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PMC:7291971 / 34244-85021 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T245 0-14 Sentence denotes 4.1 Chemistry
T246 16-41 Sentence denotes 4.1.1 General procedures
T247 42-156 Sentence denotes All dry solvents and reagents were purchased from commercial suppliers and were used without further purification.
T248 157-197 Sentence denotes DIEA was distilled over calcium hydride.
T249 198-280 Sentence denotes Thin-layer chromatography (TLC) analyses were carried out on silica plate 60 F254.
T250 281-400 Sentence denotes Purifications by column chromatography were performed using Biotage Isolera 1 system with FlashPure cartridges (Buchi).
T251 401-484 Sentence denotes NMR experiments were recorded on Bruker 400, 500 or 600 MHz spectrometers at 20 °C.
T252 485-599 Sentence denotes HRMS analyses were obtained with electrospray ionization (ESI) in positive mode on a Q-TOF Micromass spectrometer.
T253 600-788 Sentence denotes Analytical HPLC was performed on a UHPLC Thermoscientific Ultimate 3000 system equipped with a LPG-3400RS pump, a DAD 3000 detector and an WPS-3000TBRS Autosampler, Column Oven TCC-3000SD.
T254 789-907 Sentence denotes Dinucleosides 1–16 were analyzed by RP-HPLC on a Column Nucleodur C18 ec 100-3, 4.6 × 75 mm (Macherey Nagel) at 30 °C.
T255 908-953 Sentence denotes The following HPLC solvent systems were used:
T256 954-1030 Sentence denotes 1% CH3CN in 12.5 mM TEAAc (buffer A), 80% CH3CN in 12.5 mM TEEAc (buffer B).
T257 1031-1054 Sentence denotes Flow rate was 1 mL/min.
T258 1055-1092 Sentence denotes UV detection was performed at 260 nm.
T259 1093-1185 Sentence denotes Lyophilized compounds 1–16 were stored at −20 °C for several months without any degradation.
T260 1187-1259 Sentence denotes 4.1.2 General method A for the synthesis of compounds 18, 26, 27 and 29
T261 1260-1340 Sentence denotes To a solution of 5′-amino-2′,3′-isopropylidene adenosine in anhydrous DMF (conc.
T262 1341-1442 Sentence denotes 0.2 M) was added Et3N (2.00 eq) and the corresponding nitrobenzenesufonyl chloride (1.50 eq) at 0 °C.
T263 1443-1554 Sentence denotes The reaction mixture was stirred for 4 h at room temperature under argon then was diluted with AcOEt and brine.
T264 1555-1704 Sentence denotes The aqueous layer was extracted with AcOEt and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under vacuum.
T265 1705-1798 Sentence denotes The precipitate was washed with Et2O and DCM to give the desired compound as a colored solid.
T266 1800-1942 Sentence denotes 4.1.3 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-4-nitrobenzene-1-sulfonamide (18)
T267 1943-2119 Sentence denotes Following method A with 5′-amino-2′,3′-isopropylidene adenosine (2.21 g, 7.22 mmol, 1.00 eq) and 4-nitrobenzenesufonyl chloride, 18 (2.64 g, 74%) was obtained as a beige solid.
T268 2120-2144 Sentence denotes Rf 0.50 (8:92 MeOH/DCM).
T269 2145-2461 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.55 (t, J = 5.8 Hz, 1H), 8.33–8.27 (m, 2H), 8.26 (s, 1H), 8.13 (s, 1H), 7.96–7.88 (m, 2H), 7.37 (br. s, 2H), 6.09 (d, J = 2.8 Hz, 1H), 5.32 (dd, J = 6.3 Hz, 2.9 Hz, 1H), 4.89 (dd, J = 6.3 Hz, 3.0 Hz, 1H), 4.16 (td, J = 5.9 Hz, 3.0 Hz, 1H), 3.24–3.10 (m, 2H), 1.50 (s, 3H), 1.27 (s, 3H).
T270 2462-2603 Sentence denotes 13C NMR (600 MHz, DMSO‑d 6) δ 156.3, 152.7, 149.5, 148.4, 146.0, 140.2, 128.0, 124.5, 119.3, 113.6, 89.4, 84.4, 83.0, 81.6, 44.6, 27.0, 25.2.
T271 2604-2650 Sentence denotes HRMS (ESI+): m/z calcd for C19H22N7O7S [M+H]+:
T272 2651-2676 Sentence denotes 492.1301, Found 492.1311.
T273 2678-2742 Sentence denotes 4.1.4 General method B for the synthesis of compounds 19, 30-33
T274 2743-2795 Sentence denotes To a solution of 18 or 26–29 in anhydrous DMF (conc.
T275 2796-2874 Sentence denotes 0.13 M) was successively added 17 (1.10 eq), KI (0.30 eq) and K2CO3 (3.00 eq).
T276 2875-2965 Sentence denotes After stirring for 24 h at 50 °C under argon, the reaction was diluted in AcOEt and water.
T277 2966-3115 Sentence denotes The aqueous layer was extracted with AcOEt and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under vacuum.
T278 3116-3265 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–8% MeOH in DCM) to give the desired compound as colored solid.
T279 3267-3546 Sentence denotes 4.1.5 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)-4-nitrobenzene-1-sulfonamide (19)
T280 3547-3658 Sentence denotes Following method B using 18 (290 mg, 0.59 mmol, 1.00 eq), 19 (450 mg, 74%) was obtained as a pale yellow solid.
T281 3659-3684 Sentence denotes Rf 0.60 (10:90 MeOH/DCM).
T282 3685-4205 Sentence denotes 1H NMR (600 MHz, CDCl3) δ 8.30 (2s, 2H), 8.14 (s, 1H), 8.03–7.98 (m, 2H), 7.74 (s, 1H), 7.70–7.66 (m, 2H), 6.11–5.93 (m, 5H), 5.89 (d, J = 1.9 Hz, 1H), 5.35 (dd, J = 6.4 Hz, J = 1.9 Hz, 1H), 5.04 (dd, J = 6.4 Hz, J = 3.8 Hz, 1H), 4.51 (dd, J = 6.1 Hz, J = 4.6 Hz, 1H), 4.43 (dt, J = 8.5 Hz, J = 4.2 Hz, 1H), 4.22 (dd, J = 4.7 Hz, J = 3.2 Hz, 1H), 4.05 (dt, J = 5.9 Hz, J = 3.0 Hz, 1H), 3.99 (dd, J = 11.5 Hz, J = 3.5 Hz, 1H), 3.85–3.41 (m, 7H), 1.57 (s, 3H), 1.35 (s, 3H), 0.92 (s, 9H), 0.91 (s, 9H), 0.14–0.04 (m, 12H).
T283 4206-4469 Sentence denotes 13C NMR (150 MHz, CDCl3) δ 155.8, 155.5, 153.2, 153.0, 149.7, 149.5, 148.9, 145.4, 140.2, 139.5, 128.4, 123.8, 120.5, 120.2, 114.7, 90.7, 87.3, 85.0, 84.5, 84.2, 82.8, 82.6, 69.7, 69.6, 61.5, 50.7, 47.7, 27.3, 26.2, 25.9, 25.4, 18.6, 18.2, −4.4, −4.7, −5.2, −5.3.
T284 4470-4521 Sentence denotes HRMS (ESI+): m/z calcd for C43H65N12O11SSi2 [M+H]+:
T285 4522-4539 Sentence denotes 1013.4155, found:
T286 4540-4550 Sentence denotes 1013.4155.
T287 4552-4796 Sentence denotes 4.1.6 9-[(2R,5R)-3-[2-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}amino)ethoxy]-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-2-yl]-9H-purin-6-amine (20)
T288 4797-4958 Sentence denotes To a solution of 19 (210 mg, 0.20 mmol, 1.00 eq) in anhydrous DMF (10 mL) was added K2CO3 (85 mg, 0.61 mmol, 3.00 eq) and thiophenol (11 μL, 1.14 mmol, 5.70 eq).
T289 4959-5115 Sentence denotes After stirring for 2 h at room temperature under argon, the reaction mixture was diluted with DCM (20 mL) and washed with 1 M aqueous NaOH solution (10 mL).
T290 5116-5275 Sentence denotes The aqueous layer was extracted with DCM (3 × 20 mL) and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under vacuum.
T291 5276-5436 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–15% MeOH in DCM) as the eluent to give 20 (129 mg, 76%) as a white solid.
T292 5437-5461 Sentence denotes Rf 0.31 (8:92 MeOH/DCM).
T293 5462-5917 Sentence denotes 1H NMR (500 MHz, CDCl3) δ 8.32 (s, 1H), 8.31 (s, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 6.17–6.06 (m, 5H), 6.03 (d, J = 2.9 Hz, 1H), 5.39 (dd, J = 6.5 Hz, J = 3.0 Hz, 1H), 4.99–4.92 (m, 1H), 4.51–4.45 (m, 1H), 4.33–4.25 (m, 2H), 4.08 (dt, J = 5.6 Hz, J = 3.2 Hz, 1H), 3.98 (dd, J = 11.5 Hz, J = 3.6 Hz, 1H), 3.75 (dd, J = 11.6 Hz, J = 2.8 Hz, 1H), 3.71–3.63 (m, 2H), 2.95–2.69 (m, 4H), 1.61 (s, 3H), 1.37 (s, 3H), 0.92 (s, 9H), 0.88 (s, 9H), 0.13–0.04 (m, 12H).
T294 5918-6148 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 155.8, 155.7, 153.3, 153.1, 149.7, 149.6, 139.8, 139.4, 120.5, 120.3, 114.8, 90.7, 87.2, 85.8, 85.1, 83.9, 82.6, 82.4, 70.3, 70.13, 62.0, 51.5, 49.5, 27.4, 26.2, 25.8, 18.6, 18.2, −4.5, −4.8, −5.2, −5.3.
T295 6149-6198 Sentence denotes HRMS (ESI+): m/z calcd for C37H62N11O7Si2 [M+H]+:
T296 6199-6215 Sentence denotes 828.4372, found:
T297 6216-6225 Sentence denotes 828.4371.
T298 6227-6301 Sentence denotes 4.1.7 General method C for the synthesis of compounds 1, 3, 5–7, 9, 10-16
T299 6302-6390 Sentence denotes The synthesis intermediate was treated at room temperature with TFA in water (8/2, conc.
T300 6391-6399 Sentence denotes 0.14 M).
T301 6400-6558 Sentence denotes After stirring for 3–6 h until completion of reaction (TLC DCM/MeOH), solvents were removed and the residue was coevaporated three times with 7 M NH3 in MeOH.
