Efficiency in Natural Product Total Synthesis

ISBN-13: 9781118605400 / Angielski / Twarda / 2018 / 512 str.

Pei–Qiang Huang; Zhu–Jun Yao; Richard Hsung

Opis

Uniting the key organic topics of total synthesis and efficient synthetic methodologies, this book clearly overviews synthetic strategies and tactics applied in total synthesis, demonstrating how the total synthesis of natural products enables scientific and drug discovery. - Focuses on efficiency, a fundamental and important issue in natural products synthesis that makes natural product synthesis a powerful tool in biological and pharmaceutical science
- Describes new methods like organocatalysis, multicomponent and cascade reactions, and biomimetic synthesis
- Appeals to graduate students with two sections at the end of each chapter illustrating key reactions, strategies, tactics, and concepts; and good but unfinished total synthesis (synthesis of core structure) before the last section
- Compiles examples of solid phase synthesis and continuing flow chemistry-based total synthesis which are very relevant and attractive to industry R&D professionals

Spis treści

Preface
Pei–Qiang Huang, Richard P. Hsung and Zhu–Jun Yao

Introduction
by Pei–Qiang Huang

Chapter 1. Principles for Synthetic Efficiency and Expansion of the Field
by Pei–Qiang Huang

1.1 Concepts of efficiency in the total synthesis of natural products

1.1.1 Ideal synthesis

1.1.2 Selectivity

1.1.3 Green synthesis

1.1.4 Atom–economy

1.1.5 E–factors

1.1.6 Step–economy

1.1.7 Pot–economy and PASE (pot, atom and step economy)

1.1.8 Redox–Economy

1.1.9 Protecting group–free synthesis

1.1.10 Multicomponent reactions one–pot reactions

1.1.11 Scalability

1.1.12 Convergent synthesis

1.2 Biomimetic synthesis

1.2.1 Basic logics of biosynthesis

1.2.2 Tandem, cascade, and domino reactions one–pot reactions

1.2.3 Site and stereoselective reactions

1.2.4 The C–H bond functionalization strategy

1.2.5 The building–block strategy

1.2.6 The collective synthesis strategy

1.2.7 The oligamerization tactic

1.3 Expansion of the field: Chemical biology/ Chemical genetics

1.3.1 Diversity–oriented synthesis (DOS)

1.3.2 Function–oriented synthesis (FOS)

1.3.3 Biology–oriented synthesis (BIOS)

1.3.4 Lead–Oriented Synthesis (LOS)

1.4 Addressing the threats that human may face with in the near future

1.4.1 The A. G. Myers endeavor

1.4.2 The D. L. Boger s endeavor

Chapter 2. Selected Procedure–Economical Enantioselective Total Syntheses of Natural Products
by Pei–Qiang Huang

2.1 One–step/one–pot total synthesis of natural products/ drugs

2.1.1 Robinson s one–step synthesis of tropinone

2.1.2 Hayashi s One–Pot Synthesis of ABT–341

2.2. Two–step/two–pot total synthesis of natural products

2.2.1 Hayashi s two–pot Synthesis of (–)–oseltamivir

2.2.2 Ma s two–pot Synthesis of (–)–oseltamivir

2.2.3 Li s two–step chemoenzymatic enantioselective total synthesis of aszonalenin

2.2.4 Ishikawa s two–step enantioselective total syntheses of (+)–WIN 64821 and (+)–naseseazine B

2.3. Three–step/three–pot total syntheses of natural products

2.3.1 Carreira s three–step asymmetric total syntheses of (+)–Aszonalenin and (–)–Brevicompanine B

2.3.2 Husson s three–step asymmetric total synthesis of (–)–Sibirine

2.3.3 MacMillan s three–step asymmetric total synthesis of (+)–frondosin B

2.3.4 Hayashi s three–pot enantioselective total synthesis of PGE1 methyl ester

2.3.5 Porco, Jr s three–pot enantioselective total synthesis of (–)–Hyperibone K

2.4. Four–step total synthesis of natural products

2.4.1. Lawrence s four–step enantioselective total synthesis of angiopterlactone A

2.4.2. Maimone s Four–step synthesis of (+)–cardamom peroxide

2.4.3. Xie, Lai, and Ma s Four–step enantioselective total synthesis of (–)–chimonanthine

2.4.4. Huang s Four–step enantioselective total synthesis of (–)–chaetominine

2.5. Five–step/pot total synthesis of natural products

2.5.1. Carreira s Five–step Stereodivergent Dual Catalysis–Based Enantioselective Total Syntheses of All Stereoisomers of D9–Tetrahydrocannabinols

2.5.2. Studer s Five–step Total Synthesis of (+)–Machaeriol B and (+)–Machaeriol D

2.5.3. Cook s Five–pot enantioselective total synthesis of (+)–Artemisinin

2.5.4. Corey s Five–step enantioselective total synthesis of Aflatoxin B2

2.6. Six–step enantioselective total synthesis of natural products

2.6.1. Comins six–step enantioselective total synthesis of (S)–Camptothecin

2.6.2. Krische s six–step total synthesis of Cyanolide A

2.7. Seven–step enantioselective total synthesis of natural products

2.7.1. Baran s 7–10–step enantioselective total syntheses of hapalindole–type natural products

2.7.2. Aggarwa s seven–step enantioselective total syntheses of PGF2a

2.7.3. Echavarren s seven–step enantioselective total syntheses of aromadendrane sesquiterpenes

2.7.4. Zhu s seven–step enantioselective total synthesis of Peganumine A

2.7.5. Rychnovsky s seven–step synthesis of Lycopodium alkaloid (+)–Fastigiatine

2.8. Eight–step enantioselective total synthesis of natural products

2.8.1. Overman s eight–step synthesis of trans–clerodane diterpenoids

2.8.2. Chain s eight–step enantioselective synthesis of (–)–Englerin A

2.8.3. Shenvi s eight–step enantioselective total synthesis of (–)–Jiadifenolide

2.8.4. Maimone′s eight–step enantioselective total synthesis of (+)–Chatancin

2.8.5. Wipf s eight–step enantioselective total synthesis of cycloclavine

2.9. Nine–step Enantioselective Total Syntheses of Natural Products

2.9.1. Stoltz s Nine–Step Enantioselective Total Synthesis of Cyanthiwigin F

2.9.2. Maimone s nine–step enantioselective total synthesis of ( )–6–epi–ophiobolin N

2.9.3. MacMillan s Nine–Step Enantioselective Total Synthesis of ( )–Vincorine

2.9.4. Ramharter s Nine–Step Enantioselective Total Synthesis of (+)–Lycoflexine

2.9.5. Gao s and Theodorakis Nine–Step Enantioselective Total Syntheses of (+)–Fusarisetin A

2.10. Ten/eleven–step Enantioselective Total Syntheses of Natural Products

2.10.1. Lin s Ten–Step Enantioselective Total Synthesis of Huperzine A

2.10.2. Trauner s Ten–Step Enantioselective Total Synthesis of (+)–loline

2.10.3. Zhai s Ten–Step Enantioselective Total Synthesis of (+)–Absinthin

2.10.4. Baran s 11–Step Enantioselective Total Synthesis of ( )–Maoecrystal V

2.11. Fourteen/fifteen–step Enantioselective Total Synthesis of Natural Products

2.11.1. Baran s 14–Step Enantioselective Total Synthesis of (–)–Ingenol

2.11.2. Reisman s 15–Step Enantioselective Total Synthesis of (+)–Ryanodol

2.11.3. Johnson s 15–Step Enantioselective Total Synthesis of (+)–Pactamycin

Chapter 3. Diels–Alder Cascades in Natural Product Synthesis
by Richard P. Hsung, John B. Feltenberger, Zhi–Xiong Ma, Li–Chao Fang

3.1 Introduction

3.2 Cascades Initiated by Coupling of Preformed Diene/Dienophile

3.3 Diene/Dienophiles Formation Followed by Diels–Alder

3.4 Rearrangement–Initiated Diels–Alder Cascades

3.5 Cyclization–Initiated Diels–Alder Cascades

3.6 Diels–Alder Initiated Cascades

3.7 Concluding Remarks

3.8 References

Chapter 4. Organometallics–based Catalytic (Asymmetric) Synthesis of Natural Products
by Yun Li CBin Cheng, Zhi–Qiang Ma, Peng Gao, Xin Chen, Wei–He Zhang, Han–Wei Hu, Fang Fang, Hong–Bin Zhai

