Biomimetic organic synthesis

Biomimetic Organic Synthesis
Edited by Erwan Poupon and Bastien Nay


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Biomimetic Organic Synthesis

Volume 1

Alkaloids

Edited by Erwan Poupon and Bastien Nay


Biomimetic Organic Synthesis

Volume 2
Terpenoids, Polyketides, Polyphenols, Frontiers in Biomimetic
Chemistry

Edited by Erwan Poupon and Bastien Nay


The Editors
Prof. Dr. Erwan Poupon
Universit´e Paris-Sud
Facult´e du Pharmacie
5, rue Jean-Baptiste Cl´ement
92260 Chˆatenay-Malabry
France
Dr. Bastien Nay
Museum National d’Histoire
Naturelle, CNRS
57, rue Cuvier
75005 Paris
France

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V

Foreword
The beauty and diversity of the biochemical pathways developed by Nature to
produce complex molecules is a good source of inspiration for chemists who
want to guided in their synthetic approach by biomimetic strategies. The first
biomimetic syntheses were reported at the beginning of the 20th century, with the
famous examples of Collie’s and Robinson’s related to the synthesis of phenolics
(orcinol) and alkaloids (tropinone). Since then, the number of reported biomimetic
syntheses, especially in the last twenty years, has increased, demonstrating the
power of these approaches in contemporary organic and bioorganic chemistry.
Biomimetic strategies allow the construction of complex natural products in a
minimum of steps which is in accordance with the ‘‘atom economy’’ principle of
green chemistry and, in addition, simple reagents can be used to access the targets.

Furthermore, the bioorganic consequences of such successful syntheses allow
the comprehension of the biosynthetic origin of natural compounds and these
processes can produce sufficient quantities of pure products to achieve biological
investigations.
The biomimetic synthesis field came to maturity thanks to interconnexions
between biosynthetic studies and organic synthesis, especially in the total synthesis
of complex molecules. Biomimetic syntheses could even be considered as the
latest stage of biosynthetic studies, confirming or invalidating the intimate steps
leading to natural product skeletons. For example, the Johnson’s polycyclization
of squalene precursors is one of the most impressive achievements in this field.
This is still organic synthesis as the reactions are taking place in the chemist’s
flask under chemically controlled experimental conditions, while biosynthetic steps
can involve enzymatic catalysis, at least to a certain extent. However, concerning
complex biochemical transformations, the exact role of enzymes has not always
been clear, and has even been questionned by synthetic chemists.
The two book volumes ‘‘Biomimetic Organic Synthesis’’ fill the gap in the organic
chemistry literature on complex natural products. These books gather 25 chapters
from outstanding authors, not only dealing with the most important families
of natural products (alkaloids, terpenoids, polyketides, polyphenols. . .), but also
with biologically inspired reactions and concepts which are truly taking part in
biomimetic processes. By assembling these books, the editors E. Poupon and
B. Nay succeeded in gathering specialists in complex natural product chemistry


VI

Foreword

for the benefit of the synthetic chemist community. With an educational effort
in discussions and schemes, and in comparing both the biosynthetic routes and

the biomimetic achievements, the demonstration of the power of the biomimetic
strategies will become obvious to the readers in both research and teaching areas.
These books will be a great source of inspiration for organic chemists and will
ensure the continued development in this exciting field.
ESPCI-ParisTech Paris, France

Janine Cossy


VII

Contents to Volume 1
Preface XVII
List of Contributors XIX
Biomimetic Organic Synthesis: an Introduction XXIII
Bastien Nay and Erwan Poupon
Part I
1

1.1
1.1.1
1.1.2
1.1.2.1
1.1.2.2
1.1.3
1.1.4
1.1.5
1.2
1.2.1
1.2.1.1

1.2.1.2
1.2.2
1.2.2.1
1.2.2.2
1.2.2.3
1.2.3
1.2.3.1
1.2.3.2

Biomimetic Total Synthesis of Alkaloids 1

Biomimetic Synthesis of Ornithine/Arginine and Lysine-Derived
Alkaloids: Selected Examples 3
Erwan Poupon, Rim Salame, and Lok-Hang Yan
Ornithine/Arginine and Lysine: Metabolism Overview 3
Introduction: Three Important Basic Amino Acids 3
From Primary Metabolism to Alkaloid Biosynthesis 5
l-Ornithine Entry into Secondary Metabolism 5
l-Lysine Entry into Secondary Metabolism 5
Closely Related Amino Acids 6
The Case of Polyamine Alkaloids 7
Biomimetic Synthesis of Alkaloids 8
Biomimetically Related Chemistry of Ornithine- and Lysine-Derived
Reactive Units 9
Ornithine-Derived Reactive Units 9
Biomimetic Behavior of 4-Aminobutyraldehyde 9
Dimerization 10
Lysine-Derived Reactive Units 11
Oxidative Degradation of Free l-Lysine 11
Clemens Schăopf s Heritage: 50 Years of Endocyclic Enamines and