T302 6559-6737 Sentence denotes The residue was purified by flash column chromatography on a reversed-phase silica gel column C18 (4 g, 40 μm) with a linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7.
T303 6738-6879 Sentence denotes The fractions containing the pure compound were pooled, concentrated and lyophilized with water/dioxane to give desired compound as a powder.
T304 6881-7047 Sentence denotes 4.1.8 (2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)amino]methyl}oxolane-3,4-diol (1)
T305 7048-7294 Sentence denotes Following method C with 20 (117 mg, 0.14 mmol, 1.00 eq) and a 0–25% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 1 (60 mg, 76%) was obtained as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T306 7295-7678 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.38 (s, 1H), 8.34 (s, 1H), 8.15 (s, 1H), 8.14 (s, 1H), 7.36 (br.s, 2H), 7.29 (br. s, 2H), 5.97 (d, J = 6.4 Hz, 1H), 5.85 (d, J = 5.9 Hz, 1H), 5.58–4.98 (m, 4H), 4.70–4.63 (m, 1H), 4.52 (dd, J = 6.4 Hz, J = 4.7 Hz, 1H), 4.33 (dd, J = 4.7 Hz, J = 2.6 Hz, 1H), 4.12 (dd, J = 5.2 Hz, J = 3.8 Hz, 1H), 4.02–3.93 (m, 2H), 3.70–3.48 (m, 4H), 2.86–2.58 (m, 4H).
T307 7679-7849 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 156.2, 156.1, 152.6, 152.5, 149.4, 149.0, 140.1, 139.9, 119.4, 119.3, 87.6, 86.3 (2C), 83.7, 81.5, 72.8, 71.5, 69.5, 69.1, 61.7, 51.2, 49.0.
T308 7850-7896 Sentence denotes HRMS (ESI+): m/z calcd for C22H30N11O7 [M+H]+:
T309 7897-7914 Sentence denotes 560.23242, found:
T310 7915-7925 Sentence denotes 560.23188.
T311 7927-8238 Sentence denotes 4.1.9 Methyl (2S)-4-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)amino)-2-{bis[(tert-butoxy)carbonyl]amino}butanoate (22)
T312 8239-8431 Sentence denotes To a solution of 20 (250 mg, 0.30 mmol, 1.00 eq) in anhydrous DCM (9 mL) was added aldehyde 21 (120 mg, 0.36 mmol, 1.20 eq) in anhydrous DCM (9 mL) and acetic acid (20 μL, 0.36 mmol, 1.20 eq).
T313 8432-8557 Sentence denotes After stirring for 20 min at room temperature under argon, sodium triacetoxyborohydride (96 mg, 0.45 mmol, 1.5 eq) was added.
T314 8558-8683 Sentence denotes After stirring for 2.5 h, the reaction mixture was diluted with DCM (30 mL) and washed with saturated aqueous NaHCO3 (30 mL).
T315 8684-8843 Sentence denotes The aqueous layer was extracted with DCM (3 × 30 mL) and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under vacuum.
T316 8844-8989 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–8% MeOH in DCM) to give 22 (321 mg, 93%) as a white solid.
T317 8990-9014 Sentence denotes Rf 0.71 (MeOH/DCM 5:95).
T318 9015-9562 Sentence denotes 1H NMR (600 MHz, CDCl3) δ 8.33 (s, 1H), 8.30 (s, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 6.09 (d, J = 3.3 Hz, 1H), 6.01 (d, J = 2.4 Hz, 1H), 5.97 (m, 4H), 5.42 (dd, J = 6.5 Hz, J = 2.4 Hz, 1H), 4.93–4.86 (m, 2H), 4.54–4.49 (m, 1H), 4.33 (td, J = 6.8 Hz, J = 3.3 Hz, 1H), 4.29–4.24 (m, 1H), 4.08 (dt, J = 6.2 Hz, J = 3.2 Hz, 1H), 3.99 (dd, J = 11.5 Hz, J = 3.7 Hz, 1H), 3.78–3.63 (m, 6H), 2.84–2.74 (m, 3H), 2.71–2.51 (m, 3H), 2.33–2.23 (m, 1H), 1.91–1.82 (m, 1H), 1.58 (s, 3H), 1.46 (s, 18H), 1.36 (s, 3H), 0.91 (s, 9H), 0.90 (s, 9H), 0.10–0.05 (m, 12H).
T319 9563-9849 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 171.6, 155.8, 155.7, 153.3, 153.2, 152.3, 149.7, 149.5, 140.1, 139.8, 120.5, 120.4, 114.5, 91.1, 87.4, 85.45, 84.8, 84.1, 83.3, 83.3, 82.5, 69.9, 69.1, 61.9, 56.3, 56.3, 53.7, 52.4, 52.1, 28.1, 28.1, 27.3, 26.2, 26.0, 25.6, 18.7, 18.3, −4.3, −4.6, −5.2, −5.2.
T320 9850-9900 Sentence denotes HRMS (ESI+): m/z calcd for C52H87N12O13Si2 [M+H]+:
T321 9901-9918 Sentence denotes 1143.6049, found:
T322 9919-9929 Sentence denotes 1143.6043.
T323 9931-10134 Sentence denotes 4.1.10 (2S)-4-({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)amino)-2-azaniumylbutanoate (2)
T324 10135-10243 Sentence denotes Compound 22 (86 mg, 75.3 μmol, 1.00 eq) was treated at room temperature with TFA (830 μL) in water (210 μL).
T325 10244-10303 Sentence denotes After stirring for 3 h, solvents were removed under vacuum.
T326 10304-10395 Sentence denotes The residue was dissolved in water (0.5 mL) and 2 M aqueous LiOH solution (4 mL) was added.
T327 10396-10496 Sentence denotes After stirring at 0 °C for 30 min, pH ≈ 3 or 4 was adjusted by addition of 1 M aqueous HCl solution.
T328 10497-10722 Sentence denotes The solvent was removed under vacuum and the residue was purified by flash column chromatography on a reversed-phase silica gel column C18 (4 g, 40 μm) with a 0–15% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7.
T329 10723-10914 Sentence denotes The fractions containing the pure compound were pooled, concentrated and lyophilized with water to give 2 (16 mg, 32%) as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T330 10915-11349 Sentence denotes 1H NMR (600 MHz, D2O) δ 8.11 (s, 1H), 8.05 (s, 1H), 7.98 (s, 1H), 7.86 (s, 1H), 5.89 (d, J = 2.5 Hz, 1H), 5.77 (d, J = 3.3 Hz, 1H), 4.51–4.47 (m, 2H), 4.36 (dd, J = 5.1 Hz, J = 3.4 Hz, 1H), 4.34–4.29 (m, 1H), 4.14–4.08 (m, 2H), 3.97 (td, J = 10.6 Hz, J = 2.4 Hz, 1H), 3.89–3.80 (m, 3H), 3.71 (dd, J = 13.0, J = 3.4 Hz, 1H), 3.15–3.04 (m, 2H), 3.03–2.81 (m, 2H), 2.76 (d, J = 14.2 Hz, 1H), 2.58 (d, J = 13.8 Hz, 1H), 2.14–1.99 (m, 2H).
T331 11350-11538 Sentence denotes 13C NMR (150 MHz, D2O) δ 174.5, 154.9 (2C) 152.5, 152.2, 147.7, 147.5, 139.3, 138.5, 118.5, 118.2, 89.0, 86.8, 84.8, 81.7, 80.0, 73.9, 71.1, 68.9, 67.7, 60.3, 56.2, 55.3, 53.8, 52.5, 26.1.
T332 11539-11585 Sentence denotes HRMS (ESI+): m/z calcd for C26H37N12O9 [M+H]+:
T333 11586-11602 Sentence denotes 661.2806, found:
T334 11603-11612 Sentence denotes 661.2811.
T335 11614-11820 Sentence denotes 4.1.11 Methyl (2S)-2-amino-4-({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)amino)butanoate (3)
T336 11821-12067 Sentence denotes Following method C with 22 (140 mg, 0.12 mmol, 1.00 eq) and a 0–30% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 3 (28 mg, 35%) was obtained as a white powder with 98% purity determined by HPLC analysis at 260 nm.
T337 12068-12603 Sentence denotes 1H NMR (600 MHz, D2O) δ 8.08 (s, 1H), 8.05 (s, 1H), 7.98 (s, 1H), 7.84 (s, 1H), 5.89 (d, J = 2.5 Hz, 1H), 5.75 (d, J = 3.3 Hz, 1H), 4.55–4.50 (m, 1H), 4.47 (dd, J = 5.1 Hz, J = 2.3 Hz, 1H), 4.38 (dd, J = 5.0 Hz, J = 3.2 Hz, 1H), 4.36–4.30 (m, 1H), 4.26 (dd, J = 10.5 Hz, J = 2.8 Hz, 1H), 4.13 (dd, J = 7.9 Hz, J = 5.1 Hz, 1H), 4.07 (dt, J = 6.2 Hz, J = 3.1 Hz, 1H), 4.05–3.86 (m, 2H), 3.84 (s, 3H), 3.82–3.64 (m, 2H), 3.22–3.01 (m, 3H), 2.88 (dt, J = 13.7, J = 3.9, 1H), 2.78 (d, J = 13.9 Hz, 1H), 2.66–2.58 (m, 1H), 2.19–2.02 (m, 2H).
T338 12604-12793 Sentence denotes 13C NMR (150 MHz, D2O) δ 170.6, 154.9 (2C), 152.5, 152.2, 147.7, 147.4, 139.1, 138.3, 118.5, 118.1, 89.1, 86.8, 84.6, 81.8, 79.6, 73.9, 70.9, 69.1, 60.2, 54.8, 54.1, 53.5, 53.3, 52.3, 25.0.
T339 12794-12840 Sentence denotes HRMS (ESI+): m/z calcd for C27H39N12O9 [M+H]+:
T340 12841-12857 Sentence denotes 675.2957, found:
T341 12858-12867 Sentence denotes 675.2944.
T342 12869-13069 Sentence denotes 4.1.12 (2S)-2-amino-4-({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)amino)butanamide (4)
T343 13070-13220 Sentence denotes Compound 22 (116 mg, 0.10 mmol, 1.00 eq) was treated at room temperature with TFA (1.44 mL) in water (360 μL) and stirred for 3 h at room temperature.
T344 13221-13304 Sentence denotes The solvents were removed and the residue was treated with 7 M NH3 in MeOH (10 mL).
T345 13305-13549 Sentence denotes After stirring for 24 h at 30 °C, solvents were removed and the residue was purified by flash column chromatography on a reversed-phase silica gel column C18 (4 g, 40 μm) with a 0–15% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7.
