Medicinal chemistry of bioactive natural products / edited by Xiao-Tian Liang, Wei-Shuo Fang.

Includes bibliographical references and index.

Chapter 1 The Chemistry and Biology of Epothilones?Lead Structures for the Discovery of Improved Microtubule inhibitors
Karl-Heinz Altmann
1. Introduction
2. Biological effects of Epo B
In vitro activity
In vivo antitumor activity
3. Epothilone analogs and SAR studies
Lactam-based analogs
Modifications in th eC9-C11 regions
Modifications of the epoxide moiety
C-26 modifications
Aza-epothilones
4. Pharmacophore modelling and conformational studies
5. Epothilone analogs in clinical development
6. Conclusions
7. Acknowledgement
8. References
Chapter 2 The Chemistry and Biology of Vancomycin and Other Glycopeptide Antibiotic Derivatives
Roderich D. Suessmuth
1. Introduction
2. Classification of Glycopeptide Antibiotics
3. Mode of Action
4. Glycopeptide resistance
5. Biosynthesis
6. Total synthesis
7. Glycopeptides as Chiral Selectors in Chromatography and Capillary Electrophoresis
8. Structural Modifications of Glycopeptide Antibiotics and Structure Activity Relationship (SAR) Studies
8.1 Modifications of Glycopeptide Antibiotics
8.2 Rational Concepts for the Design of Novel Glycopeptides
8.3 Conclusions
9. References

Chapter 3 Structure Modifications and Their Influences on Antitumor and Other Related Activities of Taxol and Its Analogues
Wei-shuo Fang, Qi-Cheng Fang, Xiao-tian Liang
1. Discovery and research and development of Taxol?
2. Paclitaxel analogues active against sensitive tumor cells
2.1 C-13 side chain
2.2 A ring and its substitutions
2.3 B ring and its substitutions
2.4 C ring and its substitutions
2.5 D ring
2.6 Macrocyclic analogues
2.7 Miscellaneous
3. Exploration on mechanism of paclitaxel related to tubulin binding and quest for its pharmacophore
3.1 Biochemical mechanism of paclitaxel related to tubulin binding
3.2 Identification of bioactive conformations and quest for a pharmacophore for paclitaxel
4. Natural taxanes and semi-synthetic taxoids overcoming multi-drug resistance (MDR)
4.1 Structure modified taxoids with better activity towards MDR tumors
4.2 Non-paclitaxel type taxoids with MDR reversal activities
4.3 Factors contributing to the resistance to paclitaxel
5 Design, synthesis and pharmacological activity of prodrugs of paclitaxel
5.1 Prodrugs prepared to improve water solubility
5.2 Prodrugs designed for enhancing specificity
6. Other biological actions of paclitaxel--Apoptosis and immune stimulation
7. New anti-microtubule molecules mimicking action of paclitaxel
8. Conclusion
Chapter 4 The Overview of Studies on Huperzine A: A Natural Drug for the Treatment of Alzheimer?s Disease
Da-Yuan Zhu, Chang-Heng Tan, Yi-Ming Li
1. Introduction
1.1 Powerful AChEI originated from TCM
1.2 Alzheimer?s disease
2. Profiles of HA
2.1 Discovery of HA
2.2 Physical Appearance
3. Plant resources
4. Pharmacology
4.1 Effects on Cholinesterase Activity
4.2 Effects on Learning and Memory
4.3 Effects in Protection of Neuronal Cells
4.4 Toxicology
4.5 Effects on Miscellaneous Targets
5. Clinical trials
6. Synthesis of HA and its analogues
6.1 Synthesis of racemic HA
6.2 Synthesis of Optically Pure (-)-HA
6.3 Studies on the Structure-Activity Relationship
7. Structural biology
7.1 Interaction between HA and AChE
7.2 Structure-Based HA Analogs Design
8. ZT-1: New generation of HA ACHEI
8.1 Pharmacology
8.2 Toxicology
8.3 Pharmacokinetics
8.4 Clinical Trials