Tetrahydroanabasine Chemistry 12
Spontaneous Formation of Alkaloid Skeletons from
Glutaraldehyde 13
Biomimetic Access to Pipecolic Acids 15
Pipecolic Acids: Biosynthesis and Importance 15
Biomimetic Access to Pipecolic Acids 16


VIII

Contents

1.3
1.3.1
1.3.2
1.3.3
1.3.4
1.3.5
1.3.5.1
1.3.5.2
1.3.6
1.4
1.4.1
1.4.2
1.4.2.1
1.4.2.2
1.4.2.3
1.4.3
1.4.3.1
1.4.3.2

1.4.3.3
1.4.4
1.5
1.5.1
1.5.2
1.5.2.1
1.5.2.2
1.5.3
1.5.4
1.5.4.1
1.5.4.2
1.5.4.3
1.5.4.4
1.5.4.5
1.5.4.6
1.5.4.7
1.5.4.8

Biomimetic Synthesis of Alkaloids Derived from Ornithine and
Arginine 18
Biomimetic Access to the Pyrrolizidine Ring 18
Biomimetic Syntheses of Elaeocarpus Alkaloids 19
Biomimetic Synthesis of Fissoldhimine 22
Biomimetic Synthesis of Ficuseptine, Juliprosine, and
Juliprosopine 25
Biomimetic Synthesis of Arginine-Containing Alkaloids:
Anchinopeptolides and Eusynstyelamide A 26
Natural Products Overview 26
Biomimetic Synthesis 26
A Century of Tropinone Chemistry 29

Biomimetic Synthesis of Alkaloids Derived from Lysine 30
Alkaloids Derived from Lysine: To What Extent? 30
Lupine Alkaloids 31
Overview and Biosynthesis Key Steps 31
Biomimetic Synthesis of Lupine Alkaloids 32
A Biomimetic Conversion of N-Methylcytisine into Kuraramine 33
Biomimetic Synthesis of Nitraria and Myrioneuron Alkaloids 34
Biomimetic Syntheses of Nitraramine 35
Biomimetic Syntheses of Tangutorine 37
Endocyclic Enamines Overview: Biomimetic Observations 39
Biomimetic Synthesis of Stenusine, the Spreading Agent of Stenus
comma 39
Pelletierine-Based Metabolism 42
Pelletierine: A Small Alkaloid with a Long History 42
Biomimetic Synthesis of Pelletierine and Pseudopelletierine 43
Pelletierine (129) 43
Pseudopelletierine 44
Lobelia and Sedum Alkaloids 44
Lycopodium Alkaloids 44
Overview, Classification, and Biosynthesis 44
Biomimetic Rearrangement of Serratinine into Serratezomine A 47
Biomimetic Conversion of Serratinine into Lycoposerramine B 47
Biomimetic Interrelations within the Lycoposerramine and
Phlegmariurine Series 49
When Chemical Predisposition Does Not Follow Biosynthetic
Hypotheses: Unnatural ‘‘Lycopodium-Like’’ Alkaloids 50
Total Synthesis of Cermizine C and Senepodine G 51
Biomimetic Steps in the Total Synthesis of Fastigiatine 52
Biomimetic Steps in the Total Synthesis of Complanadine A 53
References 54