T346 13550-13741 Sentence denotes The fractions containing the pure compound were pooled, concentrated and lyophilized with water to give 4 (23 mg, 38%) as a white powder with 98% purity determined by HPLC analysis at 260 nm.
T347 13742-14204 Sentence denotes 1H NMR (600 MHz, D2O) δ 8.12 (s, 1H), 8.08 (s, 1H), 7.99 (s, 1H), 7.90 (s, 1H), 5.90 (d, J = 2.7 Hz, 1H), 5.79 (d, J = 3.5 Hz, 1H), 4.53 (dd, J = 5.2 Hz, J = 2.7 Hz, 1H), 4.52–4.48 (m, 1H), 4.38 (dd, J = 5.0 Hz, J = 3.6 Hz, 1H), 4.35–4.28 (m, 1H), 4.18–4.07 (m, 3H), 3.98 (td, J = 10.7 Hz, J = 2.6 Hz, 1H), 3.88–3.80 (m, 2H), 3.72 (dd, J = 12.9 Hz, J = 3.5 Hz, 1H), 3.16–2.98 (m, 3H), 2.88–2.76 (m, 2H), 2.62 (dt, J = 14.0 Hz, J = 2.7 Hz, 1H), 2.17–1.98 (m, 2H).
T348 14205-14393 Sentence denotes 13C NMR (150 MHz, D2O) δ 173.0, 155.0 (2C) 152.5, 152.3, 147.8, 147.6, 139.4, 138.7, 118.6, 118.3, 88.9, 86.8, 84.9, 81.8, 79.8, 73.8, 71.1, 69.0, 67.6, 60.4, 55.3, 53.9, 52.6, 52.4, 27.0.
T349 14394-14440 Sentence denotes HRMS (ESI+): m/z calcd for C26H38N13O8 [M+H]+:
T350 14441-14457 Sentence denotes 660.2961, found:
T351 14458-14467 Sentence denotes 660.2966.
T352 14469-14538 Sentence denotes 4.1.13 General method D for the synthesis of compounds 23, 24 and 25
T353 14539-14582 Sentence denotes To a solution of 20 in anhydrous NMP (conc.
T354 14583-14664 Sentence denotes 0.03 M) was added the corresponding bromide reagent (3.00 eq) and DIEA (3.00 eq).
T355 14665-14770 Sentence denotes After stirring for 4 h at 110 °C under microwaves, the reaction mixture was diluted with AcOEt and brine.
T356 14771-14920 Sentence denotes The aqueous layer was extracted with AcOEt and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under vacuum.
T357 14921-15074 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–4% MeOH in DCM) to give the desired compound as a colorless solid.
T358 15076-15328 Sentence denotes 4.1.14 9-[(2R,5R)-3-[2-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}(butyl)amino)ethoxy]-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-2-yl]-9H-purin-6-amine (23)
T359 15329-15447 Sentence denotes Following method D with 20 (80 mg, 97 μmol, 1.00 eq) and 1-bromobutane, 23 (40 mg, 47%) was obtained as a white solid.
T360 15448-15472 Sentence denotes Rf 0.48 (MeOH/DCM 5:95).
T361 15473-16089 Sentence denotes 1H NMR (600 MHz, CDCl3) δ 8.33 (s, 2H), 8.16 (s, 1H), 7.92 (s, 1H), 6.11 (d, J = 3.8 Hz, 1H), 6.03 (d, J = 2.3 Hz, 1H), 5.77 (br. s, 4H), 5.47 (dd, J = 6.4 Hz, J = 2.2 Hz, 1H), 4.91 (dd, J = 6.4 Hz, J = 3.2 Hz, 1H), 4.51 (t, J = 5.1 Hz, 1H), 4.37–4.24 (m, 2H), 4.09 (dt, J = 5.9 Hz, J = 3.0 Hz, 1H), 3.99 (dd, J = 11.5 Hz, J = 3.7 Hz, 1H), 3.76 (dd, J = 11.5 Hz, J = 2.8 Hz, 1H), 3.70–3.61 (m, 2H), 2.77–2.68 (m, 3H), 2.63 (dd, J = 13.5 Hz, J = 7.0 Hz, 1H), 2.46–2.37 (m, 2H), 1.59 (s, 3H), 1.38 (s, 3H), 1.31–1.22 (m, 2H), 1.22–1.12 (m, 2H), 0.92 (s, 9H), 0.91 (s, 9H), 0.82 (t, J = 7.3 Hz, 3H), 0.10–0.08 (m, 12H).
T362 16090-16349 Sentence denotes 13C NMR (150 MHz, CDCl3) δ 155.6, 155.5, 153.2, 153.1, 149.8, 149.4, 140.2, 139.7, 120.5, 120.3, 114.4, 91.2, 87.2, 85.8, 84.9, 84.0, 83.4, 82.4, 69.9, 69.3, 62.0, 56.7, 55.1, 53.9, 29.2, 27.2, 26.1, 25.9, 25.5, 20.5, 18.6, 18.2, 14.1, −4.4, −4.6, −5.2, −5.2.
T363 16350-16399 Sentence denotes HRMS (ESI+): m/z calcd for C46H72N11O7Si2 [M+H]+:
T364 16400-16416 Sentence denotes 884.4998, found:
T365 16417-16426 Sentence denotes 884.5002.
T366 16428-16689 Sentence denotes 4.1.15 9-[(2R,5R)-3-[2-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}(3-phenylpropyl)amino)ethoxy]-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-2-yl]-9H-purin-6-amine (24)
T367 16690-16821 Sentence denotes Following method D with 20 (120 mg, 0.15 mmol, 1.00 eq) and 1-bromo-3-phenylpropane, 24 (75 mg, 53%) was obtained as a white solid.
T368 16822-17731 Sentence denotes Rf 0.53 (MeOH/DCM 5:95).1H NMR (600 MHz, CDCl3) δ 8.31 (s, 1H), 8.28 (s, 1H), 8.15 (s, 1H), 7.90 (s, 1H), 7.25–7.08 (m, 5H), 6.11 (d, J = 3.7 Hz, 1H), 6.02 (d, J = 2.4 Hz, 1H), 5.81 (br. s, 4H), 5.46 (dd, J = 6.5 Hz, J = 2.1 Hz, 1H), 4.92 (dd, J = 6.5 Hz, J = 3.2 Hz, 1H), 4.50 (t, J = 5.1 Hz, 1H), 4.33–4.24 (m, 2H), 4.08 (dt, J = 5.9 Hz, J = 3.2 Hz, 1H), 3.98 (dd, J = 11.4 Hz, J = 3.6 Hz, 1H), 3.76 (dd, J = 11.5 Hz, J = 2.8 Hz, 1H), 3.72–3.60 (m, 2H), 2.80–2.70 (m, 3H), 2.64 (dd, J = 13.7 Hz, J = 6.7 Hz, 1H), 2.56–2.43 (m, 4H), 1.69–1.62 (m, 2H), 1.58 (s, 3H), 1.37 (s, 3H), 0.92 (s, 9H), 0.90 (s, 9H), 0.13–0.04 (m, 12H).13C NMR (150 MHz, CDCl3) δ 155.6, 155.5, 153.2, 153.1, 149.7, 149.4, 142.2, 140.2, 139.6, 128.4, 128.4, 125.8, 120.5, 120.3, 114.4, 91.1, 87.2, 85.7, 84.8, 83.9, 83.3, 82.5, 69.8, 69.3, 61.8, 56.7, 54.9, 53.9, 33.5, 28.8, 27.2, 26.1, 25.8, 25.5, 18.6, 18.2, −4.4, −4.6, −5.2, −5.2.
T369 17732-17781 Sentence denotes HRMS (ESI+): m/z calcd for C46H72N11O7Si2 [M+H]+:
T370 17782-17798 Sentence denotes 946.5155, found:
T371 17799-17808 Sentence denotes 946.5149.
T372 17810-18081 Sentence denotes 4.1.16 Methyl 4-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)amino)butanoate (25)
T373 18082-18213 Sentence denotes Following method D with 20 (600 mg, 0.73 mmol, 1.00 eq) and methyl-4-bromobutyrate, 25 (390 mg, 58%) was obtained as a white solid.
T374 18214-18238 Sentence denotes Rf 0.34 (MeOH/DCM 5:95).
T375 18239-18853 Sentence denotes 1H NMR (600 MHz, CDCl3) δ 8.32 (s, 1H), 8.31 (s, 1H), 8.17 (s, 1H), 7.90 (s, 1H), 6.11 (d, J = 3.6 Hz, 1H), 6.02 (m, 5H), 5.45 (dd, J = 6.5 Hz, J = 2.2 Hz, 1H), 4.91 (dd, J = 6.6 Hz, J = 3.3 Hz, 1H), 4.51 (t, J = 5.3 Hz, 1H), 4.32–4.23 (m, 2H), 4.08 (dt, J = 6.1 Hz, J = 3.2 Hz, 1H), 3.99 (dd, J = 11.5 Hz, J = 3.6 Hz, 1H), 3.76 (dd, J = 11.5 Hz, J = 2.8 Hz, 1H), 3.71–3.60 (m, 5H), 2.77 (dd, J = 13.5 Hz, J = 6.9 Hz, 1H), 2.74–2.69 (m, 2H), 2.64 (dd, J = 13.5 Hz, J = 6.8 Hz, 1H), 2.51–2.44 (m, 2H), 2.32–2.18 (m, 2H), 1.69–1.61 (m, 2H), 1.58 (s, 3H), 1.37 (s, 3H), 0.92 (s, 9H), 0.90 (s, 9H), 0.13–0.04 (m, 12H).
T376 18854-19120 Sentence denotes 13C NMR (150 MHz, CDCl3) δ 174.0, 155.7, 155.6, 153.2, 153.1, 149.7, 149.4, 140.1, 139.5, 120.5, 120.3, 114.4, 91.1, 87.2, 85.7, 84.8, 83.9, 83.3, 82.5, 69.8, 69.3, 61.9, 56.7, 54.3, 53.7, 51.6, 31.5, 27.2, 26.1, 25.8, 25.5, 22.6, 18.6, 18.2, −4.4, −4.6, −5.2, −5.2.
T377 19121-19170 Sentence denotes HRMS (ESI+): m/z calcd for C42H70N11O9Si2 [M+H]+:
T378 19171-19187 Sentence denotes 928.4897, found:
T379 19188-19197 Sentence denotes 928.4900.
T380 19199-19373 Sentence denotes 4.1.17 (2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)(butyl)amino]methyl}oxolane-3,4-diol (5)
T381 19374-20163 Sentence denotes Following method C with 23 (40 mg, 0.45 mol, 1.00 eq) and a 0–50% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 5 (20 mg, 72%) was obtained as a white powder with 98% purity determined by HPLC analysis at 260 nm.1H NMR (500 MHz, DMSO‑d 6) δ 8.36 (s, 1H), 8.32 (s, 1H), 8.14 (s, 1H), 8.13 (s, 1H), 7.33 (br. s, 2H), 7.25 (br. s, 2H), 5.97 (d, J = 6.3 Hz, 1H), 5.85 (d, J = 5.2 Hz, 1H), 5.49–5.39 (m, 3H), 5.14 (d, J = 5.3 Hz, 1H), 4.62 (q, J = 5.4 Hz, 1H), 4.52 (dd, J = 6.5, 4.7 Hz, 1H), 4.29 (dd, J = 4.8, 2.8 Hz, 1H), 4.06 (q, J = 4.9 Hz, 1H), 4.00–3.92 (m, 2H), 3.68–3.46 (m, 4H), 2.79 (dd, J = 14.0, 4.6 Hz, 1H), 2.70–2.51 (m, 3H), 2.41–2.30 (m, 2H), 1.22 (q, J = 7.4, 2H), 1.07 (tdd, J = 13.4 Hz, J = 10.5 Hz, J = 6.3 Hz, 2H), 0.73 (t, J = 7.3 Hz, 2H).
T382 20164-20359 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 156.2, 156.0, 152.6, 152.4, 149.3, 148.9, 139.8, 139.8, 119.3, 119.1, 87.5, 86.3, 86.2, 82.4, 81.2, 72.5, 71.9, 69.2, 67.9, 61.5, 56.1, 54.0, 53.7, 28.3, 19.8, 13.7.
T383 20360-20406 Sentence denotes HRMS (ESI+): m/z calcd for C26H38N11O7 [M+H]+:
T384 20407-20432 Sentence denotes 616.2956, Found 616.2955.
T385 20434-20617 Sentence denotes 4.1.18 (2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)(3-phenylpropyl)amino]methyl}oxolane-3,4-diol (6)
T386 20618-20862 Sentence denotes Following method C with 24 (40 mg, 0.42 μmol, 1.00 eq) and a 0–50% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 6 (8 mg, 28%) was obtained as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T387 20863-21408 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.36 (s, 1H), 8.32 (s, 1H), 8.14 (s, 1H), 8.13 (s, 1H), 7.33 (br. s, 2H), 7.25 (br. s, 2H), 5.97 (d, J = 6.3 Hz, 1H), 5.85 (d, J = 5.2 Hz, 1H), 5.49–5.39 (m, 3H), 5.14 (d, J = 5.3 Hz, 1H), 4.62 (q, J = 5.4 Hz, 1H), 4.52 (dd, J = 6.5, 4.7 Hz, 1H), 4.29 (dd, J = 4.8, 2.8 Hz, 1H), 4.06 (q, J = 4.9 Hz, 1H), 4.00–3.92 (m, 2H), 3.68–3.46 (m, 4H), 2.79 (dd, J = 14.0, 4.6 Hz, 1H), 2.70–2.51 (m, 3H), 2.41–2.30 (m, 2H), 1.22 (q, J = 7.4, 2H), 1.07 (tdd, J = 13.4 Hz, J = 10.5 Hz, J = 6.3 Hz, 2H), 0.73 (t, J = 7.3 Hz, 2H).
T388 21409-21604 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 156.1, 156.0, 152.5, 152.4, 149.3, 149.0, 139.8, 139.8, 119.3, 119.2, 87.6, 86.3, 86.2, 82.4, 81.2, 72.5, 71.9, 69.2, 68.0, 62.0, 56.2, 54.0, 53.7, 28.3, 19.8, 13.8.
T389 21605-21651 Sentence denotes HRMS (ESI+): m/z calcd for C26H38N11O7 [M+H]+:
T390 21652-21677 Sentence denotes 616.2956, Found 616.2955.
T391 21679-21872 Sentence denotes 4.1.19 Methyl 4-({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)amino)butanoate (7)
T392 21873-22119 Sentence denotes Following method C with 25 (116 mg, 0.13 mmol, 1.00 eq) and a 0–50% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 7 (51 mg, 60%) was obtained as a white powder with 97% purity determined by HPLC analysis at 260 nm.
T393 22120-22665 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.37 (s, 1H), 8.33 (s, 1H), 8.14 (s, 1H), 8.13 (s, 1H), 7.38 (br. s, 2H), 7.29 (br. s, 2H), 5.97 (d, J = 6.3 Hz, 1H), 5.84 (d, J = 5.3 Hz, 1H), 5.52–5.32 (m, 3H), 5.19 (d, J = 5.3 Hz, 1H), 4.62 (q, J = 5.4 Hz, 1H), 4.49 (dd, J = 6.3, 4.7 Hz, 1H), 4.30 (dd, J = 4.8, 2.8 Hz, 1H), 4.04 (q, J = 4.9 Hz, 1H), 3.99–3.96 (m, 1H), 3.95–3.87 (m, 1H), 3.66 (dt, J = 12.1, 4.1 Hz, 1H), 3.62–3.45 (m, 6H), 2.79 (dd, J = 14.1, 4.6 Hz, 1H), 2.71–2.52 (m, 3H), 2.45–2.28 (m, 2H), 2.14 (td, J = 7.4, 5.9 Hz, 2H), 1.58–1.46 (m, 2H).
T394 22666-22868 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 173.3, 156.2, 156.1, 152.6, 152.5, 149.4, 148.9, 139.9, 139.8, 119.4, 119.2, 87.6, 86.4, 86.3, 82.4, 81.3, 72.6, 71.9, 69.2, 68.0, 61.6, 56.3, 53.5, 53.4, 51.2, 30.9, 21.8.
T395 22869-22915 Sentence denotes HRMS (ESI+): m/z calcd for C27H38N11O9 [M+H]+:
T396 22916-22941 Sentence denotes 660.2854, Found 660.2855.
T397 22943-23132 Sentence denotes 4.1.20 4-({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}(2-[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)amino)butanoic acid (8)
T398 23133-23225 Sentence denotes Compound 25 (140 mg, 0.15 mmol, 1.00 eq) was treated with TFA (1.37 mL) and water (0.34 mL).
T399 23226-23287 Sentence denotes After stirring for 5.5 h, solvents were removed under vacuum.
T400 23288-23381 Sentence denotes The residue was dissolved in water (0.5 mL) and 2 M LiOH aqueous solution (3.5 mL) was added.
T401 23382-23484 Sentence denotes After stirring at 0 °C for 30 min, pH was adjusted to ≈3 or 4 by addition of 1 M HCl aqueous solution.
T402 23485-23708 Sentence denotes Solvents were removed under vacuum and the residue was purified by flash column chromatography on a reversed-phase silica gel column C18 (4 g, 40 μm) with a 0–20% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7.
T403 23709-23916 Sentence denotes The fractions containing the pure compound were pooled, concentrated and lyophilized with water and 1,4-dioxane to give 8 (35 mg, 36%) as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T404 23917-24327 Sentence denotes 1H NMR (600 MHz, D2O) δ 8.24 (s, 1H), 8.13 (s, 1H), 8.05 (s, 1H), 8.01 (s, 1H), 5.98 (d, J = 4.3 Hz, 1H), 5.94 (d, J = 4.6 Hz, 1H), 4.68–4.59 (m, 1H), 4.51–4.44 (m, 2H), 4.44–4.38 (m, 1H), 4.38–4.30 (m, 1H), 4.23–4.15 (m, 1H), 4.09–3.95 (m, 2H), 3.91 (dd, J = 12.9, J = 2.7 Hz, 1H), 3.80 (dd, J = 12.9, J = 3.8 Hz, 1H), 3.69–3.33 (m, 4H), 3.20 (m, 2H), 2.29 (td, J = 7.0 Hz, J = 2.7 Hz, 2H), 2.02–1.85 (m, 2H).
T405 24328-24517 Sentence denotes 13C NMR (150 MHz, D2O) δ 174.5, 154.9 (2C), 152.5, 152.3, 147.7, 147.5, 139.3, 138.5, 118.6, 118.3, 89.0, 86.9, 84.8, 81.8, 80.1, 73.9, 71.1, 69.0, 67.8, 60.3, 56.2, 55.3, 53.8, 52.5, 26.1.
T406 24518-24564 Sentence denotes HRMS (ESI+): m/z calcd for C26H37N12O9 [M+H]+:
T407 24565-24581 Sentence denotes 661.2806, found:
T408 24582-24591 Sentence denotes 661.2811.
T409 24593-24795 Sentence denotes 4.1.21 N-{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)-4-nitrobenzene-1-sulfonamide (9)
T410 24796-25038 Sentence denotes Using method C with 19 (100 mg, 97.4 μmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 9 (25 mg, 34%) was obtained as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T411 25039-25487 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.32 (s, 1H), 8.29 (s, 1H), 8.22–8.18 (m, 2H), 8.14 (s, 1H), 8.13 (s, 1H), 7.96–7.91 (m, 2H), 7.32 (br. s, 2H), 7.26 (br. s, 2H), 5.89 (d, J = 5.4 Hz, 1H), 5.79 (d, J = 5.6 Hz, 1H), 5.73–5.20 (m, 4H), 4.70 (t, J = 5.4 Hz, 1H), 4.34 (t, J = 5.1 Hz, 1H), 4.30–4.26 (m, 1H), 4.15 (t, J = 4.6 Hz, 1H), 4.09 (dt, J = 8.5 Hz, J = 4.3 Hz, 1H), 3.89 (q, J = 3.6 Hz, 1H), 3.75–3.70 (m, 2H), 3.66–3.63 (m, 1H), 3.60–3.29 (m, 5H).
T412 25488-25687 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 156.2, 156.2, 152.8, 152.7, 149.6, 149.3, 149.0, 145.0, 140.2, 139.6, 128.5, 124.3, 119.3, 119.3, 87.9, 86.3, 86.0, 82.9, 81.6, 72.5, 71.4, 70.0, 68.2, 61.2, 50.4, 47.5.
T413 25688-25736 Sentence denotes HRMS (ESI+): m/z calcd for C28H33N12O11S [M+H]+:
T414 25737-25762 Sentence denotes 745.2112, Found 745.2104.
T415 25764-25917 Sentence denotes 4.1.22 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-4-methoxy-2-nitrobenzene-1-sulfonamide (26)
T416 25918-26104 Sentence denotes Following method A with 5′-amino-2′,3′-isopropylidene adenosine (280 mg, 0.92 mmol, 1.00 eq) and 4-methoxy-2-nitrobenzenesufonyl chloride, 26 (191 mg, 40%) was obtained as a beige solid.
