Chemical Synthesis of Nucleoside Analogues

Compiles current tested and proven approaches to synthesize novel nucleoside analogues Featuring contributions from leading synthetic chemists from around the world, this book brings together and describes tested and proven approaches for the chemical synthesis of common families of nucleoside analogues. Readers will learn to create new nucleoside analogues with desired therapeutic properties by using a variety of methods to chemically modify natural nucleosides, including: Changes to the heterocyclic base Modification of substituents at the sugar ring Replacement of the furanose ring by a different carbo- or heterocyclic ring Introduction of conformational restrictions Synthesis of enantiomers Preparation of hydrolitically stable C-nucleosides Chemical Synthesis of Nucleoside Analogues covers all the major classes of nucleosides, including pronucleotides, C-nucleosides, carbanucleosides, and PNA monomers which have shown great promise as starting points for the synthesis of nucleoside analogues. The book also includes experimental procedures for key reactions related to the synthesis of nucleoside analogues, providing a valuable tool for the preparation of a number of different compounds. Throughout the book, chemical schemes and figures help readers better understand the chemical structures of nucleoside analogues and the methods used to synthesize them. Extensive references serve as a gateway to the growing body of original research studies and reviews in the field. Synthetically modified nucleosides have proven their value as therapeutic drugs, in particular as antiviral and antitumor agents. However, many of these nucleoside analogues have undesirable side effects. With Chemical Synthesis of Nucleoside Analogues as their guide, researchers have a new tool for synthesizing a new generation of nucleoside analogues that can be used as therapeutic drugs with fewer unwanted side effects.

Contributors ix Foreword xiii Preface xv 1 Biocatalytic Methodologies for Selective Modified Nucleosides 1 Miguel Ferrero, Susana Fern´andez, and Vicente Gotor 2 Nucleosides Modified at the Base Moiety 49 O. Sari, V. Roy, and L. A. Agrofoglio 3 Chemical Synthesis of Acyclic Nucleosides 103 Hai-Ming Guo, Shan Wu, Hong-Ying Niu, Ge Song, and Gui-Rong Qu 4 Phosphonated Nucleoside Analogues 163 Roberto Romeo, Caterina Carnovale, Antonio Rescifina, and Maria Assunta Chiacchio 5 Chemical Syntheses of Nucleoside Triphosphates 209 Lina Weinschenk and Chris Meier 6 Mononucleotide Prodrug Synthetic Strategies 229 Suzanne Peyrottes and Christian P´erigaud 7 Synthesis of C-Nucleosides 263 Omar Boutureira, M. Isabel Matheu, Yolanda D´ýaz, and Sergio Castill´on 8 Methodologies for the Synthesis of Isomeric Nucleosides and Nucleotides of Antiviral Significance 317 Maurice Okello and Vasu Nair 9 Synthesis of Conformationally Constrained Nucleoside Analogues 345 Esma Maougal, Jean-Marc Escudier, Christophe Len, Didier Dubreuil, and Jacques Lebreton 10 Synthesis of 3-Spiro-Substituted Nucleosides: Chemistry of TSAO Nucleoside Derivatives 427 Mar´ýa-Jos´e Camarasa, Sonsoles Vel´azquez, Ana San-F´elix, and Mar´ýa-Jes´us P´erez-P´erez 11 l-Nucleosides 473 Daniela Perrone and Massimo L. Capobianco 12 Chemical Synthesis of Carbocyclic Analogues of Nucleosides 535 E. Leclerc 13 Uncommon Three-, Four-, and Six-Membered Nucleosides 605 E. Groaz and P. Herdewijn 14 Recent Advances in Synthesis and Biological Activity of 4-Thionucleosides 655 Varughese A. Mulamoottil, Mahesh S. Majik, Girish Chandra, and Lak Shin Jeong 15 Recent Advances in the Chemical Synthesis of Aza-Nucleosides 699 Tom´as Tejero, Ignacio Delso, and Pedro Merino 16 Stereoselective Methods in the Synthesis of Bioactive Oxathiolane and Dioxolane Nucleosides 727 D. D’Alonzo and A. Guaragna 17 Isoxazolidinyl Nucleosides 781 Ugo Chiacchio, Antonino Corsaro, Salvatore Giofr`e, and Giovanni Romeo 18 Synthetic Studies on Antifungal Peptidyl Nucleoside Antibiotics 819 Apurba Datta 19 Chemical Synthesis of Conformationally Constrained PNA Monomers 847 Pedro Merino and Rosa Matute Index 881