Glycosidopyrroles. part 4. 1-β-D-ribofuranosyl-pyrroles and indoles as potential antiviral agents

Abstract

The preparation of new 1-β-D-ribofuranosylpyrroles of type 8 and a new method of synthesis of 1-β-D-ribofuranosylindoles of type 10, according to the scheme, is reported. All these new derivatives showed promising chemical and physical analogies with bioactive molecules but did not show any antiviral activity againstHIV1.

3,4-Dihydro-2H-pyrrole-2-carbonitriles: Useful Intermediates in the Synthesis of Fused Pyrroles and 2,2′-Bipyrroles

“…Chemical shifts were referenced to the deuterated solvent (e.g., for CDCl 3 , δ = 7.26 and 77. 16 ppm, for DMSO-d 6 , δ = 2.50 and 39.52 ppm for 1 H and 13 C NMR, respectively) and reported in parts per million (ppm, δ) relative to tetramethylsilane (TMS, δ = 0.00 ppm). 59 Coupling constants (J) are stated in Hz using the splitting abbreviations: s, singlet; d, doublet; t, triplet; quin., quintet; m, multiplet; br, broad.…”

“…The title compound was prepared according to the general procedure described above from cyanopyrroline 1i (162 mg, 0.500 mmol) and Cu(OAc) 2 •H 2 O (300 mg, 1.500 mmol). The crude product was purified by column chromatography (SiO 2 , Cy/EtOAc 10:1) to obtain bipyrrole 6c (14 mg, 0.024 mmol, 10%) as a yellow foam: R f = 0.21 (SiO 2 , Cy/EtOAc 10:1); 1 H NMR, COSY (400 MHz, DMSO-d 6 ) δ (ppm) = 12.08 (d, J = 2.7 Hz, 2H, NH), 7.96 (t, J = 2.0 Hz, 2H, H-2′), 7.90−7.85 (AA′ part of AA′−BB′ system, 4H, H-2″,6″), 7.80 (ddd, J = 8.2, 2.0, 1.0 Hz, 2H, H-4′), 7.60 (ddd, J = 7.8, 2.0, 1.0 Hz, 2H, H-6′), 7.51−7.44 (BB′ part of AA′−BB′ system, 4H, H-3″,5″), 7.38 (pseudo-t, J app ≈ 8 Hz, 2H, H-5′), 7.25 (d, J = 2.7 Hz, 2H, H-4); 13 General Procedure for the Copper(II)-Mediated Homocoupling of Cyanopyrrolines. To a solution of cyanopyrroline 1 (1.00 equiv) in freshly distilled THF (10 mL/mmol 1) were added a solution of LDA (1.20 equiv) in THF/heptane/ethylbenzene at −78 °C under argon athmosphere.…”

“…The title compound was prepared according to the general procedure described above from cyanopyrroline 1b (271 mg, 1.00 mmol), LDA (1.20 mmol), and CuCl 2 (148 mg, 1.10 mmol). Recrystallization from hexanes/CH 2 Cl 2 (8:1) provided compound 7c (88 mg, 0.16 mmol, 33%) as yellow solid: mp 136−138 °C (hexanes/CH 2 Cl 2 ); R f = 0.12 (hexanes/EtOAc 6:1); 1 H NMR, COSY (400 MHz, CDCl 3 ) δ (ppm) = 7.71−7.68 (m, 4H, H-2″,6″), 7.68−7.65 (AA′ part of AA′−BB′ system, 4H, H-3′,5′), 7.49−7.43 (m, 2H, H-4″), 7.43−7.39 (BB′ part of AA′−BB′ system, 4H, H-2′,6′), 7.39−7.30 (m, 4H, H-3″,5″), 4.60 (dd, J = 9.2, 2.8 Hz, 2H, H-3), 3.68 (dd, J = 18.2, 9.2 Hz, 2H, H-4a), 3.32 (dd, J = 18.2, 2.8 Hz, 2H, H-4b); 13 C NMR, HSQC, HMBC (100.6 MHz, CDCl 3 ) δ (ppm) = 181.1 (2C, C-5), 145.8 (2C, C-1′), 133.1 (4C, C-3′,5′), 132.9 (2C, C-4″), 131.5 (2C, C-1″), 129.0 (4C, C-3″,5″), 128.8 (4C, C-2′,6′), 128.2 (4C, C-2″,6″), 118.5 (2C, 4′-CN), 116.6 (2C, 1-CN), 112.5 (2C, C-4′), 87.9 (2C, C-2), 49.0 (2C, C-3), 45.4 (2C, C-4); IR (ATR) ν (cm −1 ) = 3063, 2960, 2926, 2854, 2230, 1609, 1575, 1449, 1348, 1057, 850, 763; ESI-HRMS calcd for [C 36 H 24 N 6 + H] + 541.2141, found 541.2142.…”

“…The title compound was prepared according to the general procedure described above from cyanopyrroline 1g (370 mg, 1.26 mmol), LDA (1.51 mmol), and CuCl 2 (186 mg, 1.38 mmol). Recrystallization from hexanes/EtOAc (5:1) provided compound 7d (228 mg, 0.39 mmol, 62%) as colorless solid: mp 121−122 °C (hexanes/EtOAc); R f = 0.19 (hexanes/EtOAc 2:1); 1 H NMR, COSY (400 MHz, CDCl 3 ) δ (ppm) = 7.75−7.68 (m, 4H, H-2″,6″), 7.22−7.17 (AA′ part of AA′−BB′ system, 4H, H-2′,6′), 7.05−6.98 (m, 4H, H-3″,5″), 6.90−6.86 (BB′ part of AA′−BB′ system, 4H, H-3′,5′), 4.49 (dd, J = 9.2, 2.8 Hz, 2H, H-3), 3.79 (s, 6H, OCH 3 ), 3.54 (dd, J = 18.0, 9.2 Hz, 2H, H-4a), 3.25 (dd, J = 18.0, 2.8 Hz, 2H, H-4b); 13 C NMR, HSQC, HMBC (100.6 MHz, CDCl 3 ) δ (ppm) = 179.5 (2C, C-5), 165.3 (d, 1 J CF = 253.9 Hz, 2C, C-4″), 159.5 (2C, C-4′), 132.8 (2C, C-1′), 130.4 (d, 3 J CF = 8.9 Hz, 4C, C-2″,6″), 128.9 (4C, C-2′,6′), 128.5 (d, 4 J CF = 3. General Procedure for the Synthesis of Bicyclic Structures 8a−p.…”

“…3′,5′,H-4′, H-3″,5″), 4.55 (dd, J = 9.2, 2.6 Hz, 2H, H-3), 3.62 (dd, J = 18.0, 9.2 Hz, 2H, H-4a), 3.33 (dd, J = 18.0, 2.6 Hz, 2H, H-4b);13 C NMR, HSQC, HMBC (100.6 MHz, CDCl 3 ) δ (ppm) = 181. (cm −1 ) = 3060, 3031, 2963, 2926, 2210, 1606, 1594, 1573, 1354, 861, 822, 736; ESI-HRMS calcd for [C 42 H 30 N 4 + Na] + 613.2368, found 613.2370.…”