T417 26105-26129 Sentence denotes Rf 0.59 (8:92 MeOH/DCM).
T418 26130-26525 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.43 (t, J = 5.8 Hz, 1H), 8.28 (s, 1H), 8.12 (s, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.51 (d, J = 2.6 Hz, 1H), 7.40 (br. s, 2H), 7.20 (dd, J = 8.9 Hz, J = 2.6 Hz, 1H), 6.11 (d, J = 3.0 Hz, 1H), 5.36 (dd, J = 6.3 Hz, J = 3.0 Hz, 1H), 4.93 (dd, J = 6.4 Hz, J = 2.9 Hz, 1H), 4.23 (td, J = 5.8 Hz, J = 2.9 Hz, 1H), 3.87 (s, 3H), 3.27–3.14 (m, 2H), 1.52 (s, 3H), 1.28 (s, 3H).
T419 26526-26687 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 162.5, 156.2, 153.0, 149.0, 148.3, 140.2, 131.3, 123.8, 119.3, 117.2, 113.5, 109.8, 89.5, 84.1, 82.8, 81.5, 56.6, 44.5, 27.0, 25.1.
T420 26688-26734 Sentence denotes HRMS (ESI+): m/z calcd for C20H24N7O8S [M+H]+:
T421 26735-26760 Sentence denotes 522.1407, Found 522.1407.
T422 26762-26915 Sentence denotes 4.1.23 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-2-methoxy-4-nitrobenzene-1-sulfonamide (27)
T423 26916-27102 Sentence denotes Following method A with 5′-amino-2′,3′-isopropylidene adenosine (280 mg, 0.92 mmol, 1.00 eq) and 2-methoxy-4-nitrobenzenesufonyl chloride, 27 (200 mg, 42%) was obtained as a beige solid.
T424 27103-27127 Sentence denotes Rf 0.59 (8:92 MeOH/DCM).
T425 27128-27490 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.30 (t, J = 5.4 Hz, 1H), 8.23 (s, 1H), 8.12 (s, 1H), 7.88–7.82 (m, 2H), 7.77 (dd, J = 8.5 Hz, J = 2.2 Hz, 1H), 7.37 (br. s, 2H), 6.06 (d, J = 2.9 Hz, 1H), 5.31 (dd, J = 6.3 Hz, J = 3.0 Hz, 1H), 4.90 (dd, J = 6.4 Hz, J = 2.9 Hz, 1H), 4.16 (td, J = 5.7 Hz, J = 2.9 Hz, 1H), 3.88 (s, 3H), 3.24–3.12 (m, 2H), 1.49 (s, 3H), 1.27 (s, 3H).
T426 27491-27652 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 156.7, 156.2, 152.6, 150.8, 148.3, 140.1, 133.5, 130.3, 119.3, 114.8, 113.4, 107.7, 89.5, 84.2, 82.9, 81.5, 56.8, 44.7, 26.9, 25.1.
T427 27653-27699 Sentence denotes HRMS (ESI+): m/z calcd for C20H24N7O8S [M+H]+:
T428 27700-27725 Sentence denotes 522.1407, Found 522.1407.
T429 27727-27890 Sentence denotes 4.1.24 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-2-nitro-4-(trifluoromethyl)benzene-1-sulfonamide (28)
T430 27891-28047 Sentence denotes To a solution of 5′-amino-2′,3′-isopropylidene adenosine (280 mg, 0.92 mmol, 1.00 eq) in anhydrous DMF (4.6 mL) was added Et3N (250 μL, 1.83 mmol, 2.00 eq).
T431 28048-28221 Sentence denotes 2-nitro-4-trifluoromethylbenzenesufonyl chloride (396 mg, 1.37 mmol, 1.50 eq) was added at 0 °C and the reaction mixture was stirred for 4 h at room temperature under argon.
T432 28222-28292 Sentence denotes The reaction mixture was diluted with AcOEt (30 mL) and water (30 mL).
T433 28293-28462 Sentence denotes The aqueous layer was extracted with AcOEt (3 × 30 mL) and the combined organic extracts were washed with brine (30 mL), dried over Na2SO4 and concentrated under vacuum.
T434 28463-28611 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–5% MeOH in DCM) to give 28 (230 mg, 45%) as a dark red solid.
T435 28612-28639 Sentence denotes Rf 0.34 (8:92 MeOH/CH2Cl2).
T436 28640-29017 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.93 (t, J = 5.1 Hz, 1H), 8.50 (d, J = 1.8 Hz, 1H), 8.28 (s, 1H), 8.14 (s, 1H), 8.10 (dd, J = 1.6 Hz, J = 8.6 Hz, 1H), 8.04 (d, J = 8.3 Hz), 7.45 (br. s, 2H), 6.11 (d, J = 2.9 Hz, 1H), 5.34 (dd, J = 6.3 Hz, J = 2.9 Hz, 1H), 4.92 (dd, J = 6.3 Hz, J = 3.1 Hz, 1H), 4.20 (td, J = 5.9 Hz, J = 3.1 Hz, 1H), 3.37–3.25 (m, 2H), 1.50 (s, 3H), 1.27 (s, 3H).
T437 29018-29236 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 156.1, 152.4, 148.4, 147.6, 140.2, 136.4, 133.8, 133.5, 133.2, 133.0, 130.8, 129.4, 125.5, 123.4, 121.2, 119.0, 122.0, 122.0, 119.3, 113.5, 107.7, 89.4, 84.3, 83.0, 81.5, 44.7, 26.9, 25.0.
T438 29237-29285 Sentence denotes HRMS (ESI+): m/z calcd for C20H21N7O7SF3 [M+H]+:
T439 29286-29311 Sentence denotes 560.1175, Found 560.1180.
T440 29313-29465 Sentence denotes 4.1.25 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-4-chloro-3-nitrobenzene-1-sulfonamide (29)
T441 29466-29651 Sentence denotes Following method A with 5′-amino-2′,3′-isopropylidene adenosine (280 mg, 0.92 mmol, 1.00 eq) and 4-chloro-3-nitrobenzenesufonyl chloride, 29 (346 mg, 72%) was obtained as a brown solid.
T442 29652-29679 Sentence denotes Rf 0.42 (8:92 MeOH/CH2Cl2).
T443 29680-30048 Sentence denotes 1H NMR (400 MHz, DMSO‑d 6) δ 8.56 (s, 1H), 8.39 (d, J = 2.1 Hz, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 7.96 (dd, J = 8.5 Hz, J = 2.1 Hz, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.37 (br. s, 2H), 6.12 (d, J = 2.8 Hz, 1H), 5.34 (dd, J = 6.3 Hz, J = 2.9 Hz, 1H), 4.89 (dd, J = 6.3 Hz, J = 3.1 Hz, 1H) 4.17 (td, J = 5.9 Hz, J = 3.0 Hz, 1H), 3.33–3.18 (m, 2H), 1.51 (s, 3H), 1.29 (s, 3H).
T444 30049-30211 Sentence denotes 13C NMR (100 MHz, DMSO‑d 6) δ 156.7, 153.0, 148.9, 147.8, 141.1, 140.6, 133.4, 131.6, 129.8, 124.4, 119.7, 114.0, 107.7, 89.8, 84.7, 83.4, 82.0, 44.9, 27.4, 25.6.
T445 30212-30260 Sentence denotes HRMS (ESI+): m/z calcd for C19H21N7O7SCl [M+H]+:
T446 30261-30286 Sentence denotes 526.0912, Found 526.0914.
T447 30288-30578 Sentence denotes 4.1.26 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)-4-methoxy-2-nitrobenzene-1-sulfonamide (30)
T448 30579-30688 Sentence denotes Following method B with 26 (161 mg, 0.31 mmol, 1.00 eq), 30 (166 mg, 52%) was obtained as a pale white solid.
T449 30689-30714 Sentence denotes Rf 0.67 (10:90 MeOH/DCM).
T450 30715-31296 Sentence denotes 1H NMR (500 MHz, CDCl3)) δ 8.286 (s, 1H), 8.292 (s, 1H), 8.14 (s, 1H), 7.82 (s, 1H), 7.66 (d, J = 8.9 Hz, 1H), 6.92 (d, J = 2.6 Hz, 1H), 6.74 (dd, J = 9.0 Hz, J = 2.6 Hz, 1H), 6.01 (d, J = 3.2 Hz, 1H), 5.97–5.88 (m, 5H), 5.31 (dd, J = 6.5 Hz, J = 2.1 Hz, 1H), 4.99 (dd, J = 6.4 Hz, J = 3.7 Hz, 1H), 4.52 (dd, J = 6.1 Hz, J = 4.6 Hz, 1H), 4.43 (dt, J = 8.4 Hz, J = 4.2 Hz, 1H), 4.22 (dd, J = 4.7 Hz, J = 3.2 Hz, 1H), 4.06 (dt, J = 6.1 Hz, J = 3.1 Hz, 1H), 3.97 (dd, J = 11.5 Hz, J = 3.5 Hz, 1H), 3.86–3.49 (m, 10H), 1.55 (s, 3H), 1.33 (s, 3H), 0.90 (br. s, 18H), 0.11–0.05 (m, 12H).
T451 31297-31573 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 162.8, 155.7, 155.5, 153.2, 152.9, 149.6, 149.1, 149.0, 140.2, 139.7, 133.0, 125.0, 120.4, 120.3, 116.2, 114.7, 109.9, 90.6, 87.4, 84.5, 84.5 (2C), 84.3, 82.6, 82.5, 69.9, 69.6, 61.6, 50.2, 47.2, 27.3, 26.2, 25.9, 25.4, 18.6, 18.2, −4.4, −4.7, −5.3.
T452 31574-31625 Sentence denotes HRMS (ESI+): m/z calcd for C47H67N12O12SSi2 [M+H]+:
T453 31626-31643 Sentence denotes 1043.4261, found:
T454 31644-31654 Sentence denotes 1043.4265.
T455 31656-31946 Sentence denotes 4.1.27 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)-2-methoxy-4-nitrobenzene-1-sulfonamide (31)
T456 31947-32056 Sentence denotes Following method B with 27 (185 mg, 0.36 mmol, 1.00 eq), 31 (160 mg, 43%) was obtained as a pale white solid.
T457 32057-32082 Sentence denotes Rf 0.67 (10:90 MeOH/DCM).
