Emphasizing synthetic strategy and practice, Stereoselective Synthesis of Drugs and Natural Products features experimental procedures for stereoselective synthetic reactions applicable to drug targets and natural products. Compiling material from leading contributors into one cohesive resource, this practical resource on synthetic methodology, reaction mechanisms, and applications for medicinal chemistry and drug discovery explores strategy and interdisciplinary work, laboratory synthesis for natural products, the preparative aspects of stereoselective synthesis for drugs, natural products, and potential biologically active compounds. The text also features experimental procedures for the different reaction methods covered.

Preface

List of contributors

List of symbols and abbreviations

PART 1: GENERAL METHODS AND STRATEGIES

Chapter 1: Principles, concepts and strategies of stereoselective synthesis
Vasyl Andrushko and Natalia Andrushko

Chapter 2: Chiral auxiliaries in drug synthesis
Stanley Chang, Shira D. Halperin, Jarod Moore and Robert Britton

Chapter 3: Solid-phase organic synthesis of drugs and natural products
Peter J. H. Scott

Chapter 4: Asymmetric phase-transfer catalysis
Kohsuke Ohmatsu, Daisuke Uraguchi, and Takashi Ooi

Chapter 5: Microwave-assisted stereoselective synthesis
Yoann Coquerel, Evelina Colacino, Jean Rodriguez, Jean Martinez and Frédéric Lamaty

Chapter 6: Application of micro reactor methodology for organic synthesis
Paul Watts and Charlotte Wiles

PART 2: STEREOSELECTIVE SYNTHESIS BY BOND FORMATION

2.1. STEREOSELECTIVE METHODS FOR C–C BOND FORMATION

Chapter 7: Asymmetric α-alkylation of aldehydes, ketones and carboxylic acids
Mark C. Kohler, Sarah E. Wengryniuk, and Don M. Coltart

Chapter 8: Asymmetric aldol reactions in the total syntheses of natural products
Seijiro Hosokawa

Chapter 9: Asymmetric Michael addition and related reactions
Pengfei Li, Jun Wang and Fuk Yee Kwong

Chapter 10: Construction of polypropionate fragments in natural product synthesis
Maris Turks, Sylvain Laclef and Pierre Vogel

Chapter 11: Organocatalytic conjugate addition in stereoselective synthesis
Adrien Quintard and Alexandre Alexakis

Chapter 12: Stereoselective Nozaki-Hiyama-Kishi reaction
Pat Guiry and Gráinne Hargaden

Chapter 13: Transition-metal-catalyzed asymmetric C–C cross-couplings in stereoselective synthesis Vasiliki Sarli

Chapter 14: Asymmetric hydroformylation, hydroxy- and alkoxycarbonylation for stereoselective synthesis
Jamie T. Durrani and Matthew L. Clarke

Chapter 15: Intramolecular oxycarbonylation in stereoselective synthesis
Tibor Gracza

Chapter 16: Stereoselective cycloaddition reactions
Tae-Kyung Lee and Jung-Mo Ahn

Chapter 17: Sigmatropic rearrangements in stereoselective synthesis
Brinton Seashore-Ludlow and Peter Somfai

Chapter 18: Ring contraction reactions in the total synthesis of biologically active natural products
Luiz F. Silva Jr.

Chapter 19: Electrocyclic reactions in stereoselective synthesis
Marcus A. Tius

Chapter 20: Transannular cyclization in natural product total synthesis
Jiong Yang and Haoran Xue

Chapter 21: Cascade reactions in stereoselective synthesis
Bor-Cherng Hong and Nitin S. Dange

Chapter 22: Sulfur dioxide: a powerful tool for the stereoselective construction of C-C bonds
Pierre Vogel, Dean Markovic and Mâris Turks

Chapter 23: Transition metal C-H activation: application to stereoselective synthesis of natural products and drugs
Mickaël Jean and Pierre van de Weghe

Chapter 24: Metathesis reactions in drug and natural product synthesis
Akio Saito, Yuji Hanzawa

Chapter 25: Radicals in stereoselective C-C bond formation
Josep Bonjoch, Ben Bradshaw and Faïza Diaba

Chapter 26: Trifluoromethyl (CF3) group insertion methods in stereoselective synthesis
Tsutomu Konno

Chapter 27: Stereoselective organocatalyzed C–C bond-forming reactions
Kazuo Nagasawa and Koji Yasui

Chapter 28: Enzyme-catalysed stereoselective C–C bond formation reactions in total syntheses
Adeline Ranoux and Ulf Hanefeld

