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Synthesis 2006(12): 2005-2012  
DOI: 10.1055/s-2006-942400
PAPER
© Georg Thieme Verlag Stuttgart · New York

Fluorinated Pyrrolo[2,3-d]pyrimidine Nucleosides: 7- Fluoro-7-deazapurine 2′-Deoxyribofuranosides and 2′-Deoxy-2′-fluoroarabinofuranosyl Derivatives

Frank Seela*a,b, Kuiying Xua,b, Padmaja Chittepua,b
a Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück, Barbarastr. 7, 49069 Osnabrück, Germany
b Center for Nanotechnology (CeNTech), Gievenbecker Weg 11, 48149 Münster, Germany
Fax: +49(541)9692370; e-Mail: Frank.Seela@uni-osnabrueck.de;
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Publikationsverlauf

Received 19 January 2006
Publikationsdatum:
17. Mai 2006 (online)

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Abstract

The syntheses of 7-deaza-7-fluoro-2′-deoxyadenosine (1a), 7-deaza-7-fluoro- 2′-deoxyinosine (3a) and 7-deaza-7-fluoro-2′-deoxyguanosine (3c) as well as of the 2′-deoxy-2′-fluoroarabinofuranosyl derivatives 1b, 3b are described. Starting materials were 6-chloro-7-fluoro-7-deazapurine (4-chloro-5-fluoropyrrolo[2,3-d]pyrimidine, 4b) and 2-pivaloylamino-6-chloro-7-fluoro-7-deaza­purine (2-pivaloylamino-4-chloro-5-fluoropyrrolo[2,3-d]pyrimidine, 6). Nucleobase anion glycosylation of 4b or 6 with the halogenoses 7 or 9 furnished the protected β-d-nucleosides 8, 10 and 11, which were converted to compounds 1a, 1b by ammonolysis and to 2a-c by sodium methoxide treatment. The 2′-deoxy­inosine derivatives 3a, 3b and the guanosine analogue 3c were obtained from 2a-c. Conformational analysis of the nucleosides 1a, 1b was performed in solution and in the solid state. Single-crystal X-ray analyses showed that the sugar moiety of 1a exhibits the S-conformation (P = 164.8°, τ = 40.1°). In solution the 2′-fluoro substituents shift the sugar conformation slightly towards N.

Key words

fluorine - glycosylations - pyrrolo[2,3-d]pyrimidines - nucleosides - sugar conformation