Classics in Total Synthesis 3

Produktbeschreibung

Retaining his excellent, proven approach, world-famous chemist and passionate teacher K.C. Nicolaou and his student Jason S. Chen compile here the important strategies and tools employed to construct complex molecules. Through 42 syntheses of 25 challenging natural products they explain the key steps of the synthetic pathway, highlighting the major developments for easier understanding, and contrasting these to other synthetic methods. Similar to its predecessors and completing a trilogy, this textbooks analyzes the syntheses in a didactic manner, with several chapters including mini-reviews of key methodologies, and an emphasis on the history, mechanism, scope, and generality of the reactions. In contrast to the first two volumes, this new one features full-color frontispieces. A wonderful tool for learning and teaching, and a must-have for all current and future organic, medicinal and biological chemists.

From reviews of "Classics in Total Synthesis", Volumes I and II:

"...a volume, (...) which any chemist with an interest in synthetic organic chemistry will wish to acquire." JACS

"...this superb book (...) will be an essential purchase for many organic chemists." Nature

"... Classics II is undoubtedly an excellent bargain that is highly recommended to everybody interested in advanced organic chemistry..." Angewandte Chemie 

Inhaltsverzeichnis

Chapter 1 Introduction: The Advancing Field of Total Synthesis

1.1 Targets 2

1.2 Strategies and Methods 2

1.3 Classics in Total Synthesis III 10

Chapter 2 Tetrodotoxin
Y. Kishi; J. Du Bois (1972; 2003)

2.1 Introduction 13

2.1.1 Aliphatic C-H Bond Functionalization 16

2.2 Kishi's Retrosynthetic Analysis and Strategy 35

2.3 Kishi's Total Synthesis 37

2.4 Du Bois' Retrosynthetic Analysis and Strategy 43

2.5 Du Bois' Total Synthesis 45

2.6 Conclusion 52

Chapter 3 Discodermolide
Novartis: S. J. Mickel; I. Paterson; A. B. Smith, III (2004)

3.1 Introduction 57

3.2 Retrosynthetic Analysis and Strategy 61

3.3 Total synthesis 65

3.3.1 Synthesis of the Common Precursor 65

3.3.2 Divergent Synthesis of the Fragments 67

3.3.3 Fragment Coupling and Completion of the Synthesis 72

3.4 Conclusion 79

Chapter 4 Azaspiracid-1
K. C. Nicolaou; D. A. Evans (2004, 2006; 2007)

4.1 Introduction 83

4.2 Nicolaou's Retrosynthetic Analysis and Strategy 92

4.3 Nicolaou's Total Synthesis 95

4.3.1 Synthesis of the ABCDE Ring System 95

4.3.2 Synthesis of the FHI Ring System 101

4.3.3 Fragment Coupling and Completion of the Synthesis 105

4.4 Evans' Retrosynthetic Analysis and Strategy 107

4.5 Evans' Total Synthesis 108

4.5.1 Synthesis of the ABCD Ring System 108

4.5.2 Synthesis of the EFGHI Ring System 115

4.5.3 Fragment Coupling and Completion of the Synthesis 121

4.6 Conclusion 121

Chapter 5 Thiostrepton
K. C. Nicolaou (2004)

5.1 Introduction 127

5.2 Retrosynthetic Analysis and Strategy 135

5.3 Total Synthesis 138

5.3.1 Synthesis of the Dehydropiperidine Fragment 138

5.3.2 Synthesis of the Other Fragments 144

5.3.3 Fragment Coupling and Completion of the Synthesis 152

5.4 Conclusion 156

Chapter 6 Pentacycloanammoxic Acid Methyl Ester
E. J. Corey (2004, 2006)

