Divergent Synthesis and Biological Evaluation of Carbocyclic α-, iso- and 3′-epi-Nucleosides and their Lipophilic Nucleotide Prodrugs

Olaf R. Ludek; Tobias Krämer; Jan Balzarini; Chris Meier

doi:10.1055/s-2006-926411

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Synthesis 2006(8): 1313-1324
DOI: 10.1055/s-2006-926411

PAPER

Divergent Synthesis and Biological Evaluation of Carbocyclic α-, iso- and 3′-epi-Nucleosides and their Lipophilic Nucleotide Prodrugs

Olaf R. Ludek^a, Tobias Krämer^a, Jan Balzarini^b, Chris Meier*^a
^a Institut für Organische Chemie, Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Fax: +49(40)428382495; e-Mail: chris.meier@chemie.uni-hamburg.de;
^b Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium

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Publication History

Received 26 September 2005
Publication Date:
27 March 2006 (online)

Abstract
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Abstract

A new divergent approach towards carbocyclic α-, iso- and 3′-epi-nucleosides starting from enantiomerically pure (1S,2R)-2-benzyloxymethylcyclopent-3-enol (5) is described. In the key step, isomeric cyclopentanols were condensed with a N3-protected pyrimidine nucleobase using a modified Mitsunobu protocol. Moreover, the conversion into the cycloSal-pronucleotides and the effect of the orientation of the nucleobase on anti-HIV activity are reported.

Key words

stereoselective synthesis - hydroborations - carbocycles - nucleosides - Mitsunobu reaction

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