Contents

2

2.1
2.2
2.2.1
2.2.2
2.3
2.4
2.4.1
2.4.2
2.4.3

3

3.1
3.1.1
3.1.2
3.2
3.3
3.3.1
3.3.2
3.3.3
3.3.4
3.3.5
3.3.6
3.4

3.5
3.5.1
3.5.2
3.6

Biomimetic Synthesis of Alkaloids Derived from Tyrosine: The Case of
FR-901483 and TAN-1251 Compounds 61
Huan Liang and Marco A. Ciufolini
Introduction 61
Biomimetic Total Syntheses of FR-901483 and TAN-1251
Compounds 63
Snider Synthesis of FR-901483 64
Snider Synthesis of TAN-1251 Substances 67
Oxidative Amidation of Phenols 71
Biomimetic Syntheses of FR-901483 and TAN-1251 Compounds via
Oxidative Amidation Chemistry and Related Processes 77
Sorensen Synthesis of FR-901483 78
Honda Synthesis of TAN-1251 Substances 79
Ciufolini Synthesis of FR-901483 and TAN-1251C 80
References 86
Biomimetic Synthesis of Alkaloids Derived from Tryptophan:
Indolemonoterpene Alkaloids 91
Sylvie Michel and Fran¸cois Tillequin
Introduction 91
Indolemonoterpene Alkaloids 91
Classification and Botanical Distribution 91
Biomimetic Synthesis of Indolomonoterpene Alkaloids with a
Non-rearranged Monoterpene Unit: Aristotelia Alkaloids 93
Biomimetic Synthesis of Secologanin-Derived Indolomonoterpene
Alkaloids 96

Strictosidine, Vincoside, and Simple Corynanthe Alkaloids:
Heteroyohimbines and Yohimbines 96
Antirhine Derivatives 99
Conversion of the Corynanthe Skeleton into the Strychnos Skeleton 99
Fragmentation and Rearrangements of Corynanthe Alkaloids:
Ervitsine-, Ervatamine-, Olivacine-, and Ellipticine-Type Alkaloids 102
Iboga and Aspidosperma Alkaloids 106
Fragmentation and Rearrangements of Aspidosperma Alkaloids: Vinca
Alkaloids and Rhazinilam 106
Biomimetic Synthesis of Secologanin-Derived Quinoline
Alkaloids 109
Biomimetic Synthesis of Dimeric Indolomonoterpene Alkaloids 110
Anhydrovinblastine and the Anticancer Vinblastine Series 110
Strellidimine 113
Conclusion 113
References 114

IX


X

Contents

4

4.1
4.2
4.2.1
4.2.2

4.2.3
4.3
4.3.1
4.4

5
5.1
5.2
5.2.1
5.2.2
5.2.3
5.2.4
5.2.5
5.2.6
5.2.7
5.2.8
5.2.9
5.2.10
5.3

6
6.1
6.2
6.2.1
6.2.2
6.2.3
6.3

Biomimetic Synthesis of Alkaloids Derived from Tryptophan:
Dioxopiperazine Alkaloids 117

Timothy R. Welch and Robert M. Williams
Introduction 117
Prenylated Indole Alkaloids 117
Dioxopiperazines Derived from Tryptophan and Proline 119
Dioxopiperazine Derived from Tryptophan and Amino Acids other
than Proline 122
Bicyclo[2.2.2]diazaoctanes 126
Non-prenylated Indole Alkaloids 141
Epidithiodioxopiperazines 141
Conclusion 146
Acknowledgment 147
References 147
Biomimetic Synthesis of Alkaloids with a Modified Indole Nucleus 149
Tanja Gaich and Johann Mulzer
Introduction 149
Individual Examples 150
(±)-Camptothecin 150
(±)-Discorhabdins C and E 154
(±)-Brevianamides, Paraherquamides, VM55599, and
Marcfortines 155
(+)-Stephacidin A and (−)-Stephacidin B 158
(±)-Chartelline C 160
(+)-Welwitindolinone A and (−)-Fischerindole I 164
(−)-Gelselegine 166
Communesin, Calycanthines, and Chimonanthines 168
(+)-11,11 -Dideoxyverticillin A 171
(±)-Borreverine and (±)-Isoborreverine 173
Conclusion 175
References 175
Biomimetic Synthesis of Manzamine Alkaloids 181

Romain Duval and Erwan Poupon
Introduction 181
Two Complementary Hypotheses: An ‘‘Acrolein Scenario’’ and a
‘‘Malondialdehyde Scenario’’ 182
From Fatty Aldehydes Precursors to Simple 3-Alkyl-Pyridine
Alkaloids 182
Biomimetic Synthesis of Dihydropyridines and Dihydropyridinium
Salts 188
A Tool Box of Biomimetic C5 Reactive Units from the ‘‘Old’’ Zincke
Reaction 189
Biomimetic Synthesis of Pyridinium Marine Sponge Alkaloids 191


Contents

6.3.1
6.3.2
6.3.3
6.3.4
6.3.4.1
6.3.4.2
6.4
6.4.1
6.4.2
6.4.2.1
6.4.2.2
6.4.3
6.4.3.1
6.4.3.2
6.4.3.3

