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9780471660071

Medicinal Chemistry of Bioactive Natural Products

by ;
  • ISBN13:

    9780471660071

  • ISBN10:

    0471660078

  • Edition: 1st
  • Format: Hardcover
  • Copyright: 2006-03-10
  • Publisher: Wiley
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Summary

Current discoveries and research into bioactive natural products Medicinal Chemistry of Bioactive Natural Products provides a much-needed survey of bioactive natural products and their applications in medicinal chemistry. This comprehensive reference features articles by some of the world's leading scientists in the field on discovery, structure elucidation, and elegant synthetic strategies--developed for natural products--with an emphasis on the structure activity relationship of bioactive natural products. The topics have been carefully chosen on the basis of relevance to current research and to importance as clinicially useful agents. Rather than attempting to be a comprehensive encyclopedia of bioactive natural products, Medicinal Chemistry of Bioactive Natural Products guides the reader to the key developments in the field. By providing not only practical detail but a historical perspective on the chemistry and biology of the compounds under consideration, the book serves as a handy resource for researchers in their own work developing pharmaceuticals, and as an inspiring introduction for young scientists to the dynamic field of bioactive natural products research. Enhanced by examples with updated research results, the discussion covers such topics as: * The chemistry and biology of epothilones * Vancomycin and other glycopeptide antibiotic derivates * Antitumor and other related activities of Taxol and its analogs * The antimalarial properties of the traditional Chinese medicine, Quinghaosu (artemisinin) * Huperzine A: A natural drug for the treatment of Alzheimer's disease * The medicinal chemistry of ginkgolides from Ginkgo biloba * Recent progress in Calophyllum coumarins as potent anti-HIV agents * Plant-derived anti-HIV agents and analogs * Chemical synthesis of annonaceous acetogenins and their structurally modified mimics

Author Biography

XIAO-TIAN LIANG received his BS degree from the National Central University (China) in 1946 and his PhD degree from the University of Washington at Seattle (USA) in 1951. After postdoctoral work at Harvard University, he joined the faculty of the Institute of Materia Medica, Chinese Academy of Medical Sciences. In 1980, he was elected as an Academician of Academia Sinica (Chinese Academy of Sciences) and has served on the advisory editorial boards of Tetrahedron and Tetrahedron Letters, among other scientific journals. He coauthored more than 300 scientific papers and reviews, and has written or edited more than ten books.

WEI-SHUO FANG graduated from Beijing Medical University, and obtained his PhD degree from Peking Union Medical College (PUMC) in 1997. After postdoctoral training in the US, he joined the faculty of the Institute of Materia Medica, Chinese Academy of Medical Sciences & PUMC. He has conducted visiting study in the University of Illinois at Urbana-Champaign and coauthored more than thirty articles in peer-reviewed journals.

Table of Contents

Preface xiii
Contributors xvii
The Chemistry and Biology of Epothilones---Lead Structures for the Discovery of Improved Microtubule Inhibitors
1(34)
Karl-Heinz Altmann
Introduction
1(3)
Biological Effects of Epo B
4(5)
In Vitro Activity
4(4)
In Vivo Antitumor Activity
8(1)
Epothilone Analogs and SAR Studies
9(16)
Lactam-Based Analogs
9(1)
Modifications in the C9--C11 Region
10(3)
Modifications of the Epoxide Moiety
13(4)
C-26-Modified Analogs
17(1)
Side-Chain Modifications
18(4)
Aza-Epothilones
22(3)
Pharmacophore Modeling and Conformational Studies
25(1)
Epothilone Analogs in Clinical Development
26(2)
Conclusions
28(7)
Acknowledgments
29(1)
References
29(6)
The Chemistry and Biology of Vancomycin and Other Glycopeptide Antibiotic Derivatives
35(38)
Roderich D. Sussmuth
Introduction
35(2)
Classification of Glycopeptide Antibiotics
37(2)
Mode of Action
39(1)
Glycopeptide Resistance
40(3)
Biosynthesis
43(2)
Total Synthesis
45(2)
Glycopeptides as Chiral Selectors in Chromatography and Capillary Electrophoresis
47(2)
Structural Modifications of Glycopeptide Antibiotics and Structure Activity Relationship (SAR) Studies
49(24)
Modifications of Glycopeptide Antibiotics
51(7)
Rational Concepts for the Design of Novel Glycopeptides
58(6)
Conclusions
64(1)
Acknowledgment
65(1)
References
65(8)
Structure Modifications and Their Influences on Antitumor and Other Related Activities of Taxol and Its Analogs
73(70)
Wei-Shuo Fang
Qi-Cheng Fang
Xiao-Tian Liang
Discovery and Research and Development of Taxol
73(1)
Paclitaxel Analogs Active Against Normal Tumor Cells
74(32)
C-13 Side Chain
74(7)
A Ring and Its Substitutions
81(6)
B Ring and Its Substitutions
87(7)
C Ring and Its Substitutions
94(7)
D Ring
101(2)
Macrocyclic Analogs
103(1)
Miscellaneous
104(2)
Exploration on Mechanism of Paclitaxel Related to Tubulin Binding and Quest for Its Pharmacophore
106(5)
Biochemical Mechanism of Paclitaxel Related to Tubulin Binding
106(2)
Identification of Bioactive Conformations and Quest for a Pharmacophore for Paclitaxel
108(3)
Natural and Semisynthetic Taxoids Overcoming Multidrug Resistance (MDR)
111(6)
Structure-Modified Taxoids With Better Activity Toward MDR Tumors
111(3)
Nonpaclitaxel-Type Taxoids With MDR Reversal Activities
114(1)
Factors Contributing to the Resistance to Paclitaxel
115(2)
Design, Synthesis and Pharmacological Activity of Prodrugs of Paclitaxel
117(4)
Prodrugs Prepared to Improve Water Solubility
117(2)
Prodrugs Designed for Enhancing Specificity
119(2)
Other Biological Actions of Paclitaxel
121(1)
New Antimicrotubule Molecules Mimicking Action of Paclitaxel
122(1)
Conclusion
123(20)
Acknowledgments
124(1)
References
124(19)
The Overview of Studies on Huperzine A: A Natural Drug for the Treatment of Alzheimer's Disease
143(40)
Da-Yuan Zhu
Chang-Heng Tan
Yi-Ming Li
Introduction
143(2)
Powerful AChEI Originated From Traditional Chinese Medicine
143(1)
Alzheimer's Disease
144(1)
Profiles of HA
145(2)
Discovery of HA
145(1)
Physical Appearance of HA
145(2)
Plant Resources
147(1)
Pharmacology
148(4)
Effects on Cholinesterase Activity
148(1)
Effects on Learning and Memory
149(1)
Effects on the Protection of Neuronal Cells
150(2)
Toxicology
152(1)
Effects on Miscellaneous Targets
152(1)
Clinical Trials
152(2)
Synthesis of HA and Its Analogs
154(12)
Synthesis of Racemic HA
154(3)
Synthesis of Optically Pure (--)-HA
157(4)
Studies on the Structure--Activity Relationship
161(5)
Structural Biology
166(3)
Interaction Between HA and AChE
166(1)
Structure-Based HA Analog Design
167(2)
ZT-1: New Generation of HA AChE
169(14)
Pharmacology
170(1)
Toxicology
170(1)
Pharmacokinetics
171(1)
Clinical Trials
172(1)
Abbreviations
172(1)
References
173(10)
Qinghaosu (Artemisinin)---A Fantastic Antimalarial Drug from a Traditional Chinese Medicine
183(74)
Ying Li
Hao Huang
Yu-Lin Wu
Introduction
183(1)
Qinghaosu and Qinghao (Artemisia annua L. Composites)
184(13)
Discovery and Structure Determination of Qinghaosu
184(4)
The Phytochemistry of Qinghao and Other Natural Products from Qinghao
188(9)
Reaction of Qinghaosu
197(5)
Reduction of Qinghaosu
198(1)
Acidic Degradation of Qinghaosu
199(2)
Miscellaneous Chemical Reaction
201(1)
Biotransformation
201(1)
Chemical Synthesis and Biosynthesis of Qinghaosu
202(4)
Partial Synthesis and Total Synthesis of Qinghaosu
202(2)