T458 32083-32580 Sentence denotes 1H NMR (500 MHz, CDCl3) δ 8.30 (s, 1H), 8.29 (s, 1H), 8.16 (br. s, 1H), 7.82 (s, 1H), 7.67 (m, 2H), 7.57–7.43 (m, 2H), 6.16–5.90 (m, 5H), 5.88 (s, 1H), 5.27 (br. s, 1H), 4.94 (dd, J = 6.7 Hz, J = 3.7 Hz, 1H), 4.52 (t, J = 5.4 Hz, 1H), 4.42 (dt, J = 8.7 Hz, J = 4.2 Hz, 1H), 4.20 (dd, J = 4.7 Hz, J = 3.1 Hz, 1H), 4.07 (dt, J = 6.1 Hz, J = 3.0 Hz, 1H), 3.99 (dd, J = 11.5 Hz, J = 3.4 Hz, 1H), 3.92–3.44 (m, 10H), 1.54 (s, 3H), 1.32 (s, 3H), 0.921 (br. s, 9H), 0.918 (br. s, 9H), 0.15–0.05 (m, 12H).
T459 32581-32856 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 157.1, 155.8, 155.5, 153.2, 152.9, 150.9, 149.5, 148.9, 139.7, 139.6, 134.2, 131.5, 120.4, 120.2, 114.7 (2C), 106.7, 90.5, 87.5, 84.5, 84.4, 84.4, 82.8, 82.6, 70.7, 69.6, 61.5, 56.8, 50.2, 47.1, 27.2, 26.2, 25.9, 25.4, 18.6, 18.2, −4.3, −4.8, −5.2.
T460 32857-32908 Sentence denotes HRMS (ESI+): m/z calcd for C47H67N12O12SSi2 [M+H]+:
T461 32909-32926 Sentence denotes 1043.4261, found:
T462 32927-32937 Sentence denotes 1043.4255.
T463 32939-33239 Sentence denotes 4.1.28 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)-2-nitro-4-(trifluoromethyl)benzene-1-sulfonamide (32)
T464 33240-33347 Sentence denotes Following method B with 28 (77 mg, 0.14 mmol, 1.00 eq), 32 (68 mg, 46%) was obtained as a pale white solid.
T465 33348-33373 Sentence denotes Rf 0.47 (10:90 MeOH/DCM).
T466 33374-33984 Sentence denotes 1H NMR (500 MHz, CDCl3) δ 8.33 (s, 1H), 8.30 (s, 1H), 8.15 (s, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 1.7 Hz, 1H), 7.76 (s, 1H), 7.54 (dd, J = 8.4 Hz, J = 1.8 Hz, 1H), 5.97 (d, J = 2.8 Hz, 1H), 5.93 (d, J = 1.9 Hz, 1H), 5.74 (br. s, 4H), 5.33 (dd, J = 6.4 Hz, J = 2.0 Hz, 1H), 5.01 (dd, J = 6.4 Hz, J = 3.8 Hz, 1H), 4.50 (dd, J = 6.4 Hz, J = 4.6 Hz, 1H), 4.43 (dt, J = 8.3 Hz, J = 4.0 Hz, 1H), 4.18 (dd, J = 4.7 Hz, J = 2.8 Hz, 1H), 4.01–3.96 (m, 2H), 3.94–3.78 (m, 4H), 3.77–3.66 (m, 2H), 3.56 (dt, J = 15.5 Hz, J = 5.1 Hz, 1H), 1.55 (s, 3H), 1.34 (s, 3H), 0.91 (s, 9H), 0.89 (s, 9H), 0.13–0.02 (m, 12H).
T467 33985-34340 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 155.6, 155.4, 153.3, 153.0, 149.5, 149.1, 147.9, 140.2, 139.5, 137.4, 135.6, 135.3, 135.0, 134.7, 132.0, 128.3, 128.3, 125.3, 123.2, 121.0, 118.8, 121.7, 121.6, 133.0, 120.4, 120.3, 116.2, 114.8, 109.9, 90.6, 87.5, 84.7, 84.3, 84.1, 82.9, 82.6, 69.6, 69.4, 61.3, 50.2, 47.4, 27.2, 26.2, 25.9, 25.4, 18.6, 18.2, −4.4, −4.8, −5.3.
T468 34341-34394 Sentence denotes HRMS (ESI+): m/z calcd for C44H64N12O11SF3Si2 [M+H]+:
T469 34395-34412 Sentence denotes 1081.4029, found:
T470 34413-34423 Sentence denotes 1081.4034.
T471 34425-34714 Sentence denotes 4.1.29 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)-4-chloro-3-nitrobenzene-1-sulfonamide (33)
T472 34715-34824 Sentence denotes Following method B with 29 (230 mg, 0.44 mmol, 1.00 eq), 33 (160 mg, 43%) was obtained as a pale white solid.
T473 34825-34850 Sentence denotes Rf 0.52 (10:90 MeOH/DCM).
T474 34851-35387 Sentence denotes 1H NMR (600 MHz, CDCl3) δ 8.29 (s, 1H), 8.28 (s, 1H), 8.116 (2s, 2H), 7.79 (s, 1H), 7.65 (dd, J = 8.4 Hz, J = 2.1 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 6.02–5.93 (m, 6H), 5.36 (dd, J = 6.4 Hz, J = 1.8 Hz, 1H), 5.05 (dd, J = 6.4 Hz, J = 3.8 Hz, 1H), 4.51 (dd, J = 6.1 Hz, J = 4.7 Hz, 1H), 4.44 (dt, J = 8.5 Hz, J = 4.3 Hz, 1H), 4.19 (dd, J = 4.7 Hz, J = 3.0 Hz, 1H), 4.05–3.97 (m, 2H), 3.82 (t, J = 5.5 Hz, 2H), 3.79–3.65 (m, 3H), 3.46 (q, J = 5.3 Hz, 2H), 1.56 (s, 3H), 1.35 (s, 3H), 0.92 (br. s, 9H), 0.90 (br. s, 9H), 0.12–0.05 (m, 12H).
T475 35388-35658 Sentence denotes 13C NMR (150 MHz, CDCl3) δ 155.8, 155.6, 153.2, 153.1, 149.5, 149.0, 147.6, 140.3, 140.2, 139.4, 132.4, 131.3, 131.2, 124.6, 120.5, 120.2, 114.7, 90.7, 87.4, 85.0, 84.3 (2C), 82.9, 82.6, 69.7, 69.5, 61.4, 50.5, 47.7, 27.2, 26.2, 25.9, 25.4, 18.6, 18.2, −4.4, −4.7, −5.2.
T476 35659-35712 Sentence denotes HRMS (ESI+): m/z calcd for C43H64N12O11SSi2Cl [M+H]+:
T477 35713-35730 Sentence denotes 1047.3765, found:
T478 35731-35741 Sentence denotes 1047.3766.
T479 35743-35983 Sentence denotes 4.1.30 N-(((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-N-(2-(((2R,3R,4R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl)oxy)ethyl)-4-methoxy-2-nitrobenzenesulfonamide (10)
T480 35984-36227 Sentence denotes Using method C with 30 (167 mg, 0.16 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 10 (25 mg, 20%) was obtained as a white powder with 97% purity determined by HPLC analysis at 260 nm.
T481 36228-36738 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.32 (s, 1H), 8.28 (s, 1H), 8.13 (s, 2H), 7.77 (d, J = 9.0 Hz, 1H), 7.44 (dd, J = 8.5 Hz, J = 2.6 Hz, 1H), 7.34 (br. s, 2H), 7.29 (br. s, 2H), 6.99 (dd, J = 9.0 Hz, J = 2.6 Hz, 1H), 5.95 (d, J = 5.2 Hz, 1H), 5.83 (d, J = 5.5 Hz, 1H), 5.65 (br. s, 1H), 5.49 (br. s, 1H), 5.38 (t, J = 5.7 Hz, 1H), 5.27 (br. s, 1H), 4.66 (t, J = 5.2 Hz, 1H), 4.37 (t, J = 5.1 Hz, 1H), 4.33–4.26 (m, 1H), 4.17–4.08 (m, 2H), 3.93 (q, J = 3.6 Hz, 1H), 3.84 (s, 3H), 3.80–3.62 (m, 3H), 3.60–3.37 (m, 5H).
T482 36739-36956 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 162.6, 156.1, 156.2, 152.6, 152.6, 149.3, 149.0, 148.9, 139.9, 139.8, 131.5, 123.3, 119.2 (2C), 116.7, 109.7, 87.8, 86.3, 85.8, 81.8, 81.5, 72.5, 71.5, 68.1, 66.4, 61.1, 56.6, 50.3, 47.1.
T483 36957-37005 Sentence denotes HRMS (ESI+): m/z calcd for C29H35N12O12S [M+H]+:
T484 37006-37031 Sentence denotes 775.2218, Found 775.2225.
T485 37033-37246 Sentence denotes 4.1.31 N-{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)-2-methoxy-4-nitrobenzene-1-sulfonamide (11)
T486 37247-37490 Sentence denotes Using method C with 31 (160 mg, 0.15 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 11 (15 mg, 13%) was obtained as a white powder with 98% purity determined by HPLC analysis at 260 nm.
T487 37491-38001 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.32 (s, 1H), 8.28 (s, 1H), 8.13 (s, 2H), 7.77 (d, J = 9.0 Hz, 1H), 7.44 (dd, J = 8.5 Hz, J = 2.6 Hz, 1H), 7.34 (br. s, 2H), 7.29 (br. s, 2H), 6.99 (dd, J = 9.0 Hz, J = 2.6 Hz, 1H), 5.95 (d, J = 5.2 Hz, 1H), 5.83 (d, J = 5.5 Hz, 1H), 5.65 (br. s, 1H), 5.49 (br. s, 1H), 5.38 (t, J = 5.7 Hz, 1H), 5.27 (br. s, 1H), 4.66 (t, J = 5.2 Hz, 1H), 4.37 (t, J = 5.1 Hz, 1H), 4.33–4.27 (m, 1H), 4.17–4.08 (m, 2H), 3.93 (q, J = 3.6 Hz, 1H), 3.84 (s, 3H), 3.80–3.62 (m, 3H), 3.60–3.37 (m, 5H).
T488 38002-38221 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 156.9, 156.1, 155.9, 152.5, 152.4, 150.6, 149.0, 148.8, 134.0, 139.5, 133.7, 131.0, 119.2, 119.2, 114.4, 107.4, 87.8, 86.2, 85.9, 81.5, 81.4, 72.5, 71.3, 68.9, 66.7, 61.1, 56.8, 50.2, 47.1.
T489 38222-38270 Sentence denotes HRMS (ESI+): m/z calcd for C29H35N12O12S [M+H]+:
T490 38271-38296 Sentence denotes 775.2218, Found 775.2220.