6.5

6.5.1
6.5.2
6.6
6.6.1
6.6.2
6.7
6.7.1
6.7.2
6.7.3
6.8
6.9
6.9.1
6.9.2
6.9.3
6.9.4
6.9.5
6.9.6
6.9.7

Biomimetic Total Synthesis of Cyclostellettamine B and Related
3-Alkylpyridiniums 191
Biomimetic Synthesis of Xestospongins and Related Structures 191
Is the Zincke-Type Pyridine Ring-Opening Biomimetic? 193
Alkylpyridines with Unusual Linking Patterns 194
Biomimetic Synthesis of Pyrinodemin A 194
Biomimetic Synthesis of Pyrinadine A 195
Development of Baldwin’s Hypothesis: From Cyclostellettamines to
Keramaphidin-Type Alkaloids 195

Linking Pyridinium Alkaloids and Manzamine A-Type Alkaloids 195
Biomimetic Total Synthesis of Keramaphidin B 197
Model Studies (1994) 197
Total Synthesis of Keramaphidin B (1998) 197
Drawbacks of the ‘‘Acrolein’’ Scenario 198
Very Low Yield of the Endo-Intramolecular Diels–Alder Reaction 198
Undesirable Transannular Hydride Transfers 199
Conversion of a ‘‘Keramaphidin’’ Skeleton into an
‘‘Ircinal/Manzamine’’ Skeleton Was Not Experimentally Possible 200
‘‘Malondialdehyde Scenario:’’ A Modified Hypothesis Placing
Aminopentadienals as Possible Precursors of Manzamine
Alkaloids 200
Keramaphidin/Ircinal Connection 200
Halicyclamine Connection 201
Testing the Modified Hypothesis in the Laboratory 203
Biomimetic Models toward Manzamine A 203
Biomimetic Models toward Halicyclamines 205
Biomimetic Approaches toward Other Manzamine Alkaloids 208
Biomimetic Models of Madangamine Alkaloids 208
Biomimetic Model of Nakadomarine A 210
Biomimetic Models of Sarains: A Side Branch of the Manzamine
Tree 211
A Biomimetic Tool-Box for the Synthesis of Manzamine Alkaloids:
Glutaconaldehydes and Aminopentadienals 213
Biosynthesis of Manzamine Alkaloids: Towards a Universal
Scenario 215
From Fatty Acids to Long-Chain Aminoaldehydes and Sarain
Alkaloids 215
Pyridine Alkaloids: Theonelladine, Cyclostellettamine, and
Xestospongin-Type Alkaloids 215

From Cyclostellettamines to Keramaphidin and
Halicyclamine/Haliclonamine Alkaloids 218
Spinal Cord of Manzamine Metabolism: The Ircinal Pathway 218
From Ircinal and Pro-ircinals to Manzamine A Alkaloids 218
From Pro-ircinals to Madangamine Alkaloids 218
From Pro-ircinals to Manadomanzamine Alkaloids 219

XI


XII

Contents

6.9.8
6.10
6.11

From Ircinals and Pro-ircinals to Nakadomarine Alkaloids 219
Total Syntheses of Manzamine-Type Alkaloids 219
Conclusion 220
References 221

7

Biomimetic Synthesis of Marine Pyrrole-2-Aminoimidazole and
Guanidinium Alkaloids 225
J´erˆome Appenzeller and Ali Al-Mourabit
Introduction 225
Introduction to Pyrrole-2-Aminoimidazole (P-2-AI) Marine

Alkaloids 226
Proposed Biogenetic Hypothesis for Clathrodin (1) and Related
Monomers Starting from -Amino Acids 229
Ground Work of George Băuchi: Dibromophakellin (7) Synthesis from
Dihydrooroidin (31) 233
Biomimetic Synthesis of P-2-AI Linear and Polycyclic
Monomers 234
Biomimetic Synthesis of Linear Monomers 237
Debromodispacamides B (18) and D (39) and Dispacamide
A (4) 237
Clathrodin (1) and Its Brominated Derivative Oroidin (3) 237
Biomimetic Synthesis of Cyclized Monomers 238
Cyclooroidin (48) 238
Dibromoagelaspongin (6) 238
Dibromophakellin (7) and Dibromophakellstatin (69) 243
Hymenialdisines (91) 247
Agelastatins 250
Biomimetic Synthesis of P-2-AIs Simple Dimers 253
Mauritiamine 253
Sceptrins, Ageliferins, and Oxysceptrins 254
Biomimetic Synthesis of Complex Dimers: Palau’amine and Related
Congeners 255
Common Chemical Pathway for P-2-AI Biosynthesis 256
First Proposal Based on a Diels–Alder Key Step 257
Universal Chemical Pathway 257
Intramolecular Aziridinium Mediated Mechanism for the Formation
of Massadine (141) from Massadine Chloride (155) 259
Aziridinium Mechanism for the Formation of the Tetramer
Stylissadine A 259
Synthetic Achievements 261