4.1 Introduction

4.2 Au Catalyzed Reaction in Total Synthesis

4.3 Ag catalyzed reactions in total synthesis

4.4 Pt Catalyzed Reactions in Total Synthesis

4.4.1 Pt Catalyzed Enyne cycloisomerization reactions

4.5 Co–Catalyzed Pauson–Khand Reactions and hetero–Pauson–Khand Reactions in Total Synthesis

4.6 Cu–Catalyzed Reactions in Total Synthesis

4.6.1 Asymmetric Conjugate Addition

4.6.2 Arene Cyclopropanation

4.7 Chromium–Catalyzed Reactions in Total Synthesis

4.8 Fe–Mediated Coupling Reaction in Total Synthesis

4.8.1 Reaction with Acid Chlorides

4.8.2 Reaction with Alkenyl Electophiles

4.8.3 Reaction with Aryl Halides

4.8.4 Reaction with Alkyl Halides

4.8.5 Related Iron–Catalyzed C–C Bond Formations

4.8.6 Iron–Catalyzed C–O, C–S, and C–N Cross Coupling

4.9 Mn–Mediated Coupling Reactions in Total Synthesis

4.10 Ni–Catalyzed Reactions in Total Synthesis

4.10.1 Ni–Catalyzed Cycloadditions.

4.10.2 Ni–Catalyzed Coupling Reactions.

4.11 Pd–Catalyzed Cross Coupling Reactions in Total Synthesis

4.11.1 Heck reaction in total synthesis

4.11.2 Suzuki Reaction in total synthesis

4.11.3 Stille Reaction in total synthesis

4.11.4 Tsuji–Trost reaction in total synthesis

4.11.5 Negishi reaction in total synthesis

4.11.6 Pd catalyzed domino reaction in total synthesis

4.12 Rh–Catalyzed (C H Functionalization by Metal Carbenoid and Nitrenoid Insertion) Reactions in Total Synthesis

4.13 Ru–Catalyzed RCM and RCAM in Total Synthesis

4.14 References

Chapter 5. C–H Activation–Based Strategy for Natural Product Synthesis
by Yun Li, Fang Fang, Hong–Bin Zhai

5.1 Introduction

5.2 Recently completed total syntheses of natural product via C–H activation approach

5.3 References

Chapter 6. Recent Applications of Kagan s Reagent (SmI2) in Natural Product Synthesis
by Stellios Arseniyadis, Erica Benedetti, Cyril Bressy, Michael Smietana

6.1 Background

6.2 SmI2–mediated reactions in natural product total synthesis

6.2.1 Synthesis of acutiphycin

6.2.2 Synthesis of brevetoxin B

6.2.3. Synthesis of (±) vigulariol

6.2.4. Synthesis of diazonamide A

6.2.5. Synthesis of epothilone A

6.2.6. Synthesis of strychnine

6.2.7. Synthesis of the ABC ring of paclitaxel

6.2.8. Miscellaneous

6.3. CONCLUSION

6.4 References

Chapter 7. Asymmetric Organocatalysis in Total Synthesis of Complex Natural Products
by Zheng–Qing Ye, Gang Zhao

7.1 Backgroud

7.2 Total Synthesis of Alkaloids

7.2.1 Synthesis of (–)–Flustramine B

7.2.2 Enantioselective Total Synthesis of (+)–Minfiensine

7.2.3 Concise Synthesis of (–)–Nakadomarin A

7.2.4 Collective Total Synthesis of Strychnine, Akuammicine, Aspidospermidine, Vincadifformine, Kopsinine and Kopsanone

7.2.5 Asymmetric Synthesis of (–)–Lycoramine, (–)–Galanthamine and (+)–Lunarine

7.2.6 Total Synthesis of the Galbulimima Alkaloid (–)–GB17

7.3 Total Synthesis of Terpenoids and Related Multicyclic Natural Products

7.3.1 Total Synthesis of (+)–Hirsutene

7.3.2 Total Synthesis of (–)–Brasoside and (–)–Littoralisone

7.3.3 Concise Synthesis of Ricciocarpin A

7.3.4 Total Synthesis and Absolute Stereochemistry of Seragakinone A

7.4 Total Synthesis of Macrolides (or macrolactams)

7.4.1 Total Synthesis and Structural Revision of Callipeltoside C

7.4.2 Total Synthesis of (+)–Cytotrienin A

7.4.3 Total Synthesis of Diazonamide A

7.5 Total Synthesis of Peptide Natural Product

7.5.1 Total Synthesis of Chloptosin

7.6 Summary of the Key Reactions and Tactics

7.7 References

Chapter 8. Multicomponent reactions in Natural Product Synthesis
by Stellios Arseniyadis, Erica Benedetti, Cyril Bressy, Michael Smietana

8.1 Background

8.2 Multicomponent reactions in natural product synthesis

8.2.1 Synthesis of martinelline by Powell and Batey

8.2.2 Synthesis of eurystatin by Schmidt and Weinbrenner

8.2.3 Synthesis of motuporin by Bauer and Armstrong

8.2.4 Synthesis of thiomarinol by Gao and Hall

8.2.5 Synthesis of minquartynoic acid by Gung and coworkers

8.2.6 Synthesis of spongistatin 2 by Smith and co–workers

8.2.7 Synthesis of vannusal A and B by Nicolaou and coworkers

8.2.8 Synthesis of Calystegine B–4 by Pyne and coworkers

8.2.9 Synthesis of jerangolid D by Marko and Pospisil

8.2.10 Synthesis of ( )–nakadomarin A by Young and Kerr

8.3 Conclusion

8.4 References

Chapter 9. Renewable Resource–Based Building Blocks/ Chirons for the Total Synthesis of Natural Products
by Tony Kung Ming Shing

