Chemical Synthesis of Nucleoside Analogues

Compiles current tested and proven approaches tosynthesize novel nucleoside analogues

Featuring contributions from leading synthetic chemists fromaround the world, this book brings together and describes testedand proven approaches for the chemical synthesis of common familiesof nucleoside analogues. Readers will learn to create newnucleoside analogues with desired therapeutic properties by using avariety 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– orheterocyclic ring Introduction of conformational restrictions Synthesis of enantiomers Preparation of hydrolitically stable C–nucleosides

Chemical Synthesis of Nucleoside Analogues covers all themajor classes of nucleosides, including pronucleotides,C–nucleosides, carbanucleosides, and PNA monomers which have showngreat promise as starting points for the synthesis of nucleosideanalogues. The book also includes experimental procedures for keyreactions related to the synthesis of nucleoside analogues,providing a valuable tool for the preparation of a number ofdifferent compounds.

Throughout the book, chemical schemes and figures help readersbetter understand the chemical structures of nucleoside analoguesand the methods used to synthesize them. Extensive references serveas a gateway to the growing body of original research studies andreviews in the field.

Synthetically modified nucleosides have proven their value astherapeutic drugs, in particular as antiviral and antitumor agents.However, many of these nucleoside analogues have undesirable sideeffects. With Chemical Synthesis of Nucleoside Analogues astheir guide, researchers have a new tool for synthesizing a newgeneration of nucleoside analogues that can be used as therapeuticdrugs with fewer unwanted side effects.

Contributors ix

Foreword xiii

Preface xv

1 Biocatalytic Methodologies for Selective Modified Nucleosides1
Miguel Ferrero, Susana Fern´andez, and VicenteGotor

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–RongQu

4 Phosphonated Nucleoside Analogues 163
Roberto Romeo, Caterina Carnovale, Antonio Rescifina, and MariaAssunta 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, andSergio Castill´on

8 Methodologies for the Synthesis of Isomeric Nucleosides andNucleotides of Antiviral Significance 317
Maurice Okello and Vasu Nair

9 Synthesis of Conformationally Constrained Nucleoside Analogues345
Esma Maougal, Jean–Marc Escudier, Christophe Len, DidierDubreuil, and Jacques Lebreton

10 Synthesis of 3–Spiro–Substituted Nucleosides: Chemistry ofTSAO Nucleoside Derivatives 427
Mar´ýa–Jos´e Camarasa, Sonsoles Vel´azquez,Ana San–F´elix, and Mar´ýa–Jes´usP´erez–P´erez

11 l–Nucleosides 473
Daniela Perrone and Massimo L. Capobianco

12 Chemical Synthesis of Carbocyclic Analogues of Nucleosides535
E. Leclerc

13 Uncommon Three–, Four–, and Six–Membered Nucleosides605
E. Groaz and P. Herdewijn

14 Recent Advances in Synthesis and Biological Activity of4–Thionucleosides 655
Varughese A. Mulamoottil, Mahesh S. Majik, Girish Chandra, andLak Shin Jeong

15 Recent Advances in the Chemical Synthesis of Aza–Nucleosides699
Tom´as Tejero, Ignacio Delso, and Pedro Merino

16 Stereoselective Methods in the Synthesis of BioactiveOxathiolane and Dioxolane Nucleosides 727
D. D Alonzo and A. Guaragna

17 Isoxazolidinyl Nucleosides 781
Ugo Chiacchio, Antonino Corsaro, Salvatore Giofr`e, and GiovanniRomeo

18 Synthetic Studies on Antifungal Peptidyl NucleosideAntibiotics 819
Apurba Datta

19 Chemical Synthesis of Conformationally Constrained PNAMonomers 847
Pedro Merino and Rosa Matute

Index 881

PEDRO MERINO, PhD, is the Director of the Department ofSynthesis and Structure of Biomolecules of the Institute ofChemical Synthesis and Homogenous Catalysis at the University ofZaragoza. Dr. Merino has authored more than 200 publications,including several reviews and book chapters. His research spansasymmetric synthesis, target–oriented synthesis, organometallicchemistry, and asymmetric metal–assisted and organic catalysis.Recently, he has been investigating the use of computationalchemistry to better understand reaction mechanisms.