Axinellamines A/B 262
Massadine Chloride (149) and Massadine (135) 263
Palau’amine (11) 265
New Challenging P-2-AI Synthetic Targets and Perspectives 266
References 267

7.1
7.1.1
7.1.2
7.2
7.3
7.3.1
7.3.1.1
7.3.1.2
7.3.2
7.3.2.1
7.3.2.2
7.3.2.3
7.3.2.4
7.3.2.5
7.4
7.4.1
7.4.2
7.5
7.5.1
7.5.2
7.5.3
7.5.4
7.5.5
7.5.6

7.5.6.1
7.5.6.2
7.5.6.3
7.6


Contents

8
8.1
8.2
8.2.1
8.2.2
8.3
8.3.1
8.3.2
8.3.3
8.4
8.4.1
8.4.2
8.4.3
8.4.4
8.5
8.5.1
8.5.2
8.6

9

9.1

9.1.1
9.1.2
9.1.3
9.2
9.2.1
9.2.2
9.2.3
9.2.4
9.2.5
9.2.6
9.3
9.3.1
9.3.2
9.3.3
9.3.4

Biomimetic Syntheses of Alkaloids with a Non-Amino Acid Origin
Edmond Gravel
Introduction 271
Galbulimima Alkaloids 271
Alkaloids of Class I 272
Alkaloids of Class II and Class III 273
Cyclic Imine Marine Alkaloids 275
Symbioimine and Neosymbioimine 276
Pinnatoxins and Pteriatoxins 279
Gymnodimine and Derivatives 282
Other Polyketide Derived Alkaloids 284
Cassiarins A and B 284
Decahydroquinoline Alkaloids 285
Zoanthamine Alkaloids 288

Azaspiracids 291
Alkaloids Derived from Terpene Precursors 293
Cephalostatins and Ritterazines 294
Daphniphyllum Alkaloids 298
Conclusion 305
References 307
Biomimetic Synthesis of Azole- and Aryl-Peptide Alkaloids 317
Hans-Dieter Arndt, Roman Lichtenecker, Patrick Loos, and
Lech-Gustav Milroy
Introduction 317
Peptide Alkaloids: An Overview 317
Sources of Peptide Alkaloids 318
Key Features of Biosynthesis 319
Azole-Containing Peptide Alkaloids 321
Structural Features 321
Biomimetic Elements in Azole-Containing Peptide
Alkaloids 323
Thiangazole 324
Lissoclinamide 7 326
Thiostrepton 328
GE2270A 334
Peptide Alkaloids Cyclized by Oxidation of Aryl Side
Chains 336
Cyclic Peptides Containing Aryl-Alkyl Ethers 336
Cyclic Peptides Containing Biaryl Ethers 339
Cyclopeptides Containing Biaryls 344
Vancomycin 345
References 350

271

XIII


XIV

Contents

10

10.1
10.1.1
10.1.2
10.1.2.1
10.1.2.2
10.1.2.3
10.1.3
10.1.3.1
10.1.3.2
10.1.3.3
10.1.4
10.1.4.1
10.1.4.2
10.1.4.3
10.1.5
10.1.5.1
10.1.5.2
10.1.5.3
10.1.5.4
10.1.5.5

10.1.5.6
10.2
10.2.1
10.2.2
10.2.3
10.2.4
10.3

Biomimetic Synthesis of Indole-Oxidized and Complex Peptide
Alkaloids 357
Hans-Dieter Arndt, Lech-Gustav Milroy, and Stefano Rizzo
Indole-Oxidized Cyclopeptides 357
Introduction 357
TMC-95A–D 358
Formation of the Trp-Tyr Biaryl Bond by Metal-Catalyzed Cross
Coupling 361
Stereocontrolled Oxidation of the Oxindole Fragment 361
Late-Stage Stereoselective (Z)-Enamide Formation 362
Celogentin C 363
Intramolecular Knoevenagel Condensation/Radical Conjugate
Addition 366
C–H Activation–Indolylation 367
NCS-Mediated Oxidative Coupling 368
Himastatin and Chloptosin 369
Synthesis of the Himastatin Pyrroloindole Core 372
Synthesis of the Chloptosin Pyrroloindole Core 373
Macrolactamization 373
Diazonamide 375
Late-Stage Aromatic Chlorination 378
Bisoxazole Ring System via Oxidative Dehydrative Cyclization 379