9.1 Introduction

9.1.1 The Chiron Approach towards the Total Synthesis of Natural Products

9.1.2 General Survey of Natural Chirons

9.2 Total Synthesis of Alkaloids

9.2.1 Amino Acids as Starting Chiron

9.2.2 Carbohydrates as Starting Chiron

9.2.3 Terpene and –hydroxyl acid as Starting Chirons

9.3 Total Synthesis of Terpenoids

9.3.1 Terpene as Starting Chiron

9.4 Total Synthesis of Miscellaneous Natural Products

9.4.1 Amino Acids as Starting Chirons

9.5 Conclusions and Perspectives

9.6 References

Chapter 10. Natural Product Synthesis for Drug Discovery and Chemical Biology
by Zhu–Jun Yao and Shouyun Yu

10.1 The Importance of Bioactive Natural Products in Biological Investigation

10.2 Bioactive Natural Product–inspired Chemical Biology

10.3 Natural Products in Drug Discovery

10.3.3 Natural Products as Antibody Drug Conjugate (ADC) Payloads

10.4 TOS, DOS, FOS and BOS in Natural Product Synthesis

10.4.1 Target–Oriented Synthesis (TOS)

10.4.2 Diversity–Oriented Synthesis (DOS)

10.4.3 Function–Oriented Synthesis (FOS)

10.4.4 Biology–Oriented Synthesis (BIOS)

10.5 Semi–synthesis

10.6 Representative Natural Product Drugs and Their Synthesis

10.6.1. Nicolaou and Yang s Synthesis of Taxol

10.6.2. Danishefsky s Synthesis of Epothilone A

10.6.3. Smith s Synthesis of Kendomycin

10.6.4. Yao s Synthesis of Camptothecin

10.6.5. Nicolaou and Li s Synthesis of Platensimycin

10.6.6. Shasun Pharma Solutions Ltd. s Synthesis of Huperzine A

10.6.7. Baran s Synthesis of Ingenol

10.7 Overview and Perspective

10.8 References

Chapter 11. Modern technologies in natural product synthesis
by Zhu–Jun Yao and Shouyun Yu

11.1 Visible–light Photochemistry

11.2 Electrochemistry

11.3 Flow Chemistry

11.4 Flow Photochemistry

11.5 Flow Electrochemistry

11.6 Overview and Perspective

11.7 References

Chapter 12. Concluding Remarks and Perspective
by Pei–Qiang Huang, Richard P. Hsung, Zhi–Xiong Ma, and Zhu–Jun Yao

12.1 The enantioselective total synthesis of natural products

12.2 A novel model of total synthesis: the combination of chemical synthesis with synthetic biology

12.3 Robot–chemist and the generalized automation of small–molecule synthesis

12.4 A Synergistic Future with Academia and Industry Coming to the Same Table

INDEX

O autorze

Pei–Qiang Huang, PhD, is Professor of Chemistry and Dean of the College of Chemistry and Chemical Engineering at Xiamen University.

Zhu–Jun Yao, PhD, is Cyrus Tang Chair Professor and University Distinguished Professor at Nanjing University.

Richard Hsung, PhD, is a professor of Pharmaceutical Sciences and Chemistry at the Pharmacy Experience University of Wisconsin.

Blurb

Total synthesis of natural products is one of organic chemistry s oldest disciplines, enabling chemists to duplicate nature and providing the means to examine natural phenomena more closely. The development of drugs, the examination of biopathways and many other achievements would not have been possible without total synthesis for example, about half of the drugs currently in clinical use have their origins in natural products. New concepts, strategies, and tactics for efferent total synthesis of natural products will continue as a major pursuit for synthetic organic, medicinal, and process chemists for a long time to come.

Uniting the key organic topics of total synthesis and efficient synthetic methodologies, Efficiency in Natural Products Total Synthesis clearly overviews the strategies and tactics applied in total synthesis, demonstrating how the total synthesis of natural products enables scientific and drug discovery. The state–of–the–art topics covered include: economic and protecting–group–free synthesis, computer–aided total synthesis, catalytic asymmetric synthesis, biomimetic and bio–inspired synthesis, as well as different classes of organic reactions. Other chapters address chemical building blocks, technologies of chemical and biological space, and synthetic biology. A key part of the coverage is the illustration of how these practices and strategies influence drug discovery and chemical biology.

Chemical researchers working with natural products synthesis will find this book to be an important reference and resource that offers a number of valuable features:

          Focus on efficiency, a fundamental and important issue in natural products synthesis that makes natural product synthesis a powerful tool in biological and pharmaceutical science
          Discussion of new methods like organocatalysis, multicomponent and cascade reactions, and biomimetic synthesis
          Sections at the end of each chapter illustrating key reactions, strategies, tactics, and concepts; and good but unfinished total synthesis (synthesis of core structure) before the last section
          Examples of solid phase synthesis and continuing flow chemistry–based total synthesis, which are very relevant for industrial R&D