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Synthesis 2012(5): 723-730  
DOI: 10.1055/s-0031-1289688
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Carbocyclic 4-Deazaformycins

Yan Zhang, Wei Ye, Haisheng Wang, Stewart W. Schneller*
The Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, USA
Fax: +1(334)8440239; e-Mail: schnest@auburn.edu;
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Publication History

Received 13 November 2011
Publication Date:
06 February 2012 (online)

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Abstract

The preparation of carbocyclic 4-deazaformycin and its 5′-homoanalogue from a common vinyl precursor, and its N-1 and N-2 methyl derivatives is reported. The syntheses began with a highly stereoselective SN2 reaction between lithio 4-picolines and a protected 2,3-dihydroxy-4-vinylcyclopentyl triflate. The requisite fused pyrazole ring was created by an intramolecular diazonium reaction that was followed by vinyl transformation into the hydroxymethyl and the hydroxyethyl groups. The N-methyl derivatives arose by standard methylation conditions and the resultant N-Me regiochemistry was assigned by homo- and heteronuclear NMR spectroscopy.

Key words

C-nucleosides - carbocyclic nucleosides - pyrazolo[3,4-c]pyridines

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10

Crystallographic data (Figure  [³] ) for 25, which was a minor product in the ammonolysis of 12 have been deposited with Cambridge Crystallographic Data Centre (e mail: ccdc@code.cam.ac.uk) and allocated the deposition number CCDC 851387.

Figure 3 Hydrolyis side-product from 12