Oxidative Annulation 379
Sequential Nucleophilic 1,2-Addition, Electrophilic Aromatic
Substitution 380
Reductive Aminal Formation 380
Indole–Indole Coupling 381
A Complex Peptide Alkaloid: Ecteinascidine 743 (ET 743) 382
Biosynthesis and Biomimetic Strategy 383
Pentacycle Formation 385
Bridge Formation 389
Endgame 390
Outlook 391
References 392

Contents to Volume 2
Part II
Biomimetic Synthesis of Terpenoids and Polyprenylated
Natural Compounds 395
11

Biomimetic Rearrangements of Complex Terpenoids 397
Bastien Nay and Laurent Evanno


Contents

12

Polyprenylated Phloroglucinols and Xanthones 433
Marianna Dakanali and Emmanuel A. Theodorakis
Part III

Biomimetic Synthesis of Polyketides

469

13

Polyketide Assembly Mimics and Biomimetic Access to Aromatic
Rings 471
Gr´egory Genta-Jouve, Sylvain Antoniotti, and Olivier P. Thomas

14

Biomimetic Synthesis of Non-Aromatic Polycyclic Polyketides 503
Bastien Nay and Nassima Riache

15

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide
Opening 537
Ivan Vilotijevic and Timothy F. Jamison

16

Biomimetic Electrocyclization Reactions toward Polyketide-Derived
Natural Products 591
James Burnley, Michael Ralph, Pallavi Sharma, and John E. Moses
Part IV

Biomimetic Synthesis of Polyphenols 637

17

Biomimetic Synthesis and Related Reactions of Ellagitannins 639
Takashi Tanaka, Isao Kouno, and Gen-ichiro Nonaka

18

Biomimetic Synthesis of Lignans 677
Craig W. Lindsley, Corey R. Hopkins, and Gary A. Sulikowski

19

Synthetic Approaches to the Resveratrol-Based Family of Oligomeric
Natural Products 695
Scott A. Snyder

20

Sequential Reactions Initiated by Oxidative Dearomatization.
Biomimicry or Artifact? 723
Stephen K. Jackson, Kun-Liang Wu, and Thomas R.R. Pettus
Part V
Frontiers in Biomimetic Chemistry: From Biological to
Bio-inspired Processes 751

21

The Diels–Alderase Never Ending Story
Atsushi Minami and Hideaki Oikawa

753

22

Bio-Inspired Transfer Hydrogenations 787
Magnus Rueping, Fenja R. Schoepke, Iuliana Atodiresei, and Erli Sugiono

XV


XVI

Contents

23

Life’s Single Chirality: Origin of Symmetry Breaking in
Biomolecules 823
Michael Mauksch and Svetlana B. Tsogoeva
Part VI

24

Conclusion: From Natural Facts to Chemical Fictions 847

Artifacts and Natural Substances Formed Spontaneously 849
Pierre Champy
Index 935

XVII

Preface
When we decided to start this project, at the end of 2008, we were perfectly aware
that the amount of work to provide on it, the Biomimetic Organic Synthesis saga,
would be very important. In fact, we were far from reality since the field not only
concerns the huge universe of natural product chemistry, but also tends to embrace
many fields beyond. We tried to design this book according to natural product
chemistry principles, mainly by compound classes, and hope that few of them
slipped our notice. Hopefully, the contributors who were asked to write a chapter
in their respective field have welcomed this project with a great enthusiasm and
worked hard to finish their chapter on time. Our editing adventure is now ending
and we want now to warmly thank all of them for their outstanding contribution to
this lengthy book. We also want to pay tribute to Professor Franc¸ois Tillequin, so
happy with natural product chemistry, who recently passed away. Special thanks
are also due to the staff of Wiley-VCH especially to Dr Gudrun Walter and Lesley
Belfit for excellent collaboration.
Biomimetic synthesis is the construction of natural products by chemical means
using Nature’s hypothetical or established strategies, i.e. starting from synthetic
mimicry of Nature’s biosynthetic precursors, ideally by way of biologically compatible reactions. In theory, this principle can be applied to all natural product
classes, from the simplest to the most complex compounds. Yet the activation
methods in the laboratory can be far from Nature’s enzymatic environment, and
the biomimetic step can then be more difficult than expected at first glance. The way
may therefore be tricky, even for a skilled chemist. We hope this book will delight
readers by materializing most of organic synthesis concepts built from biochemical
(biosynthetic) inspirations. Fortunately, readers may find solutions to synthetic
problems or, at least, find a new way to improve their knowledge, as we did.
Enjoy reading.
March 2011