Biogenetic Synthesis of Qinghaosu
204(2)
Derivatives and Antimalarial Activity
206(15)
Modification on C-12 of Qinghaosu
207(5)
Water-Soluble Qinghaosu Derivatives
212(3)
Modification on C-11 or/and C-12
215(1)
Modification on C-4 or/and C-12
215(1)
Modification on C-3 or/and C-13
216(1)
Modification on C-13
216(1)
Modification on C-11 and C-12
217(1)
Azaartemisinin
217(1)
Carbaartemisinin
218(1)
Steroidal Qinghaosu Derivatives
218(1)
Dimers and Trimers
219(2)
1,2,4-Trioxanes and 1,2,4,5-Tetraoxanes
221(1)
Pharmacology and Chemical Biology of Qinghaosu and Its Derivatives
221(18)
Bioactivities of Qinghaosu Derivatives and Analogs
221(3)
Early Biologically Morphologic Observation of the Antimalarial Action of Qinghaosu
224(1)
The Free Radical Reaction of Qinghaosu and Its Derivatives With Fe(II)
225(5)
Antimalarial Activity and the Free Radical Reaction of Qinghaosu and Its Derivatives
230(5)
Interaction of Biomolecules with Carbon-Centered Free Radical
235(3)
Another Point of View and Summary
238(1)
Conclusion
239(18)
References
239(18)
Progress of Studies on the Natural Cembranoids from the Soft Coral Species of Sarcophyton Genus
257(44)
Yulin Li
Lizeng Peng
Tao Zhang
Introduction
257(1)
Cembrane-Type Constituents from the Sarcophyton Genus
258(7)
Sarcophytols from the Sarcophyton Genus
258(2)
The Other Cembrane-Type Constituents from the Sarcophyton Genus
260(5)
Physiological Action of Sarcophytol A and Sarcophytol B
265(1)
Total Synthesis of the Natural Cembranoids
266(25)
Total Synthesis of Sarcophytols
267(4)
Total Synthesis of Cembrene A and C
271(6)
Total Synthesis of Several Natural Epoxy Cembrenoids
277(10)
Total Synthesis of Cembranolides
287(4)
Studies on Novel Macrocyclization Methods of Cembrane-Type Diterpenoids
291(10)
A Stille Cyclization Approach to (±)-Isocembrene
291(5)
Acknowledgments
296(1)
References
296(5)
Medicinal Chemistry of Ginkgolides from Ginkgo biloba
301(24)
Kristian Strømgaard
Introduction
301(7)
Ginkgo biloba Extract
301(3)
Isolation and Structure Elucidation of Ginkgolides
304(2)
Biosynthesis of Ginkgolides
306(1)
Chemistry of Ginkgolides
307(1)
Ginkgolides and the PAF Receptor
308(4)
Ginkgolides and Glycine Receptors
312(2)
Various Effects of Ginkgolides
314(1)
Conclusions and Outlook
315(10)
Acknowledgment
315(1)
References
315(10)
Recent Progress in Calophyllum Coumarins as Potent Anti-HIV Agents
325(32)
Lin Wang
Tao Ma
Gang Liu
Introduction
325(4)
Anti-HIV-1 Activity of Calophyllum Coumarins
329(4)
Anti-HIV-1 Activity of Calanolides
329(2)
Anti-HIV-1 Activity of Inophyllums
331(2)
Anti-HIV-1 Activity of Cordatolides
333(1)
Pharmacology of Calanolides
333(1)
Pharmacology of (+)-Calanolide A
333(1)
Clinical Trial of (+)-Calanolide A
334(1)
Preparation of Calophyllum Coumarins
334(15)
Total Synthesis of Racemic Calophyllum Coumarins
334(6)
Preparation of Optically Active Calophyllum Coumarins
340(9)
Structure Modification of Calanolides
349(1)
Conclusion
350(7)
References
351(6)
Recent Progress and Prospects on Plant-Derived Anti-HIV Agents and Analogs
357(42)
Donglei Yu
Kuo-Hsiung Lee
Introduction
357(1)
Khellactone Coumarin Analogs as Anti-HIV Agents
358(16)
Suksdorfin as a New Anti-HIV Agent
358(1)
Pyrano-3',4' Stereoselectivity and Modification
359(3)
Coumarin Skeleton Modification
362(11)
SAR Conclusions
373(1)
Mechanism of Action
374(1)
Biphenyl Derivatives as Anti-HIV Agents
374(5)
SAR Analysis of Naturally Occurring Dibenzocyclooctadiene Lignans
374(2)
Structural Modifications
376(2)
SAR Conclusions
378(1)
Mechanism of Action of Biphenyl Derivatives
378(1)
Triterpene Betulinic Acid Derivatives as Anti-HIV Agents
379(12)
Betulinic Acid Derivatives as Entry Inhibitors
379(7)
Betulinic Acid Derivatives as Maturation Inhibitors
386(3)
Bifunctional Betulinic Acid Derivatives with Dual Mechanisms of Action
389(2)
Conclusions
391(8)
Acknowledgments
391(1)
References
391(8)
Recent Progress on the Chemical Synthesis of Annonaceous Acetogenins and Their Structurally Modified Mimics
399(44)
Tai-Shan Hu
Yu-Lin Wu
Zhu-Jun Yao
Introduction
399(2)
Total Synthesis of Mono-THF Acetogenins
401(12)
Total Synthesis of Bis-THF Acetogenins
413(9)
Total Synthesis of THP-Containing Acetogenins
422(6)
Design and Synthesis of Mimics of Acetogenins
428(9)
Summary
437(6)
References
437(6)
Index 443

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