6.1 Introduction 161

6.1.1 Synthesis of Ladderane Compounds 164

6.2 First-Generation Retrosynthetic Analysis and Strategy 171

6.3 First-Generation Total Synthesis 172

6.4 Second-Generation Retrosynthetic Analysis and Strategy 177

6.5 Second-Generation Total Synthesis 179

6.6 Conclusion 182

Chapter 7 Littoralisone, Oseltamivir (Tamiflur), and Hirsutellone B
D. W. C. MacMillan; Y. Hayashi; K. C. Nicolaou (2005; 2009; 2009)

7.1 Introduction 187

7.1.1 Catalysis by Cinchona Alkaloids 190

7.1.2 Enamine Catalysis 199

7.1.3 Iminium Catalysis and Enamine-Iminium Cascades 209

7.1.4 Other Examples of Organocatalysis 217

7.2 Introduction to Littoralisone 225

7.2.1 Retrosynthetic Analysis of Littoralisone 227

7.3 Total Synthesis of Littoralisone 228

7.4 Introduction to Oseltamivir (Tamiflur) 232

7.4.1 Retrosynthetic Analysis of Oseltamivir (Tamiflur) 235

7.5 Total Synthesis of Oseltamivir (Tamiflur) 236

7.6 Introduction to Hirsutellone B 237

7.6.1 Retrosynthetic Analysis of Hirsutellone B 240

7.7 Total Synthesis of Hirsutellone B 242

7.8 Conclusion 248

Chapter 8 Rubicordifolin and Rubioncolin B
D. Trauner (2005, 2008)

8.1 Introduction 255

8.2 Retrosynthetic Analysis of Rubicordifolin 258

8.3 Total Synthesis of Rubicordifolin 259

8.4 Retrosynthetic Analysis of Rubioncolin B 262

8.5 Total Synthesis of Rubioncolin B 262

8.6 Conclusion 266

Chapter 9 Cyanthiwigins U and F
A. J. Phillips; B. M. Stoltz (2005; 2008)

9.1 Introduction 271

9.2 Phillips' Retrosynthetic Analysis and Strategy 276

9.3 Phillips' Total Synthesis 277

9.4 Stoltz' Retrosynthetic Analysis and Strategy 281

9.5 Stoltz' Total Synthesis 282

9.6 Conclusion 286

Chapter 10 Stephacidin B
A. G. Myers; P. S. Baran; R. M. Williams (2005; 2005; 2007)

10.1 Introduction 291

10.2 Myers' Retrosynthetic Analysis and Strategy 296

10.3 Myers' Total Synthesis 298

10.4 Baran's Retrosynthetic Analysis and Strategy 303

10.5 Baran's Total Synthesis 305

10.6 Williams' Retrosynthetic Analysis and Strategy 311

10.7 Williams' Total Synthesis 312

10.8 Conclusion 317

Chapter 11 Abyssomicin C and atrop-Abyssomicin C
E. J. Sorensen; K. C. Nicolaou (2005; 2006)

11.1 Introduction 321

11.2 Sorensen's Retrosynthetic Analysis and Strategy 324

11.3 Sorensen's Total Synthesis of Abyssomicin c 327

11.4 Nicolaou's Retrosynthetic Analysis and Strategy 331

11.5 Nicolaou's Total Synthesis of Abyssomicin c and atrop-Abyssomicin c 331

11.5.1 Chemistry and Biology of the Abyssomicins 338

11.6 Conclusion 342

Chapter 12 Tetracycline
A. G. Myers (2005, 2007)

12.1 Introduction 345

12.1.1 Singlet Oxygen Ene Reactions 356

12.2 Retrosynthetic Analysis and Strategy 361

12.3 Total Synthesis 364

12.4 Conclusion 373

Chapter 13 Bisanthraquinone Natural Products
K. C. Nicolaou (2005, 2009)

