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Synthesis 2005(6): 925-932  
DOI: 10.1055/s-2005-861831
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Purinyl homo-Carbonucleoside Derivatives of 2-Benzylcyclopenta[c]pyrazol

Marcos D. Garcíaa, Olga Caamaño*a, Franco Fernándeza, Carmen Lópeza, Erick De Clercqb
a Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax: +34(981)594912; e-Mail: qoolga@usc.es;
b Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
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Publication History

Received 16 December 2004
Publication Date:
14 February 2005 (online)

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Abstract

The first members of a new class of carbocyclic nucleoside analogs were synthesized via key intermediate (±)-(cis)-2-bencylcyclopenta[c]pyrazole-4,6-dimethanol, which was obtained from the easily prepared starting compound (±)-(exo,exo)-5,6-isopropylidenedioxy-4,5,6,7-tetrahydro-4,7-methano-2H-indazole by a reaction sequence in which the key step was a one-pot oxidative cleavage of glycol 9 and reduction of the resulting dialdehyde with NaBH4. Purine moieties were coupled by nucleophilic displacement following mesylation of the latter. The new compounds 15 and 17 are active against cytomagalovirus and varicella-zoster virus at subcytotoxical concentrations.

Key words

methanoindazoles - purinyl carbonucleosides - antiviral activity - benzylcyclopenta[c]pyrazol - glycol cleavage

13

Hydrazine hydrate (3.6 mL, 19.72 mmol) was added under argon to a well-stirred solution of freshly prepared (exo,exo)-3-(hydroxymethylene)-5,6-isopropylidenedioxy)bicyclo-[2.2.1]heptan-2-one [20] (3.46 g, 16.48 mmol) in anhyd toluene (150 mL) containing a small amount of TsOH as catalyst, and the mixture was refluxed for 12 h in a Dean-Stark apparatus. The solvent was evaporated under reduced pressure and the red solid residue (3.41 g) was purified by chromatography on a silica gel column using hexane-EtOAc (1:1) as eluent. Compound 6 was isolated from appropriate fractions as a white solid (2.28 g, 67%), with mp and spectroscopic features identical to those previously described. [11]

17

The crystallographic data of 10 and 18 have been deposited at the Cambridge Crystallographic Data Centre as Supplementary Publications CCDC 240518 and CCDC 240519 respectively. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK.