5′-Noraristeromycin C-Nucleosides Based on Imidazo[1,2-a]pyrazine

Abstract

The preparation of two C-5′-nor-3-deazaaristeromycin dia­stereomeric analogues possessing a bridgehead nitrogen is described from (3aR,4R,6S,6aS)-2,2-dimethyl-6-vinyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol that served as the cyclopentyl unit of the target carbocyclic nucleosides and as the scaffold upon which the compounds were built. The process evolved via a de novo approach for constructing the requisite fused imidazo unit between the aforementioned cyclopentyl ring and a readily available 2,3-dichloropyrazine. The syntheses were accomplished in 11 and 8 steps depending on the diastereomer sought.

Key words

formycin - carbocyclic nucleosides - bridgehead nitrogen nucleoside base

• References


See, for example:
• 1a Goodman HM, Abelson J, Landy A, Brenner S, Smith JD. Nature 1968; 217: 1019
• 1b Jackson KE, Pogula PK, Patterson SE. Heterocycl. Commun. 2013; 19: 375
• 2a Stambasky J, Hocek M, Kocovsky P. Chem. Rev. 2009; 109: 6729
• 2b Jenkins GN, Turner NJ. Chem. Soc. Rev. 1995; 24: 169
• 3a Bzowska A In Modified Nucleosides . Herdewijn P. Wiley-VCH; Weinheim: 2008: 473
• 3b Simons C. Nucleoside Mimetics: Their Structure and Biological Properties. Gordon and Breach; Amsterdam: 2000: 117
• 4a Simons C. Nucleoside Mimetics: Their Structure and Biological Properties. Gordon and Breach; Amsterdam: 2000: 137
• 4b Crimmins MT. Tetrahedron 1998; 54: 9229
• 5a Mieczkowski A, Agrofoglio LA In Modified Nucleosides . Herdewijn P. Wiley-VCH; Weinheim: 2008: 393
• 5b Tosh DK, Kim HO, Pal S, Lee JA, Jeong LS In Modified Nucleosides . Herdewijn P. Wiley-VCH; Weinheim: 2008: 525
• 6 For a leading reference, see: Zhang Y, Ye W, Wang H, Schneller SW. Synthesis 2012; 44: 723
• 7 For a leading reference, see: Chong L, Chen Q, Yang M, Schneller SW. Bioorg. Med. Chem. 2013; 21: 359
• 8 Siddiqi SM, Chen X, Rao J, Schneller SW, Ikeda S, Snoeck R, Andrei G, Balzarini J, De Clercq E. J. Med. Chem. 1995; 38: 1035
• 9 MacCoss M, Meurer LC, Hoogsteen K, Springer JP, Koo G, Peterson LB, Tolman RL. J. Heterocycl. Chem. 1993; 30: 1213
• 10 Li W, Ye W, Schneller SW. Tetrahedron 2012; 68: 65
• 11 Smith AB. III, Han Q, Breslin PA. S, Beauchamp GK. Org. Lett. 2005; 7: 5075
• 12 Saïah M, Bessodes M, Antonakis K. Tetrahedron Lett. 1992; 33: 4317
• 13 For the ¹H NMR for the enantiomer of 11, see: Marschner C, Penn G, Griengl H. Tetrahedron 1993; 49: 5067
• 14 Murray RW, Singh M. Org. Synth. 1997; 74: 91
• 15 Crystallographic data for 16 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1005186. Copies of the data can be obtained, free of charge, on request to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: [phone] or e-mail: [e-mail].