2.2. STEREOSELECTIVE METHODS FOR C–H BOND FORMATION

Chapter 29: Stereoselective hydrogenation of C=C bonds: application to drug and natural product synthesis
Natalia Andrushko and Vasyl Andrushko

Chapter 30: Asymmetric hydrogenation of C=O and C=N bonds in stereoselective synthesis
Natalia Andrushko and Vasyl Andrushko

Chapter 31: Asymmetric protonation of carbanions and polar double bonds: application to total syntheses
Thomas Poisson and Shu Kobayashi

Chapter 32: Organocatalytic reduction in stereoselective synthesis
Felix Kortmann and Adriaan Minnaard

Chapter 33: Biocatalytic asymmetric reduction of C=O and activated C=C bonds in stereoselective synthesis
Tomoko Matsuda, Rio Yamanaka and Kaoru Nakamura

2.3. STEREOSELECTIVE METHODS FOR C–O BOND FORMATION

Chapter 34: Transition-metal-catalyzed stereoselective oxidations in drug and natural product synthesis
Alessandro Scarso and Giorgio Strukul

Chapter 35: Asymmetric epoxidation in stereoselective synthesis
Zhicai Yang

Chapter 36: Biocatalytic asymmetric oxidations in stereoselective synthesis
Anett Schallmey, Pablo Dominguez de Maria and Paula Bracco

Chapter 37: Ether transfer methodology: application to the synthesis of polyketide natural products
Eric Stefan and Richard E. Taylor

Chapter 38: Stereoselective formation of 2-deoxyglycosidic bonds in biologically active natural products
Daisuke Takahashi and Kazunobu Toshima

2.4. STEREOSELECTIVE METHODS FOR C–N BOND FORMATION

Chapter 39: Asymmetric hydroamination and reductive amination in total synthesis
Manas K. Ghorai, Deo Prakash Tiwari and Aditya Bhattacharyya

Chapter 40: Carboamination and alkylative cyclization with C-N bond formation in stereoselective syntheses
Manas K. Ghorai, Sandipan Halder and Sauvik Samanta

Chapter 41: Cycloadditions with stereoselective C-N bond formation in total syntheses
Guillaume Vincent

2.5. STEREOSELECTIVE FORMATION OF OTHER C–HETEROATOM AND OTHER BONDS

Chapter 42: Stereoselective halogenations
Chong Kiat Tan, Yi Zhao, Jing Zhou and Ying-Yeung Yeung

Chapter 43: Stereoselective synthesis of halogenated natural products
Takehiko Yoshimitsu

Chapter 44: Asymmetric fluorination methods: application in the stereoselective synthesis of fluorinated drugs
Vincent Bizet and Dominique Cahard

Chapter 45: Enzymatic halogenation in stereoselective synthesis
Cormac D. Murphy and Benjamin R. Clark

Chapter 46: Stereoselective carbon–sulfur (C–S) bond formation
Kyungsoo Oh

Chapter 47: Stereoselective methods for carbon-phosphorus (C–P) bond formation
Marcin Kalek and Jacek Stawinski

Chapter 48: Transition-metal-catalyzed asymmetric sulfoxidation in drug and natural product synthesis
Alessandro Scarso and Giorgio Strukul

PART 3: METHODS OF ANALYSIS AND CHIRAL SEPARATION

Chapter 49: NMR-Spectroscopy in drug and natural product analysis
Stanisuaw Witkowski and Iwona Wawer

Chapter 50: Determination of enantiomeric purity and absolute configuration by NMR spectroscopy
Thomas J. Wenzel

Chapter 51: Solid-state NMR spectroscopy in drug design and discovery
David A. Middleton and Simon G. Patching

Chapter 52: Capillary electrophoresis in chiral separations
Ans Hendrickx, Debby Mangelings and Yvan Vander Heyden

Chapter 53: Determination of absolute configuration using chiroptical methods
Joao Marcos Batista, Jr.

Chapter 54: Chiral chromatographic methods in the analysis and purification of enantiomers
Arnau Novell and Cristina Minguillón

Chapter 55: X-Ray crystallography and 1H NMR anisotropy methods for determination of absolute configurations
Nobuyuki Harada

Chapter 56: Crystallization based separation of enantiomers
Yaling Wang and Alex Chen

Chapter 57: Enzymatic dynamic kinetic resolution in stereoselective synthesis
Francisca Rebolledo, Javier González-Sabín, and Vicente Gotor

Subject index