Erwan Poupon
Universit´e Paris-Sud, Chˆatenay-Malabry, France
Bastien Nay
Mus´eum National d’Histoire Naturelle, Paris, France


XIX

List of Contributors
Ali Al-Mourabit
Centre de Recherche de
Gif-sur-Yvette
Institut de Chimie des
Substances Naturelles
UPR 2301 CNRS
Avenue de la Terrasse
91198 Gif-sur-Yvette
France
J´erˆome Appenzeller
Centre de Recherche de
Gif-sur-Yvette
Institut de Chimie des
Substances Naturelles
UPR 2301 CNRS
Avenue de la Terrasse
91198 Gif-sur-Yvette
France
Hans-Dieter Arndt
Technische Universităat

Dortmund
Fakultăat Chemie
Otto-Hahn-Strasse 6
44221 Dortmund
Germany
and

Max-Planck Institut făur
Molekulare Physiologie
Otto-Hahn-Strasse 11
44227 Dortmund
Germany
Marco A. Ciufolini
The University of
British Columbia
Department of Chemistry
2036 Main Mall
Vancouver
British Columbia V6T 1Z1
Canada
Romain Duval
Institut de Recherche pour le
D´evelopement
UMR 152
Facult´e des Sciences
Pharmaceutiques
118 Route de Narbonne
31062 Toulouse
France
Tanja Gaich

Leibniz Universităat Hannover
Institute of Organic Chemistry
Schneiderberg 1
30167 Hannover
Germany


XX

List of Contributors

Edmond Gravel
CEA, iBiTecS
Service de Chimie
Bioorganique et de Marquage
91191 Gif-sur-Yvette
France
Huan Liang
The University of
British Columbia
Department of Chemistry
2036 Main Mall
Vancouver
British Columbia V6T 1Z1
Canada
Roman Lichtenecker
Technische Universităat
Dortmund
Fakultăat Chemie
Otto-Hahn-Strasse 6

44221 Dortmund
Germany

Max-Planck Institut făur
Molekulare Physiologie
Otto-Hahn-Strasse 11
44227 Dortmund
Germany
Sylvie Michel
Universit´e Paris Descartes
Facult´e de Pharmacie
Laboratoire de Pharmacognosie
U.M.R.-C.N.R.S. n◦ 8638
4 Avenue de lObservatoire
75006 Paris
France
Lech-Gustav Milroy
Technische Universităat
Dortmund
Fakultăat Chemie
Otto-Hahn-Strasse 6
44221 Dortmund
Germany
and

and
Max-Planck Institut făur
Molekulare Physiologie
Otto-Hahn-Strasse 11
44227 Dortmund

Germany
Patrick Loos
Technische Universităat
Dortmund
Fakultăat Chemie
Otto-Hahn-Strasse 6
44221 Dortmund
Germany
and

Max-Planck Institut făur
Molekulare Physiologie
Otto-Hahn-Strasse 11
44227 Dortmund
Germany
Johann Mulzer
University of Vienna
Institute of Organic Chemistry
Wăahringer Strasse 38
1090 Vienna
Austria
Erwan Poupon
Universite Paris-Sud 11
Faculte de Pharmacie
5 rue Jean-Baptiste Cl´ement
92260 Chˆatenay-Malabry
France


List of Contributors

Stefano Rizzo
Technische Universităat
Dortmund
Fakultăat Chemie
Otto-Hahn-Strasse 6
44221 Dortmund
Germany
and
Max-Planck Institut făur
Molekulare Physiologie
Otto-Hahn-Strasse 11
44227 Dortmund
Germany
Rim Salame
Universit´e Paris-Sud 11
Facult´e de Pharmacie
5 rue Jean-Baptiste Cl´ement
92260 Chˆatenay-Malabry
France
Franc¸ois Tillequin
Universit´e Paris Descartes
Facult´e de Pharmacie
Laboratoire de Pharmacognosie
U.M.R.-C.N.R.S. n◦ 8638
4 Avenue de l’Observatoire
75006 Paris
France