13.1 Introduction 377

13.2 Retrosynthetic Analysis and Strategy Toward

2,2l-epi-Cytoskyrin A, Rugulosin, and Rugulin 381

13.3 Total Synthesis of 2,2l-epi-Cytoskyrin A, Rugulosin, and Rugulin 384

13.4 Retrosynthetic Analysis and Strategy Toward Antibiotic BE-43472B 394

13.5 Total Synthesis of Antibiotic BE-43472B 395

13.6 Conclusion 402

Chapter 14 Garsubellin A
M. Shibasaki, M. Kanai; S. J. Danishefsky (2005; 2006)

14.1 Introduction 407

14.2 Shibasaki and Kanai's Retrosynthetic Analysis and Strategy 413

14.3 Shibasaki and Kanai's Total Synthesis 413

14.4 Danishefsky's Retrosynthetic Analysis and Strategy 421

14.5 Danishefsky's Total Synthesis 423

14.6 Conclusion 429

Chapter 15 Welwitindolinone A
P. S. Baran; J. L. Wood (2005; 2006)

15.1 Introduction 433

15.2 Baran's Retrosynthetic Analysis and Strategy 435

15.3 Baran's Total Synthesis 435

15.4 Wood's Retrosynthetic Analysis and Strategy 440

15.5 Wood's Total Synthesis 440

15.6 Conclusion 446

Chapter 16 Iejimalide B
A. Fürstner (2006, 2007)

16.1 Introduction 449

16.2 Retrosynthetic Analysis and Strategy 451

16.3 Total Synthesis 454

16.3.1 Synthesis of the Fragments 454

16.3.2 Fragment Coupling and Completion of the Synthesis 462

16.3.3 Alternative Synthetic Approach 464

16.4 Conclusion 466

Chapter 17 Kedarcidin Chromophore and Maduropeptin Chromophore
A. G. Myers; M. Hirama, M. Inoue, I. Sato (2007; 2009)

17.1 Introduction 469

17.2 Retrosynthetic Analysis and Strategy for Kedarcidin Chromophore 483

17.3 Total Synthesis of Kedarcidin Chromophore 487

17.3.1 Synthesis of the Fragments 487

17.3.2 Fragment Coupling and Completion of the Synthesis 496

17.4 Retrosynthetic Analysis and Strategy for Maduropeptin Chromophore 502

17.5 Total Synthesis of Maduropeptin Chromophore 505

17.5.1 Synthesis of the Fragments 505

17.5.2 Fragment Coupling and Completion of the Synthesis 511

17.6 Conclusion 518

Chapter 18 Biyouyanagin A
K. C. Nicolaou (2007)

18.1 Introduction 523

18.1.1 Photoinduced [2þ2] Cycloadditions 526

18.2 Retrosynthetic Analysis and Strategy 535

18.3 Total Synthesis 537

18.4 Conclusion 541

Chapter 19 Azadirachtin
S. V. Ley (2007, 2009)

19.1 Introduction 545

19.1.1 Selected Strategies for the Construction of the Congested C8-C14 Bond 547

19.2 Retrosynthetic Analysis and Strategy 553

19.3 Synthesis 555

19.4 Conclusion 562

Chapter 20 Resveratrol-Derived Natural Products
S. A. Snyder; K. C. Nicolaou, D. Y.-K. Chen (2007, 2009; 2009, 2010)

20.1 Introduction 567

20.2 Snyder's Retrosynthetic Analysis and Strategy for a Collection of
Resveratrol-Derived Natural Products 571

20.3 Snyder's Total Synthesis of a Collection of Resveratrol-Derived Natural
Products 574

20.4 Nicolaou and Chen's Retrosynthetic Analysis and Strategy for Hopeahainol A
and Hopeanol 583

20.5 Nicolaou and Chen's Total Synthesis of Hopeahainol A and Hopeanol 585

20.6 Conclusion 592

Chapter 21 Chlorosulfolipid Cytotoxin
E. M. Carreira (2009)

