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Synlett 2009(18): 2927-2930  
DOI: 10.1055/s-0029-1218002
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

The Synthesis of 6-Deazaformycin A

Tony Tite, Nikolaos Lougiakis, Panagiotis Marakos, Nicole Pouli*
Department of Pharmacy, Division of Pharmaceutical Chemistry, University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Fax: +30(210)7274747; e-Mail: pouli@pharm.uoa.gr;
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Publication History

Received 21 July 2009
Publication Date:
02 October 2009 (online)

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Abstract

The synthesis of the new C-nucleoside 6-deazaformycin A was achieved through the condensation of a suitably substituted lithiated 2-picoline with 2,3,5-tri-O-benzyl-d-ribonolactone, borohydride reduction of the resulting hemiacetals, followed by intramolecular Mitsunobu cyclization of the carbinols, manipulation of the protecting groups, and subsequent ring closure to result in the formation of 7-amino-3-(β-d-ribofuranosyl)pyrazolo[4,3-b]pyridine.

Key words

C-nucleosides - heterocycles - formycin A - pyrazolo[4,3-b]pyridine

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Data for tert -Butyl- N -[3-amino-2-(2,3,5-tri- O -benzyl-β- d -ribofuranosylmethyl)pyridin-4-yl]carbamate (14)
Oil. ¹H NMR (400 MHz, CDCl3): δ = 1.55 (s, 9 H, t-Bu), 3.00 (dd, 1 H, 2-CH2, J = 7.33, 13.69 Hz), 3.10 (dd, 1 H, 2-CH2, J = 3.91, 13.69 Hz), 3.42 (dd, 1 H, H-5′, J5 ′ ,4 ′ = 4.40 Hz, J 5 ′ ,5 ′ = 10.27 Hz), 3.45-3.56 (br s, 2 H, D2O exchange, NH2), 3.56 (dd, 1 H, H-5′, J 5 ′ ,4 ′ = 2.94 Hz, J 5 ′ ,5 ′ = 10.27 Hz), 3.72 (t, 1 H, H-3′, J = 5.87 Hz), 3.92 (t, 1 H, H-2′, J = 4.40 Hz), 4.16-4.21 (m, 1 H, H-4′), 4.38-4.68 (m, 7 H, H-1′, 6 × CH2Ph), 6.91 (s, 1 H, D2O exchange, NHBoc), 7.23-7.41 (m, 15 H, 3 × C6H5), 7.63 (d, 1 H, H-5, J 5,6 = 5.38 Hz), 8.05 (d, 1 H, H-6, J 6,5 = 5.38 Hz). ¹³C NMR (50 MHz CDCl3): δ = 28.40 [(CH3)3CCONH], 39.34 (CH2), 69.64 (C-5′), 72.08, 73.41 (CH2Ph), 77.16 (C-3′), 79.61 (C-2′), 80.52 (C-4′), 81.29 [(CH3)3 CCONH], 82.60 (C-1′), 112.73 (C-5), 127.80, 127.88, 128.14, 128.45, 128.54 (tertiary benzylic CH), 130.80 (C-3), 136.62 (C-4), 137.93, 138.09, 138.16 (quaternary benzylic C), 142.27 (C-6), 148.53 (C-2),152.58 (CO).

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Data for 7-Amino-(3-β- d -ribofuranosyl)pyrazolo[4,3- b ]pyridine (30)
Pale yellow foam. ¹H NMR (400 MHz, CD3OD): δ = 3.82 (dd, 1 H, H-5′, J 5 ′ ,4 ′ = 12.13 Hz, J 4 ′ ,5 ′′ = 2.35 Hz), 3.94 (dd, 1 H, H-5′, J 5 ′ ,4 ′ = 12.13 Hz, J 4 ′ ,5 ′′ = 2.74 Hz), 4.15-4.19 (m, 1 H, H-4′), 4.28 (dd, 1 H, H-3′, J 3 ′ ,2 ′ = 5.08 Hz, J 3 ′ ,4 ′′ = 3.52 Hz), 4.48 (dd, 1 H, H-2′, J 2 ′ ,3 ′ = 5.08 Hz, J 2 ′ ,1 ′′ = 7.04 Hz), 5.22 (d, 1 H, H-1′, J 1 ′ ,2 ′′ = 7.04 Hz), 6.65 (d, 1 H, H-6, J 6,5 = 5.86 Hz), 8.07 (d, 1 H, H-5, J 5,6 = 5.86 Hz). ¹³C NMR (50 MHz, CD3OD): δ = 63.28 (C-5′), 73.74 (C-3′), 77.50 (C-2′), 80.80 (C-1′), 87.16 (C-4′), 102.89 (C-6), 129.15 (C-7α), 132.90 (C-3α), 143.15 (C-5), 143.22 (C-3), 146.97 (C-7). Anal. Calcd for C11H14N4O4: C, 49.62; H, 5.30; N, 21.04. Found: C, 49.81; H, 5.22; N, 20.87.

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Data for 4-[(β- d -Ribofuranosyl)methyl]-3 H -[1,2,3]triazolo[4,5- c ]pyridine (31)
Oil. ¹H NMR (400 MHz, CDCl3): δ = 3.52-3.63 (m, 2 H, CH2, H-5′), 3.65-3.74 (m, 2 H, CH2, H-5′), 3.80-3.86 (m, 1 H, H-4′), 4.02 (t, 1 H, H-3′), 4.17 (t, 1 H, H-2′), 4.30-4.37 (m, 1 H, H-1′), 7.81 (d, 1 H, H-7, J 7,6 = 6.26 Hz), 8.30 (d,
1 H, H-6, J 6,7 = 6.26 Hz). ¹³C NMR (50 MHz CDCl3): δ = 38.49 (CH2), 62.64 (C-5′), 72.21 (C-3′), 76.64 (C-2′), 83.41 (C-4′), 85.95 (C-1′), 109.07 (C-7), 139.48 (C-6), 142.29 (C-3α), 144.67 (C-7α), 153.13 (C-4). Anal. Calcd for C11H14N4O4: C, 49.62; H, 5.30; N, 21.04. Found: C, 49.55; H, 5.09; N, 21.18.