequence Data and the Chemical Structure 7.1 Introduction 7.2 Fungal Polyketide Synthases 7.2.1 Classification of Fungal Polyketide Synthases 7.2.2 General Polyketide Chain Elongation Mechanism 7.3 Phylogenetic Analysis of Hybrid-PKSs to Predict the Chemical Space of Hybrid-PKs 7.4 Focused Functional Analysis of HR-PKSs Using the Aspergillus Oryzae Expression System 7.5 Unified Stereochemical Rule of Fungal PKSs 7.5.1 Stereochemical Course to Synthesize the Backbone Structure of Polyhydroxy PKs Classified into PMA Clades 7.5.2 Proposal of a Unified Stereochemical Rule 7.6 Conclusion and Perspectives References 8. Biosynthesis of β-Amino Acid-Containing Macrolactam Polyketides 8.1 Introduction 8.2 3-Aminoisobutyric Acid Unit-Containing Macrolactams Such as Vicenistatin 8.2.1 Chemical Structures and Biological Activities of 3-Aminoisobutyric Acid Unit-Containing Macrolactams 8.2.2 Vicenistatin Biosynthesis 8.2.3 Structural Analysis of Vicenistatin Biosynthetic Enzymes 8.2.4 Production of Vicenistatin Derivative 8.3 β-Alanine Unit-Containing Macrolactams Such as Fluvirucin B2 8.3.1 Chemical Structures and Biological Activities of Fluvirucins 8.3.2 Fluvirucin Biosynthesis 8.4 3-Aminobutyric Acid Unit-Containing Macrolactams Such as Incednine 8.4.1 Chemical Structures and Biological Activities of 3-Aminobutyric Acid Unit-Containing Macrolactams 8.4.2 Incednine Biosynthesis 8.4.3 Structural Analysis of Incednine Biosynthetic Enzymes 8.4.4 Production of Incednine Derivatives 8.5 β-Phenylalanine Unit-Containing Macrolactams Such as Hitachimycin 8.5.1 Chemical Structures and Biological Activities of β-Phenylalanine Unit-Containing Macrolactams 8.5.2 Hitachimycin Biosynthesis 8.5.3 Structural Analysis of HitB 8.5.4 Production of Hitachimycin Derivatives 8.6 3-Aminofatty Acid Unit-Containing Macrolactams Such as Cremimycin 8.6.1 Chemical Structures and Biological Activities of 3-Aminofatty Acid Unit-Containing Macrolactams 8.6.2 Cremimycin Biosynthesis 8.6.3 Structural Analysis of CmiS6 8.7 Conclusions and Future Perspectives References Part III: Total Synthesis of Complex Natural Products by Innovative Strategies 9. Synthetic Approach Toward Structural Elucidation of Marine Natural Product Symbiodinolide 9.1 Introduction 9.2 Synthesis and Absolute Configuration of the C1′–C25′ Fragment 9.3 Synthesis and Relative Configuration of the C1–C13 Fragment 9.4 Synthesis and Absolute Configuration of the C14–C24 Fragment 9.5 Synthesis and Absolute Configuration of the C23–C34 Fragment 9.6 Synthesis and Absolute Configuration of the C33–C42 Fragment 9.7 Synthesis and Relative Configuration of the C79–C104 Fragment 9.7.1 Synthesis of the Proposed C79–C104 Fragment 9.7.2 Strategy for the Stereostructural Elucidation 9.7.3 Synthesis and Relative Configuration of the C79–C97 Fragment 9.7.4 Synthesis and Relative Configuration of the C94–C104 Fragment 9.7.5 Stereochemical Revision of the C79–C104 Fragment 9.8 Conclusion References 10. Collective Synthesis of Monoterpenoid Indole Alkaloids Using Bioinspired Strategies 10.1 Introduction 10.2 Biosynthesis of Monoterpenoid Indole Alkaloids 10.3 Asymmetric Total Synthesis of Secologanin 10.4 Development of Diastereoselective Pictet–Spengler Reaction, and Total Synthesis of Strictosidine 10.5 Bioinspired Total Syntheses of Strictosamide, Neonaucleoside A, and Cymoside 10.6 Synthetic Strategies for Monoterpenoid Indole Alkaloids Produced in the Early Stages of Biosynthesis, and Synthesis of Secologanin Aglycone Silyl Ether 10.7 Bioinspired Transformations to Nacycline, Cathenamine, and Tetrahydroalstonine from Strictosidine Aglycone 10.8 Bioinspired Transformations to Corynantheine-Type Indole Alkaloids 10.9 Bioinspired Transformations to Akagerine-Related Indole Alkaloids 10.10 Bioinspired Transformations to Naucleaoral-Related