Chapter 5 Qinghaosu (artemisinin)---A Fantastic Antimalarial Drug from a Traditional Chinese Medicine
Ying Li, Hao Huang, and Yu-Lin Wu
1. Introduction
2. Qinghaosu and qinghao (Artemisia annua L. composites)
2.1. Discovery and structure determination of qinghaosu
2.2. The phytochemistry of qinghao and other natural products from qinghao
3. Reaction of qinghaosu
3.1. Reduction of qinghaosu
3.2. Acidic degradation of qinghaosu
3.3. Miscellaneous chemical reaction
3.4. Biotransformation
4. Chemical synthesis and biosynthesis
4.1. Partial synthesis and total synthesis
4.2. Biogenetic synthesis
5. Derivatives and antimalarial activity
5.1. Modification on C-12 of qinghaosu
5.2. Water-soluble qinghaosu derivatives
5.3. Modification on C-11 or/and C-12
5.4. Modification on C- 4 or/and C-12
5.5. Modification on C-3 or/and C-13
5.6. Modification on C-13
5.7. Modification on C-11 and C-12
5.8. Steroidal qinghaosu derivatives
5.9. Dimers
5.10. 1,2,4 -Trioxanes and 1,2,4,5 - tetraoxanes
6. Pharmacology and Chemical biology of qinghaosu and its derivatives
6.1 Bioactivities of qinghaosu derivatives and analogs
6.2 Early biologically morphologic observation of the antimalarial action of qinghaosu
6.3. The free radical reaction of qinghaosu and its derivatives with Fe(II)
6.4. Antimalarial activity and the free radical reaction of qinghaosu and its derivatives
6.5. Interaction of biomolecules with carbon-centered free radical
7. Conclusion
References
Chapter 6 Progress of Studies on the Natural Cembranoids from the Soft Coral Species of Sarcophyton Genus
Yulin Li, Lizeng Peng and Tao Zhang
1. Introduction
2. Cembrane-type constituents from Sarcophyton genus
2.1 Sarcophytols from Sarcophyton enus
2.2 The Other Cembrane-type Constituents from Sarcophyton Genus
3. Physiological action of sarcophytol A and Sarcophytol B
4. Total synthesis of the natural cembranoids
4.1 Total Synthesis of Sarcophytols
4.2 Total Synthesis of Cembrene A and C
4.3 Total Synthesis of Several Natural Epoxy Cembrenoids
4.4 Total Synthesis of Cembranolides
5. Studies on novel macrocyclization methods of cembrane-type diterpenoid
5.1 A Stille Cyclization Approach to (ñ)-Isocembrene
6. Acknowledgments
7. References
Chapter 7 Medicinal Chemistry of Ginkgolides from Ginkgo biloba
Kristan Stromgaard
1. Introduction
1.1 Ginkgo biloba extract
1.2 Isolation and structure elucidation of ginkgolides
1.3 Biosynthesis of ginkgolides
1.4 Chemistry of ginkgolides
2. Ginkgolides and the PAF Receptor
3. Ginkgolides and Glycine Receptors
4. Various Effects of Ginkgolides
5. Conclusions and Outlook

Chapter 8 Recent Progress in Calophyllum Coumarins as Potent Anti-HIV Agents
Lin Wang
1. Introduction
2. Anti-HIV-1 activity of Calophyllum coumarins
2.1 Anti-HIV-1 activity of Calanolides
2.2 Anti-HIV-1 activity of Inophyllums
2.3 Anti-HIV-1 activity of Cordatolides
3. Pharmacology of Calanolides
3.1 Pharmacology of (+)-Calanolide A (I)
3.2 Clinical trial of (+)-Calanolide A
4. Preparation of Calophyllum coumarins
4.1 Total synthesis of racemic Calophyllum coumarins
4.2 Preparation of optically active Calophyllum coumarins
5. Structure modification of Calanolides
6. Conclusion
Chapter 9 Recent Progress and Prospects on Plant-derived Anti-HIV Agents and Analogs
Dong-lei Yu, K.-H. Lee
1. Introduction
2. Khellactone Coumarin Analogs as Anti-HIV Agents
2.1 Suksdorfin as a new anti-HIV agent
2.2 Pyrano-3?,4? Stereoselectivity and Modification
2.3 Coumarin Skeleton Modification
2.4 Structure-Activity Relationship Conclusions
2.5 Mechanism of Action
3. Biphenyl Derivatives as Anti-HIV Agents
3.1 SAR analysis of naturally occurring dibenzocyclooctadiene lignans
3.2 Structural Modifications
3.3 SAR conclusions
3.4 Mechanism of Action of Biphenyl Derivatives
4. Triterpene betulinic acid derivatives as anti-HIV agents
4.1 Betulinic acid derivatives as entry inhibitors
4.2 Betulinic acid derivatives as maturation inhibitors
4.3 Bifunctional betulinic acid derivatives with two novel mechanisms of action
5. Conclusions
6. Acknowledgements
Chapter 10 Recent Progress on the Chemical Synthesis of Annonaceous Acetogenins and their structurally modified mimics
Tai-Shan Hu, Yu-Lin Wu and Zhu-Jun Yao
1. Introduction
2. Total synthesis of mono-THF acetogenins
3. Total synthesis of bis-THF acetogenins
4. Total synthesis of THP-containing acetogenins
5. Design and synthesis of mimics of acetogenins
6. Summary