Timothy R. Welch

Colorado State University
Department of Chemistry
Fort Collins, CO 80523-1872
USA
Robert M. Williams
Colorado State University
Department of Chemistry
Fort Collins, CO 80523-1872
USA
Lok-Hang Yan
Universit´e Paris-Sud 11
Facult´e de Pharmacie
5 rue Jean-Baptiste Cl´ement
92260 Chˆatenay-Malabry
France

XXI


XIX

List of Contributors
Sylvain Antoniotti
Universit´e de
Nice-Sophia Antipolis
Facult´e des Sciences
D´epartment de Chimie
28 AvenueValrose
06108 Nice Cedex 2
France

Iuliana Atodiresei
RWTH Aachen University
Institute of Organic Chemistry
Landoltweg 1
52074 Aachen
Germany
James Burnley
University of Nottingham
Faculty of Science
School of Chemistry
University Park
Nottingham NG7 2RD
United Kingdom

Pierre Champy
Universit´e Paris-Sud 11
Chimie des Substances
Naturelles CNRS
UMR 8076 BioCIS
Facult´e de Pharmacie
5 rue Jean-Baptiste Cl´ement
92296 Chˆatenay-Malabry
France
Marianna Dakanali
University of California
San Diego
Department of Chemistry and
Biochemistry
9500 Gilman Drive
La Jolla

San Diego, CA 92093-0358
USA
Laurent Evanno
Mus´eum National
d’Histoire Naturelle
Unit´e Mol´ecules de
Communication et Adaptation
des Micro-organismes associ´ee au
CNRS (UMR 7245)
57 rue Cuvier
75005 Paris
France


XX

List of Contributors

Gr´egory Genta-Jouve
Universit´e de
Nice-Sophia Antipolis
Facult´e des Sciences
D´epartment de Chimie
28 AvenueValrose
06108 Nice Cedex 2
France
Corey R. Hopkins
Vanderbilt University
Medical Center
Department of Chemistry

Department of Pharmacology
Vanderbilt Program in Drug
Discovery
Nashville, TN 37272-6600
USA
Stephen K. Jackson
University of California
Department of Chemistry
and Biochemistry
Santa Barbara, CA 93106-9510
USA
Timothy F. Jamison
Massachusetts
Institute of Technology
Department of Chemistry
77 Massachusetts Avenue
Cambridge, MA 02139
USA

Isao Kouno
Nagasaki University
Graduate School of
Biomedical Sciences
Department of Molecular
Medicinal Sciences
1-14 Bunkyo-machi
Nagasaki 852-8521
Japan
Craig W. Lindsley
Vanderbilt University

Medical Center
Department of Chemistry
Department of Pharmacology
Vanderbilt Program in
Drug Discovery
Nashville, TN 37272-6600
USA
Michael Mauksch
University of
Erlangen- Nuremberg
Department of Chemistry
and Pharmacy
Henkestrasse 42
91054 Erlangen
Germany
Atsushi Minami
Hokkaido University
Graduate School of Science
Division of Chemistry
Sapporo 060-0810
Japan


List of Contributors

John E. Moses
University of Nottingham
Faculty of Science
School of Chemistry
University Park

Nottingham NG7 2RD
United Kingdom

Michael Ralph
University of Nottingham
Faculty of Science
School of Chemistry
University Park
Nottingham NG7 2RD
United Kingdom

Bastien Nay
Mus´eum National
d’Histoire Naturelle
Unit´e Mol´ecules de
Communication et Adaptation
des Micro-organismes associ´ee au
CNRS (UMR 7245)
57 rue Cuvier
75005 Paris
France

Nassima Riache
Mus´eum National
d’Histoire Naturelle
Unit´e Mol´ecules de
Communication et Adaptation
des Micro-organismes associ´ee au
CNRS (UMR 7245)
57 rue Cuvier

75005 Paris
France

Gen-ichiro Nonaka
Usaien Pharmaceutical Company
Ltd. 1-4-6 Zaimoku
Saga 840-0055
Japan

Magnus Rueping
RWTH Aachen University
Institute of Organic Chemistry
Landoltweg 1
52074 Aachen
Germany

Hideaki Oikawa
Hokkaido University
Graduate School of Science
Division of Chemistry
Sapporo 060-0810
Japan
Thomas R.R. Pettus
University of California
Department of Chemistry
and Biochemistry
Santa Barbara, CA 93106-9510
USA

Fenja R. Schoepke

RWTH Aachen University
Institute of Organic Chemistry
Landoltweg 1
52074 Aachen
Germany
Pallavi Sharma
University of Nottingham
Faculty of Science
School of Chemistry
University Park
Nottingham NG7 2RD
United Kingdom

XXI