T491 38298-38521 Sentence denotes 4.1.32 N-{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)-2-nitro-4-(trifluoromethyl)benzene-1-sulfonamide (12)
T492 38522-38762 Sentence denotes Using method C with (120 mg, 0.11 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 12 (18 mg, 20%) was obtained as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T493 38763-39304 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.47 (d, J = 1.7 Hz, 1H), 8.32 (s, 1H), 8.28 (s, 1H), 8.15 (d, J = 8.3 Hz, 1H), 8.12 (s, 1H), 8.11 (s, 1H), 7.88 (dd, J = 8.6 Hz, J = 1.8 Hz, 1H), 7.36 (br. s, 2H), 7.31 (br. s, 2H), 5.90 (d, J = 5.2 Hz, 1H), 5.82 (d, J = 5.4 Hz, 1H), 5.61 (d, J = 6.0 Hz, 1H), 5.43 (d, J = 5.1 Hz, 1H), 5.38 (dd, J = 6.6 Hz, J = 4.8 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 4.65 (q, J = 5.4 Hz, 1H), 4.37 (t, J = 5.1 Hz, 1H), 4.31 (q, J = 4.7 Hz, 1H), 4.19–4.10 (m, 2H), 3.91 (q, J = 3.6 Hz, 1H), 3.87–3.63 (m, 4H), 3.61–3.45 (m, 4H).
T494 39305-39579 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 156.2, 156.1, 152.7, 152.6, 149.2, 148.9, 147.7, 139.9, 139.4, 135.9, 133.9, 133.6, 133.3, 133.1, 131.1, 128.9, 128.9, 152.5, 123.3, 121.1, 119.0, 122.0, 121.9, 119.2 (2C), 87.8, 86.3, 85.9, 81.6, 81.5, 72.5, 71.4, 68.8, 67.7, 61.0, 50.0, 47.3.
T495 39580-39617 Sentence denotes 19F NMR (378 MHz, DMSO‑d 6): δ −62.8.
T496 39618-39668 Sentence denotes HRMS (ESI+): m/z calcd for C29H32N12O11SF3 [M+H]+:
T497 39669-39694 Sentence denotes 813.1986, Found 813.1988.
T498 39696-39908 Sentence denotes 4.1.33 N-{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)-4-chloro-3-nitrobenzene-1-sulfonamide (13)
T499 39909-40152 Sentence denotes Using method C with 33 (121 mg, 0.12 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 13 (14 mg, 16%) was obtained as a white powder with 98% purity determined by HPLC analysis at 260 nm.
T500 40153-40689 Sentence denotes 1H NMR (500 MHz, DMSO‑d 6) δ 8.42 (d, J = 2.2 Hz, 1H), 8.34 (s, 1H), 8.32 (s, 1H), 8.144 (s, 1H), 8.140 (s, 1H), 7.96 (dd, J = 8.5 Hz, J = 2.2 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), 7.41 (br. s, 2H) 7.35 (br. s, 2H), 5.90 (d, J = 5.2 Hz, 1H), 5.83 (d, J = 5.8 Hz, 1H), 5.59 (d, J = 6.0 Hz, 1H), 5.48–5.31 (m, 2H), 5.25 (d, J = 5.3 Hz, 1H), 4.72 (q, J = 5.5 Hz, 1H), 4.36 (t, J = 5.0 Hz, 1H), 4.29 (q, J = 4.6 Hz, 1H), 4.22–4.08 (m, 2H), 3.87 (q, J = 3.6 Hz, 1H), 3.78–3.70 (m, 2H), 3.67 (dd, J = 12.2 Hz, J = 3.4 Hz, 1H), 3.56–3.29 (m, 5H).
T501 40690-40903 Sentence denotes 13C NMR (125 MHz, DMSO‑d 6) δ 156.1, 156.0, 152.6, 152.5, 149.3, 148.9, 147.4, 140.1, 139.5, 139.5, 132.7, 131.6, 129.6, 124.3, 119.3, 119.3, 87.6, 86.2, 85.8, 81.8, 81.5, 72.3, 71.3, 68.8, 68.1, 61.4, 50.8, 48.1.
T502 40904-40954 Sentence denotes HRMS (ESI+): m/z calcd for C28H32N12O11SCl [M+H]+:
T503 40955-40980 Sentence denotes 779.1723, Found 779.1730.
T504 40982-41263 Sentence denotes 4.1.34 N-{[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-3-yl]oxy}ethyl)-4-chlorobenzene-1-sulfonamide (34)
T505 41264-41380 Sentence denotes To a solution of 20 (171 mg, 0.21 mmol, 1.00 eq) in anhydrous DCM (2 mL) was added Et3N (60 μL, 0.41 mmol, 2.00 eq).
T506 41381-41537 Sentence denotes 4-chlorobenzenesulfonyl chloride (65 mg, 0.31 mmol, 1.50 eq) was added at 0 °C and the reaction mixture was stirred for 3 h at room temperature under argon.
T507 41538-41667 Sentence denotes Solvents were removed under vacuum and the residue was diluted with DCM (40 mL) and washed with saturated aqueous NaHCO3 (40 mL).
T508 41668-41835 Sentence denotes The aqueous layer was extracted with DCM (3 × 30 mL) and the combined organic extracts were washed with brine (30 mL), dried over Na2SO4 and concentrated under vacuum.
T509 41836-41981 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–4% MeOH in DCM) to give 34 (188 mg, 90%) as a white solid.
T510 41982-42010 Sentence denotes Rf 0.67 (10:90 MeOH/CH2Cl2).
T511 42011-42583 Sentence denotes 1H NMR (500 MHz, CDCl3) δ 8.32 (s, 1H), 8.29 (s, 1H), 8.12 (s, 1H), 7.81 (s, 1H), 7.59–7.46 (m, 2H), 7.34–7.22 (m, 2H), 5.97 (d, J = 3.3 Hz, 1H), 5.96–5.88 (m, 5H), 5.41 (dd, J = 6.4 Hz, J = 2.0 Hz, 1H), 5.07 (dd, J = 6.4 Hz, J = 3.5 Hz, 1H), 4.50 (dd, J = 5.9 Hz, J = 4.6 Hz, 1H), 4.46–4.34 (m, 1H), 4.21 (dd, J = 4.7 Hz, J = 3.3 Hz, 1H), 4.03 (dt, J = 6.0 Hz, J = 3.0 Hz, 1H), 3.98 (dd, J = 11.4 Hz, J = 3.5 Hz, 1H), 3.80–3.72 (m, 3H), 3.68 (dd, J = 14.6 Hz, J = 5.6 Hz, 1H), 3.46–3.31 (m, 3H), 1.57 (s, 3H), 1.36 (s, 3H), 0.91 (s, 9H), 0.89 (s, 9H), 0.11–0.03 (m, 12H).
T512 42584-42839 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 155.8, 155.6, 153.2, 153.1, 149.5, 149.1, 140.2, 139.5, 139.1, 138.0, 129.2, 128.6, 120.5, 120.2, 114.6, 90.9, 87.3, 85.3, 84.5, 84.1, 82.6 (2C), 69.6 (2C), 61.6, 50.7, 48.1, 27.2, 26.1, 25.9, 25.4, 18.6, 18.2, −4.5, −4.7, −5.3.
T513 42840-42892 Sentence denotes HRMS (ESI+): m/z calcd for C43H65N11O9SSi2Cl [M+H]+:
T514 42893-42910 Sentence denotes 1002.3909, found:
T515 42911-42921 Sentence denotes 1002.3928.
T516 42923-43200 Sentence denotes 4.1.35 9-[(2R,5R)-3-[2-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}[(4-chloro-3-nitrophenyl)methyl]amino)ethoxy]-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-2-yl]-9H-purin-6-amine (35)
T517 43201-43428 Sentence denotes To a solution of 20 (100 mg, 0.12 mmol, 1.00 eq) in anhydrous DCE (3.5 mL) was added a solution of 4-chloro-3-nitrobenazaldehyde (27 mg, 0.18 mmol, 1.50 eq) in anhydrous DCE (3.5 mL) and acetic acid (10 μL, 0.18 mmol, 1.50 eq).
T518 43429-43544 Sentence denotes After stirring for 20 min at 40 °C under argon, sodium triacetoxyborohydride (38 mg, 0.18 mmol, 1.50 eq) was added.
T519 43545-43662 Sentence denotes After stirring at 40 °C for 16 h, the solution was diluted with DCM (30 mL) and washed with saturated aqueous NaHCO3.
T520 43663-43830 Sentence denotes The aqueous layer was extracted with DCM (3 × 30 mL) and the combined organic extracts were washed with brine (60 mL), dried over Na2SO4 and concentrated under vacuum.
T521 43831-43976 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–5% MeOH in DCM) to give 35 as a white solid (105 mg, 87%).
T522 43977-44001 Sentence denotes Rf 0.71 (MeOH/DCM 5:95).
T523 44002-44598 Sentence denotes 1H NMR (500 MHz, CDCl3) δ 8.27 (s, 1H), 8.18 (s, 1H), 8.15 (s, 1H), 7.82 (br. s, 2H), 7.29–7.27 (m, 2H), 6.22 (br. s, 2H), 6.20 (br. s, 2H), 6.10 (d, J = 3.6 Hz, 1H), 5.99 (d, J = 2.1 Hz, 1H), 5.37 (dd, J = 6.5 Hz, J = 2.1 Hz, 1H), 4.91 (dd, J = 6.5 Hz, J = 3.7 Hz, 1H), 4.48 (t, J = 5.1 Hz, 1H), 4.30 (td, J = 6.7 Hz, J = 3.6 Hz, 1H), 4.22 (t, J = 4.2 Hz, 1H), 4.07 (dt, J = 5.8 Hz, J = 3.0 Hz, 1H), 3.99 (dd, J = 11.5 Hz, J = 3.4 Hz, 1H), 3.81–3.72 (m, 2H), 3.71–3.66 (m, 1H), 3.65–3.61 (m, 2H), 2.90–2.70 (m, 4H), 1.57 (s, 3H), 1.36 (s, 3H), 0.92 (s, 9H), 0.86 (s, 9H), 0.14 – - 0.02 (m, 12H).
T524 44599-44882 Sentence denotes 13C NMR (125 MHz, CDCl3) δ 155.8, 155.7, 153.1, 153.0, 149.6, 149.0, 147.8, 140.6, 140.1, 139.3, 133.0, 131.4, 125.6, 125.2, 120.3, 120.1, 114.6, 90.8, 87.0, 85.7, 84.9, 84.0, 83.4, 82.8, 69.6, 69.3, 61.8, 58.2, 56.4, 53.5, 27.2, 26.2, 25.8, 25.4, 18.6, 18.2, −4.5, −4.7, −5.2, −5.3.
