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to afford 11 as a colorless oil (0.17 g, 0.254 mmol, 29%). 1H NMR 2.4), 6.78–6.74 (m, 4.5H), 7.25–7.16 (m, 6H), 7.39–7.35 (m, 4.5H),
(500 MHz, CDCl3) d 0.11 (s, 6H), 0.91 (s, 9H), 2.47 (d, 1H, J ¼ 8.0), 7.42 (d, 2H, J ¼ 7.2), 7.51–7.48 (m, 2H); 13C NMR (151 MHz,
3.06 (s, 1H), 3.16–3.18 (m, 1H), 3.35–3.37 (m, 1H), 3.76 (s, 6H), CDCl3) d ꢀ4.53, ꢀ4.42, 2.01, 18.28, 20.12, 20.40, 24.67, 24.78,
4.11–4.21 (m, 3H), 4.49 (d, 1H, J ¼ 12.1), 4.79 (d, 1H, J ¼ 12.1), 25.92, 43.06, 43.13, 43.24, 43.32, 55.28, 55.31, 58.23, 58.34,
4.97 (d, 1H, J ¼ 1.75), 6.79 (dd, 4H, J ¼ 2.3 and 9.2), 7.17–7.21 58.46, 64.08, 64.77, 68.92, 69.23, 72.39, 72.56, 72.62, 73.46,
(m, 3H), 7.27 (t, 2H, J ¼ 7.4), 7.38 (d, 4H, J ¼ 9.2), 7.44 (d, 2H, J ¼ 75.76, 76.04, 76.74, 76.95, 77.37, 81.46, 81.57, 83.71, 83.91,
8.6), 7.50 (d, 2H, J ¼ 7.5); 13C NMR (126 MHz, CDCl3) d ꢀ4.5, 85.94, 86.02, 86.11, 106.77, 107.01, 113.10, 113.14, 113.19,
18.2, 25.8, 55.2, 64.7, 69.1, 72.3, 76.6, 76.8, 83.8, 86.0, 106.7, 117.50, 117.66, 121.32, 121.45, 126.79, 127.65, 127.67, 127.74,
113.1, 121.4, 126.7, 127.6, 127.8, 128.3, 130.1, 132.2, 136.2, 127.83, 127.86, 127.90, 128.40, 128.45, 128.52, 130.26, 132.22,
136.2, 138.5, 145.0, 158.4; HRMS (ESI-TOF) m/z calc. for C41
-
136.27, 136.39, 136.53, 138.87, 145.06, 145.13, 158.49; 31P NMR
H48O7SiNa [M + Na]+; 703.3067 found 703.3080.
(202 MHz, CDCl3) d 149.2, 149.9; HRMS (ESI-TOF) m/z calc. for
C
50H65N2O8PSiK [M + K]+; 919.3885 found 919.3879.
3-O-(tert-Butyldimethylsilyl)-1-O-(4-ethynylphenyl)methyl-5-O-
[bis(4-methoxyphenyl)phenylmethyl]-b-D-ribofuranose (12)
Synthesis of controlled pore glass support (15)
TEA (0.40 mL, 2.87 mmol) and TBDMS-Cl (2.0 g, 1.31 mmol) N,N-Dimethyl-4-aminopyridine (93 mg, 0.76 mmol) and suc-
were added to a solution of 10 (0.50 g, 0.876 mmol) in DMF (10 cinic anhydride (0.15 g, 1.52 mmol) were added to a solution of
mL) at room temperature. Aer being stirred at room temper- compound 12 (0.26 g, 0.38 mmol) in pyridine (3.0 mL). Aer
ature for 24 h, the mixture was partitioned between EtOAc and being stirred for 24 h at room temperature, the mixture was
H2O. The organic layer was washed with brine, dried over partitioned between EtOAc and H2O. The organic layer was
Na2SO4, and concentrated in vacuo. The crude material was washed with saturated NaHCO3 aqueous solution and brine,
puried by column chromatography (15–20% EtOAc in hexane) dried over Na2SO4, and concentrated in vacuo. The resulting
to afford 12 as a colorless oil (0.26 g, 0.38 mmol, 43%). 1H NMR residue was dissolved in DMF (4.1 mL). Aminopropyl controlled
(500 MHz, CDCl3) d ꢀ0.13 (s, 3H), ꢀ0.004 (s, 3H), 0.81 (s, 9H), pore glass (0.66 g, CPG) and 1-(3-(dimethylamino)propyl)-3-
2.76 (d, 1H, J ¼ 2.3), 3.06 (s, 1H), 3.07–3.09 (m, 1H), 3.37–3.40 ethylcarbodiimide hydrochloride (EDC$HCl, 78 mg, 0.41
(m, 1H), 3.76 (s, 6H), 3.94–3.98 (m, 1H), 4.12–4.15 (m, 1H), 4.40 mmol) were added to the solution of 14, and the mixture was
(t, 1H, J ¼ 5.7), 4.53 (d, 1H, J ¼ 12.0), 4.80 (d, 1H, J ¼ 12.1), 5.11 kept at room temperature for 3 days. Aer the resin was washed
(s, 1H), 6.79 (dd, 4H, J ¼ 5.8 and 8.6), 7.18–7.20 (m, 3H), 7.27 (t, with pyridine, 15 mL of capping solution (0.1 M DMAP in
2H, J ¼ 7.4), 7.38 (d, 4H, J ¼ 9.2), 7.42 (d, 2H, J ¼ 8.1), 7.50 (d, pyridine/Ac2O 9 : 1) was added to the resin and the mixture was
2H, J ¼ 7.5); 13C NMR (126 MHz, CDCl3) d ꢀ4.8, 17.9, 25.7, 55.2, kept at room temperature for 1 day. The resin was washed with
63.8, 69.2, 72.4, 75.5, 76.8, 83.0, 83.2, 85.9, 106.6, 113.1, 126.8, pyridine, EtOH, and CH3CN and dried under vacuum to give
127.8, 127.9, 128.3, 130.1, 132.2, 136.2, 136.2, 138.2, 145.5, solid support 15. The amount loaded nucleoside 14 to the solid
158.5; HRMS (ESI-TOF) m/z calc. for C41H48O7SiNa [M + Na]+; support was 44 mmol gꢀ1 from calculation of released dime-
703.3067 found 703.3071.