21.1 Introduction 595

21.1.1 Asymmetric Halogenation Reactions 600

21.2 Retrosynthetic Analysis and Strategy 608

21.3 Total Synthesis 609

21.4 Conclusion 612

Chapter 22 Sporolide B
K. C. Nicolaou (2009)

22.1 Introduction 617

22.1.1 o-Quinone Diels-Alder Cycloadditions 620

22.1.2 Transition Metal-Catalyzed [2þ2þ2] Cycloadditions 624

22.2 Retrosynthetic Analysis and Strategy 627

22.3 Total Synthesis 629

22.4 Conclusion 635

Chapter 23 11,11'-Dideoxyverticillin A and Chaetocin
M. Movassaghi; M. Sodeoka (2009; 2010)

23.1 Introduction 639

23.2 Retrosynthetic Analysis and Strategy for 11,11l-Dideoxyverticillin A 646

23.3 Total Synthesis of 11,11l-Dideoxyverticillin A 648

23.4 Retrosynthetic Analysis and Strategy for Chaetocin 651

23.5 Total Synthesis of Chaetocin 653

23.6 Conclusion 655

Chapter 24 Vannusal B
K. C. Nicolaou (2009)

24.1 Introduction 659

24.1.1 SmI 2 -Mediated Ketyl-Olefin Cyclization 662

24.2 Retrosynthetic Analysis and Strategy 670

24.3 Total Synthesis 672

24.3.1 Synthesis of the Left Domain 672

24.3.2 Synthesis of the Right Domain 675

24.3.3 Fragment Coupling, Completion of the Synthesis, and Structural
Reassignment 678

Chapter 25 Haplophytine
T. Fukuyama, H. Tokuyama; K. C. Nicolaou, D.Y.-K. Chen (2009; 2009)

25.1 Introduction 689

25.2 Fukuyama and Tokuyama's Retrosynthetic Analysis and Strategy 691

25.3 Fukuyama and Tokuyama's Total Synthesis 695

25.3.1 Synthesis of the Left Domain 695

25.3.2 Synthesis of the Right Domain 700

25.3.3 Fragment Coupling and Completion of the Synthesis 702

25.4 Nicolaou and Chen's Retrosynthetic Analysis and Strategy 706

25.5 Nicolaou and Chen's Total Synthesis 706

25.5.1 Synthesis of the Left Domain 706

25.5.2 Synthesis of the Right Domain 708

25.5.3 Fragment Coupling and Completion of the Synthesis 711

25.6 Conclusion 716

Chapter 26 Palau'amine
P. S. Baran (2010)

26.1 Introduction 719

26.2 Retrosynthetic Analysis and Strategy 722

26.3 Total Synthesis 725

26.4 Conclusion 730

Image / Photo Credits 733

Author Index 735

Subject Index 738 

Autoreninfo

K.C. Nicolaou holds joint appointments at The Scripps Research Institute, where he is the Chairman of the Department of Chemistry and holds the Darlene Shiley Chair in Chemistry and the Aline W. and L.S. Skaggs Professorship of Chemical Biology, and the University of California, San Diego, where he is Distinguished Professor of Chemistry. His impact on chemistry, biology and medicine flows from his research works in chemical synthesis and chemical biology described in numerous publications and patens. For his contributions to science and education, he was elected Fellow of the New York Academy of Sciences, Fellow of the American Academy of Arts and Sciences, Member of the National Academy of Sciences, USA, Member of the German Academy of Sciences Leopoldina, and Corresponding Member of the Academy of Athens, Greece. He is the recipient of many prizes, awards and honors.

Jason S. Chen received his A.B. and A.M. degrees in Chemistry from Harvard University in 2001. After two years as a medicinal chemist at Enanta Pharmaceuticals, he began graduate studies at The Scripps Research Institute under the guidance of Professor K.C. Nicolaou. He received a National Defense Science and Engineering Graduate fellowship, and completed his Ph.D. studies in 2008. He currently is a post-doctoral fellow in Professor Nicolaou's laboratory.