T525 44883-44934 Sentence denotes HRMS (ESI+): m/z calcd for C44H66N12O9Si2Cl [M+H]+:
T526 44935-44951 Sentence denotes 997.4297, found:
T527 44952-44961 Sentence denotes 997.4327.
T528 44963-45232 Sentence denotes 4.1.36 9-[(2R,5R)-3-[2-({[(4R,6R)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d] [1,3]dioxol-4-yl]methyl}[(4-chlorophenyl)methyl]amino)ethoxy]-4-[(tert-butyldimethylsilyl)oxy]-5-{[(tert-butyldimethylsilyl)oxy]methyl}oxolan-2-yl]-9H-purin-6-amine (36)
T529 45233-45433 Sentence denotes To a solution of 20 (210 mg, 0.25 mmol, 1.00 eq) in anhydrous DCE (7 mL) was added 4-chlorobenzaldehyde (43 mg, 0.38 mmol, 1.50 eq) in anhydrous DCE (7 mL) and acetic acid (18 μL, 0.38 mmol, 1.50 eq).
T530 45434-45549 Sentence denotes After stirring for 20 min at 40 °C under argon, sodium triacetoxyborohydride (81 mg, 0.38 mmol, 1.50 eq) was added.
T531 45550-45667 Sentence denotes After stirring at 40 °C for 16 h, the solution was diluted with DCM (50 mL) and washed with saturated aqueous NaHCO3.
T532 45668-45835 Sentence denotes The aqueous layer was extracted with DCM (3 × 50 mL) and the combined organic extracts were washed with brine (70 mL), dried over Na2SO4 and concentrated under vacuum.
T533 45836-45992 Sentence denotes The residue was purified by flash column chromatography (silica gel, linear gradient 0–5% MeOH in DCM) to give 36 as a white solid (172 mg, 0.18 mmol, 72%).
T534 45993-46020 Sentence denotes Rf 0.71 (MeOH/CH2Cl2 5:95).
T535 46021-46554 Sentence denotes 1H NMR (600 MHz, CDCl3) δ 8.30 (s, 1H), 8.20 (s, 1H), 8.15 (s, 1H), 7.83 (s, 1H), 7.19–7.07 (m, 4H), 6.11 (d, J = 3.7 Hz, 1H), 5.99 (d, J = 2.2 Hz, 1H), 5.97–5.83 (m, 4H), 5.37 (dd, J = 6.5 Hz, J = 2.2 Hz, 1H), 4.85 (dd, J = 6.4 Hz, J = 3.4 Hz, 1H), 4.49 (t, J = 5.1 Hz, 1H), 4.32 (td, J = 6.7 Hz, J = 3.3 Hz, 1H), 4.26 (t, J = 4.2 Hz, 1H), 4.08 (dt, J = 5.9 Hz, J = 3.1 Hz, 1H), 3.98 (dd, J = 11.5 Hz, J = 3.6 Hz, 1H), 3.79–3.47 (m, 5H), 2.84–2.66 (m, 4H), 1.58 (s, 3H), 1.36 (s, 3H), 0.92 (s, 9H), 0.88 (s, 9H), 0.13–0.02 (m, 12H).
T536 46555-46824 Sentence denotes 13C NMR (150 MHz, CDCl3) δ 155.7, 155.6, 153.1, 153.1, 149.7, 149.3, 140.0, 139.5, 137.8, 132.8, 130.1, 128.4, 120.5, 120.3, 114.4, 91.0, 87.2, 85.7, 84.9, 84.0, 83.5, 82.7, 69.8, 69.5, 61.3, 58.6, 56.4, 53.6, 27.3, 26.2, 25.9, 25.5, 18.6, 18.2, −4.5, −4.7, −5.2, −5.3.
T537 46825-46876 Sentence denotes HRMS (ESI+): m/z calcd for C44H67N11O7Si2Cl [M+H]+:
T538 46877-46893 Sentence denotes 952.4447, found:
T539 46894-46903 Sentence denotes 952.4426.
T540 46905-47109 Sentence denotes 4.1.37 N-{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}-N-(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)-4-chlorobenzene-1-sulfonamide (14)
T541 47110-47353 Sentence denotes Using method C with 34 (150 mg, 0.15 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 14 (55 mg, 48%) was obtained as a white powder with 96% purity determined by HPLC analysis at 260 nm.
T542 47354-47874 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.33 (s, 1H), 8.32 (s, 1H), 8.150 (s, 1H), 8.147 (s, 1H), 7.75–7.68 (m, 2H), 7.53–7.49 (m, 2H), 7.35 (br. s, 2H), 7.28 (br. s, 2H), 5.95 (d, J = 5.5 Hz, 1H), 5.84 (d, J = 5.9 Hz, 1H), 5.52 (d, J = 6.1 Hz, 1H), 5.36 (m, 2H), 5.20 (d, J = 5.2 Hz, 1H), 4.74 (q, J = 5.6 Hz, 1H), 4.39 (t, J = 5.2 Hz, 1H), 4.29 (q, J = 4.7 Hz, 1H), 4.16 (q, J = 4.6 Hz, 1H), 4.11–4.05 (m, 1H), 3.93 (q, J = 3.6 Hz, 1H), 3.73–3.64 (m, 3H), 3.56–3.46 (m, 2H), 3.37–3.29 (m, 3H), 3.22 (dt, J = 14.7 Hz, 6.4 Hz, 1H).
T543 47875-48074 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 156.1, 156.0, 152.5, 152.5, 149.3, 148.9, 140.1, 139.5, 138.0, 137.7, 129.2, 128.7, 119.3, 119.3, 87.7, 86.2, 85.9, 82.1, 81.4, 72.2, 71.3, 69.9, 68.3, 61.1, 50.8, 47.7.
T544 48075-48124 Sentence denotes HRMS (ESI+): m/z calcd for C28H33N11O9SCl [M+H]+:
T545 48125-48150 Sentence denotes 734.1868, Found 734.1866.
T546 48152-48352 Sentence denotes 4.1.38 (2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)[(4-chloro-3-nitrophenyl)methyl]amino]methyl}oxolane-3,4-diol (15)
T547 48353-48596 Sentence denotes Using method C with 35 (140 mg, 0.14 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 15 (25 mg, 25%) was obtained as a white powder with 99% purity determined by HPLC analysis at 260 nm.
T548 48597-49188 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.35 (s, 1H), 8.23 (s, 1H), 8.11 (s, 1H), 8.07 (s, 1H), 7.89 (d, J = 1.9 Hz, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.45 (dd, J = 8.3 Hz, J = 2.0 Hz, 1H), 7.32 (br. s, 2H), 7.24 (br. s, 2H), 5.99 (d, J = 5.9 Hz, 1H), 5.83 (d, J = 5.1 Hz, 1H), 5.51–5.32 (m, 2H), 5.24 (br. s, 1H), 5.13 (br. s, 1H), 4.57 (t, J = 5.2 Hz, 1H), 4.45 (dd, J = 6.1 Hz, J = 4.8 Hz, 1H), 4.30 (t, J = 4.1 Hz, 1H), 4.05 (t, J = 5.0 Hz, 1H), 4.02–3.95 (m, 2H), 3.73–3.63 (m, 4H), 3.58–3.51 (m, 2H), 2.83 (dd, J = 14.0 Hz, J = 4.4 Hz, 1H), 2.73 (dd, J = 14.0 Hz, J = 7.2 Hz, 1H), 2.69–2.63 (m, 2H).
T549 49189-49406 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 156.1, 156.0, 152.5 (2C), 149.3, 148.9, 147.2, 140.1, 139.8, 139.6, 133.7, 131.0, 125.0, 122.9, 119.3, 119.2, 87.8, 86.2, 86.1, 82.2, 81.3, 72.4, 71.8, 68.9, 68.1, 61.3, 56.8, 56.0, 53.0.
T550 49407-49455 Sentence denotes HRMS (ESI+): m/z calcd for C29H34N12O9Cl [M+H]+:
T551 49456-49481 Sentence denotes 729.2255, Found 729.2256.
T552 49483-49675 Sentence denotes 4.1.39 (2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[(2-{[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxy}ethyl)[(4-chlorophenyl)methyl]amino]methyl}oxolane-3,4-diol (16)
T553 49676-49919 Sentence denotes Using method C with 36 (172 mg, 0.18 mmol, 1.00 eq) and a 0–40% linear gradient of acetonitrile in TEAAc buffer 50 mM, pH 7 for purification, 16 (45 mg, 37%) was obtained as a white powder with 98% purity determined by HPLC analysis at 260 nm.
T554 49920-50494 Sentence denotes 1H NMR (600 MHz, DMSO‑d 6) δ 8.36 (s, 1H), 8.25 (s, 1H), 8.13 (s, 1H), 8.11 (s, 1H), 7.34 (br. s, 2H), 7.25 (br. s, 2H), 7.23–7.17 (m, 2H), 7.17–7.11 (m, 2H), 6.00 (d, J = 6.2 Hz, 1H), 5.84 (d, J = 5.0 Hz, 1H), 5.45–5.39 (m, 2H), 5.27 (d, J = 4.8 Hz, 1H), 5.12 (d, J = 5.4 Hz, 1H), 4.58 (q, J = 5.5 Hz, 1H), 4.48 (dd, J = 6.2 Hz, J = 4.8 Hz, 1H), 4.30 (td, J = 4.6 Hz, J = 2.9 Hz, 1H), 4.04 (q, J = 5.1 Hz, 1H), 4.02–3.96 (m, 2H), 3.70–3.63 (m, 2H), 3.60–3.48 (m, 4H), 2.80 (dd, J = 14.0 Hz, J = 4.5 Hz, 1H), 2.67 (dd, J = 13.9 Hz, J = 7.0 Hz, 1H), 2.61 (q, J = 6.1 Hz, 2H).
T555 50495-50702 Sentence denotes 13C NMR (150 MHz, DMSO‑d 6) δ 156.2, 156.0, 152.6, 152.5, 149.3, 149.0, 139.8, 139.7, 138.2, 131.1, 130.4, 127.8, 119.3, 119.16, 87.67, 86.3, 86.1, 82.4, 81.2, 72.4, 71.8, 69.0, 67.5, 61.5, 57.5, 55.8, 52.9.
T556 50703-50751 Sentence denotes HRMS (ESI+): m/z calcd for C29H35N11O7Cl [M+H]+:
T557 50752-50777 Sentence denotes 684.2404, Found 684.2398.