thoxytrityl cation by a solution of 70% HClO4 : EtOH (3 : 2, v/v).
2-O-(tert-Butyldimethylsilyl)-3-O-[(2-
Solid-phase peptide synthesis
cyanoethoxy)(diisopropylamino)phosphanyl-1-O-(4-
ethynylphenyl)methyl]-5-O-[bis(4-methoxyphenyl)
phenylmethyl]-b-D-ribofuranose (13)
The peptides were synthesized by solid-phase synthesis with the
9-uorenylmethyloxycarbonyl (Fmoc) chemistry in a 5.0 mmol
scale. A 4-methylbenzhydrylamine resin, which generates an
Chloro(2-cyanoethoxy)(N,N-diisopropylamino)phosphine (0.51 amide function at the C terminal, was used as the solid support
mL, 2.28 mmol) and N,N-diisopropylethylamine (1.0 mL, 5.70 for the peptide synthesis. Amino acids protected with the Fmoc
mmol) were added to a solution of 11 (0.78 g, 1.14 mmol) in THF group were reacted by using 1-[bis(dimethylamino)methylene]-
(8 mL) under argon atmosphere and the mixture was stirred for 1H-benzotriazolium 3-oxide hexauorophosphate (HBTU) as
1.5 h at room temperature. The mixture was partitioned a coupling reagent in the presence of 1-hydroxybenzotriazole
between saturated NaHCO3 solution and CHCl3. The organic (HOBt) and N,N0-diisopropylethylamine (DIPEA). The Fmoc
layer was washed with brine, dried over Na2SO4 and concen- group was deprotected by 25% piperidine in DMF and each
trated in vacuo. The crude material was puried by column coupling reaction was performed for 30 min. Cleavage of the
chromatography (25% EtOAc in hexane) to afford 13 as a color- peptide from the resin and deprotection of the side chain were
1
less oil (0.87 g, 0.99 mmol, 87%). H NMR (600 MHz, CDCl3) performed by treating with a TFA solution containing m-cresol
d 0.065 (s, 1H), 0.079 (d, 3H, J ¼ 4.2), 0.10 (d, 2H, J ¼ 3.0), 0.11 (s, (95/5, v/v) for 1 h. Diethyl ether (Et2O) was added to the solution.
0.5H), 0.89 (d, 9H, J ¼ 6.6), 0.91 (s, 2H), 0.96 (d, 2H, J ¼ 6.6), 1.09 The resulting precipitate was washed several times with Et2O to
(d, 3H, J ¼ 7.2), 1.12 (t, 6H, J ¼ 7.8), 2.31 (t, 1H, J ¼ 6.9), 2.57 (q, give the peptide. The peptides were successfully identied by
0.5H, J ¼ 7.0), 3.06 (d, 1H, J ¼ 3.6), 3.10–3.08 (m, 0.5H), 3.39 (dd, matrix-assisted laser desorption ionization time-of-ight mass
0.5H, J ¼ 10.2 and 1.8), 3.53–3.47 (m, 2H), 3.74 (s, 1.5H), 3.75 (d, spectrometry (MALDI-TOF/MS). Peptide 1 m/z ¼ 1511.97 (calcd
5.5H, J ¼ 2.4), 4.16 (d, 0.5H, J ¼ 3.6), 4.21–4.19 (m, 0.5H), 4.33– for C60H112N37O10 [M + H]+, 1511.86); peptide 2 m/z ¼ 1910.03
4.24 (m, 1.5H), 4.49 (d, 0.5H, J ¼ 3.6), 4.52 (d, 0.5H, J ¼ 13.2), (calcd for C74H133N44O17 [M + H]+, 1910.24); peptide 3 m/z ¼
4.82 (dd, 0.5H, J ¼ 12.6, 4.2), 4.95 (s, 0.5H), 4.97 (d, 0.5H, J ¼ 2007.92 (calcd for C81H147N44O17 [M + H]+, 2008.42).
34822 | RSC Adv., 2020, 10, 34815–34824
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