Medicinal Chemistry of Bioactive Natural Products

by Liang, Xiao-Tian; Fang, Wei-Shuo

• ISBN13: 9780471660071
• ISBN10: 0471660078
• Edition: 1st
• Format: Hardcover
• Copyright: 2006-03-10
• Publisher: Wiley
• More Book Details
• Purchase Benefits

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