Indole Alkaloids 10.11 Conclusion References 11. Total Syntheses of Bioactive Oxacyclic Natural Products 11.1 Introduction 11.2 Lysidicin A 11.3 Amphirionin-4 11.4 Anthecularin 11.5 Celafolins B-1, B-2, B-3 11.6 Conclusion References 12. Total Syntheses of Densely Oxygenated Natural Products by Radical-Based Decarbonylative Convergent Assembly 12.1 Introduction 12.2 Design of Radical-Based Convergent Strategies for the Synthesis of Highly Oxygenated Natural Products 12.3 Total Synthesis of Manzacidin A 12.4 Unified Total Synthesis of Polyoxins 12.5 Total Synthesis of Hikizimycin 12.6 Summary and Perspective References 13. Nucleophilic Addition to Amides Toward Efficient Total Synthesis of Complex Alkaloids 13.1 Nucleophilic Addition to Amides 13.2 Total Synthesis of Gephyrotoxin 13.2.1 Gephyrotoxin 13.2.2 Chemoselective Reductive Nucleophilic Addition to N-Methoxyamides 13.2.3 Total Synthesis of Gephyrotoxin 13.3 Unified Total Synthesis of Stemoamide-Type Alkaloids 13.3.1 Stemoamide-Type Alkaloids and Their Synthetic Plan 13.3.2 Iridium-Catalyzed Reductive Nucleophilic Addition to Tertiary Amides 13.3.3 Unified Total Synthesis of Stemoamide-Type Alkaloids 13.4 Conclusions References 14. Equilibrium-Controlled Stereoselective Sequential Cyclizations Enabled Concise Total Synthesis of Complex Indole Alkaloid, Tronocarpine 14.1 Introduction 14.2 Tronocarpine 14.3 First Total Synthesis of (+)-Tronocarpine by Hans and Coworkers 14.4 Synthetic Design for the Construction of the Azabicyclo[3.3.1]nonane Core by Equilibrium-Controlled Stereoselective Tandem Cyclization 14.5 Concise Total Synthesis of (Rac)-Tronocarpine 14.6 Attempts to Obtain an Optical Tronocarpine 14.7 Conclusion and Perspective References Part IV: New Approach for Drug Discovery Using Natural Products 15. High-Throughput Searches for Natural Products as Aggregation Modulators of Amyloidogenic Proteins 15.1 Aggregation of Amyloidogenic Proteins and Neurodegeneration 15.2 Fluorescent Probes of Amyloid Aggregates 15.3 HTS of Natural Products That Modulate Amyloid Aggregation 15.4 Searching for Natural Products That Delay the Nucleation Phase and Promote the Elongation Phase of Aβ Aggregation 15.5 Differential Activity Searching for Aβ Aggregation Inhibitors Using LC–MS Combined with Principal Component Analysis (PCA) 15.6 Inhibitory Mechanism of Aβ Aggregation by Natural Products 15.7 Conclusions and Future Perspectives References 16. Discovery of Natural Product Analogues with Altered Activities by a High-Throughput Strategy 16.1 Introduction 16.2 Lysocin E 16.3 Strategy Design for Discovering More Potent Analogues of Lysocin E 16.4 Construction of a Lysocin E-Based Library 16.5 Discovery of Lysocin E Analogues Showing Enhanced Antibacterial Activity 16.6 Gramicidin A 16.7 Strategy Design for Discovering Gramicidin A Analogues with Altered Activity Profiles 16.8 Construction of the Gramicidin A-Based Library 16.9 Discovery of Gramicidin A Analogues That Exhibit Altered Activities 16.10 Conclusion References 17. Development of Novel Ligands That Modulate Innate-Like T Cells 17.1 Introduction 17.2 Development of Novel NKT Cell Modulators 17.2.1 Background of NKT Cells 17.2.2 Ligand Design of Amide-Containing α-GalCer Analogues 17.2.3 Synthesis of α-GalCer Analogues 17.2.4 Evaluation of α-GalCer Analogues 17.2.5 MD Simulation of Complexes with mCD1d and α-GalCer Analogues 17.2.6 Design of Th2 Selective Ligands 17.2.7 Summary of the Development of Novel NKT Cell Modulators 17.3 SAR Studies of MAIT Cell Modulators 17.3.1 Background of MAIT Cells 17.3.2 Concept of SAR Studies 17.3.3 Synthesis of 5-OP-RU Analogues 17.3.4 Evaluation of 5-OP-RU Analogues 17.3.5 Binding Mode Analysis of 5-OP-RU Analogues 17.3.6 Summary of SAR Studies on 5-OP-RU Analogues 17.4 Conclusion References