Modern Tools for the Synthesis of Complex Bioactive Molecules

All the latest tools needed to plan and perform the synthesisof complex bioactive molecules

Focusing on organic, organometallic, and bio–oriented processes,this book explores the impact and use of the latest synthetic toolsfor the synthesis of complex biologically active compounds. Readerswill discover step by step how these synthetic tools have providednew, elegant solutions to many synthetic puzzles. Moreover, theywill discover innovative methods that make it possible to controlthe exact connectivity of atoms within a molecule in order to setprecise three–dimensional arrangements.

Modern Tools for the Synthesis of Complex BioactiveMolecules features sixteen chapters, each one written by one ormore leading experts in organic synthesis from around the world. Itcovers a broad range of topics that enable readers to takeadvantage of the latest methods for synthesizing complex molecules,including:

Modern catalysis, emphasizing key transformations such as C–Hfunctionalizations, cross–couplings, gold–catalyzed reactions,metathesis–based syntheses, and asymmetric organocatalysis Eco–compatible transformations, including rearrangements anddomino reactions Tools for the synthesis of carbohydrates and alkaloids New techniques, including the use of fluorous tags andengineered biosynthesis

The last two chapters explore target– and diversity–orientedorganic synthesis as well as the use of DNA–based asymmetriccatalysis, which are all promising tools for the successfulsynthesis of complex bioactive molecules.

Modern Tools for the Synthesis of Complex BioactiveMolecules is ideal for students and researchers who need toplan and perform the synthesis of complex molecules as efficientlyas possible. The book′s expert advice will help these readersquickly resolve a broad range of problems that can arise in organicsyntheses.

FOREWORD vii

PREFACE ix

CONTRIBUTORS xi

CHAPTER 1 C H FUNCTIONALIZATION: A NEW STRATEGY FOR THESYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS 1
Sophie Rousseaux, Benoý t Lie´gault, and KeithFagnou

CHAPTER 2 THE NEGISHI CROSS–COUPLING IN THE SYNTHESIS OF NATURALPRODUCTS AND BIOACTIVE MOLECULES 33
Evelina Colacino, Jean Martinez, and Fre´de´ricLamaty

CHAPTER 3 METAL–CATALYZED C HETEROATOM CROSS–COUPLINGREACTIONS 77
Renata Marcia de Figueiredo, Jean Marc Campagne, and DamienPrim

CHAPTER 4 GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURALPRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS 111
Fabien Gagosz

CHAPTER 5 METATHESIS–BASED SYNTHESIS OF COMPLEX BIOACTIVES155
Jean–Alexandre Richard, Sin Yee Ng, and David Y.–K. Chen

CHAPTER 6 ENANTIOSELECTIVE ORGANOCATALYSIS: A POWERFUL TOOL FORTHE SYNTHESIS OF BIOACTIVE MOLECULES 189
Mitsuru Shoji and Yujiro Hayashi

CHAPTER 7 ASYMMETRIC PHASE–TRANSFER CATALYSIS 213
Seiji Shirakawa, Shin A. Moteki, and Keiji Maruoka

CHAPTER 8 REARRANGEMENTS IN NATURAL PRODUCT SYNTHESIS 243
Jose´ Marco–Contelles and Elena Soriano

CHAPTER 9 DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OFBIOACTIVE NATURAL PRODUCTS 271
Lutz F. Tietze, Scott G. Stewart, and AlexanderDu¨fert

CHAPTER 10 FLUOROUS LINKER–FACILITATED SYNTHESIS OF BIOLOGICALLYINTERESTING MOLECULES 335
Wei Zhang

CHAPTER 11 THE EVOLUTION OF IMMOBILIZED REAGENTS AND THEIRAPPLICATION IN FLOW CHEMISTRY FOR THE SYNTHESIS OF NATURAL PRODUCTSAND PHARMACEUTICAL COMPOUNDS 359
Rebecca M. Myers, Kimberley A. Roper, Ian R. Baxendale, andSteven V. Ley

CHAPTER 12 SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES395
Xavier Guinchard, Se´bastien Picard, and DavidCrich

CHAPTER 13 AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOIDSYNTHESIS 433
Scott Bur and Albert Padwa

CHAPTER 14 PRECURSOR–DIRECTED BIOSYNTHESIS OF POLYKETIDE ANDNONRIBOSOMAL PEPTIDE NATURAL PRODUCTS 485
Colin J. B. Harvey and Chaitan Khosla

CHAPTER 15 TARGET–ORIENTED AND DIVERSITY–ORIENTED ORGANICSYNTHESIS 513
Raphae¨l Rodriguez

CHAPTER 16 DNA AS A TOOL FOR MOLECULAR DISCOVERY 539
Michael Smietana, Jean–Jacques Vasseur, Janine Cossy, andStellios Arseniyadis

INDEX 557

JANINE COSSY graduated from the University of Reimsworking under the supervision of Prof. Jean–Pierre Pète. Aftera postdoctoral stay with Prof. Barry Trost (1980–1982) at theUniversity of Wisconsin, she returned to Reims where she becameDirector of Research of the CNRS in 1990. The same year, she movedto Paris to become Professor of Organic Chemistry at the EcoleSupérieure de Physique et de Chimie Industrielles de la Villede Paris (ESPCI ParisTech). She has published over 380 articles andfiled thirteen patents in the field of synthetic organic chemistryand natural product synthesis. She is Associate Editor atOrganic Letters since 2005.

STELLIOS ARSENIYADIS was born in Greece in 1975. Hestudied chemistry at the Université Paris XI and received hisPhD in 2002 from the Université Louis Pasteur (Strasbourg,France) working under the guidance of Dr. Charles Mioskowski. In2001, he joined Rhodia ChiRex (Boston, USA) for an eighteen–monthinternship in collaboration with Prof. Stephen L. Buchwald (MIT,USA). He then spent a year as a postdoctoral fellow at ImperialCollege London (UK) working under the supervision of Prof. Alan C.Spivey, after which he joined Prof. K. C. Nicolaou′s group at TheScripps Research Institute (La Jolla, USA) for an additionalpostdoc. In 2005, he was appointed by the CNRS as Chargé deRecherche in Prof. Janine Cossy′s group. His research interestsinclude the development of new synthetic tools and theirapplication to the total synthesis of complex natural products.