The Synthesis of Enantiomerically Pure Pyrazolo[4,3-c]pyridine Carbarzbo C-Nucleoside

Abstract

The synthesis of (-)-3-[(1S,2S,3R,4R)-2,3-dihydroxy-4-(hydroxmethyl) cyclopentan-1-yl]-1H-pyrazolo[4,3-c]pyridme-4,6(5H,7H)-dione 3 was accomplished via enantiomerically pure carbocyclic 5-(β-D-ribofuranosyl)tetrazole 4.

Notes

A mixture of tetrazole 4, Et₃N (1.4 mole equiv.), and dimethyl 3-chloro-2-pentenedioate (1.2 mole equiv.) in THF is stirred at -5°C for 4 h, and concentrated. The residue is dissolved in EtOAc, washed with water, brine, and dried (Na₂SO₄). The concentrated residue is chromatographed on silica gel (eluent petroleum ether/ EtOAc 4:1) to furnish 5 as a light yellow syrup

Light amber solid, m.p. = 214–5°C (from abs. ethanol). [α]d²¹ = -48.6 (c 0.5, H₂0). ¹H NMR (299.94 MHz, D₂O/ TMS): δ 1.51 (m, 1H, H-5′a), 2.29 (m, 2H, H-4′, H-5′b), 3.68 (m, 4H, CH^aH_bOH, H-7_a, H-7_b), 3.91 (m, 1H, H-1′), 3.99 (m, 1H, H-3′), 4.18 (m, 1H, H-2′) ppm. ¹³C NMR (75.43 MHz, Me₂SO-d₆): 30.07 (C-5′), 31.86 (br C-7), 40.57 (br C-l′), 46.89 (C-4′), 63.28 (CH₂OH), 73.18 (C-3′), 75.55 (C-2′), 106.23 (C-3a), 148.60 and 149.33 (br C-3, br C-7a), 162.18 (C-4), 171.33 (br (C-6) ppm. IR (KBr): 3400 (NH, OH), 1704 (CO) cm⁻¹. FABMS m/z 282 (MH⁺).