Summary and Future Prospects
Scheme 3. Synthesis of propargyl-ADPr 19 (‘click’-ADPr)
2. The reaction mixture was stirred for 3 hours at room temperature after which it
7
was diluted with EtOAc and H2O. The organic layer was washed with H2O (3x), dried
(MgSO4) and concentrated under reduced pressure. Column chromatography (PetEt/
EtOAc, 100/0 – 85/15) yielded the title compound as a yellow oil. (1.20 g, 1.45 mmol, 73%). 1H-NMR (400 MHz, CDCl 3) δ: 7.37 – 7.27 (m, 10H, arom.), 5.84 (ddd, J = 22.2, 10.7, 5.6 Hz, 1H, CH2CHCH2), 5.62 (d, J = 8.1 Hz, 1H, NH), 5.29 – 4.88 (m, 9H, CHCH2, H2’, CH2 Bn, CH2 Cbz, NH, H1’), 4.57 (dd, J = 6.6, 5.0 Hz, 1H, H3’), 4.38 (dd, J = 12.5, 7.4 Hz, 1H, CH α-Lys), 4.18 – 4.08 (m, 1H, OCH2CH), 3.93 (dddd, J = 36.4, 18.8, 11.1, 5.3 Hz, 4H, H4’, H5’, OCH2CH), 3.16 – 2.94 (m, 2H, CH2 ε-Lys), 1.89 – 1.55 (m, 2H, CH2
β-Lys), 1.55 – 1.15 (m, 4H, CH2 δ-Lys, CH2 γ-Lys), 1.01 (ddt, J = 21.5, 12.2, 5.9 Hz, 28H,
CH, CH3, TIPDS). 13C-NMR (400 MHz, CDCl3) δ: 172.23 (CO, ε-Lys), 155.97, 155.41
(CO, OBn, Cbz), 136.23, 135.28 (Cq. arom.), 133.80 (CH2CHCH2), 128.55 - 128.00
(arom.), 117.21 (CHCH2), 103.58 (C1’), 81.86 (C4’), 76.94 (C2’), 73.38 (C3’), 67.92
(C5’), 67.01, 66.86 (CH2 OBn, CH2 Cbz), 65.10 (OCH2CH), 53.70 (CH, α-Lys), 40.57
(CH2, ε-Lys), 32.04 (CH2 β-Lys), 29.26 (CH2 δ-Lys), 22.28 (γ-Lys), 17.46, 12.67 (CH, CH3,
TIPDS). IR: 2944.8, 2867.9, 2361.5, 2342.3, 1717.8, 1457.8, 1246.4, 1035.7, 668.1. HRMS [C42H64N2O11Si2 + H]+: 829.4121 found, 829.4082 calculated.
2-O-[Nω-carbonyl-(Nα-benzyloxycarbonyl lysine
benzyl ester)]-3,5-O-(tetraisopropyldisiloxane-1,3-
diyl)-ᴅ-ribose (4)
Compound 3 (1.12 g, 1.35 mmol) was coevaporated with 1,4-dioxane (2x) and DCE (2x), dissolved in dry THF (15 ml) and Ir(COD)(PPhMe)2PF6 (0.12 g, 0.15 mmol) was added. H2 (g) was bubbled through
the reaction for a few seconds and the reaction was stirred at room temperature until TLC analysis indicated full conversion of the starting material. Sat. aq. NaHCO3 (5
ml) and I2 (0.45 g, 1.76 mmol) were added to the reaction mixture and stirred for
1 hour. The mixture was diluted with EtOAc and sat. aq. NaS2O3. The organic layer
washed with sat. aq. NaS2O3, brine (3x), dried (MgSO4) and concentrated in vacuo.
Column chromatography (PetEt/EtOAc, 100/0 – 50/50) yielded the title compound as a yellow oil (0.631 g, 0.80 mmol, 59%). 1H-NMR (400 MHz, CDCl
3) δ: 7.41 – 7.27 (m,
10H, arom.), 5.52 (t, J = 7.7 Hz, 1H, NH), 5.47 (d, J = 8.1 Hz, 1H, NH), 5.24 (d, J = 13.5 Hz, 1H, NH), 5.22 – 5.01 (m, 7H, H1’, OH, CH2 OBn, CH2 Cbz, NH), 4.97 (t, J = 5.4 Hz, 1H,
NH), 4.58 (dd, J = 6.9, 4.6 Hz, 1H, H2’), 4.44 – 4.35 (m, 1H, CHα-Lys), 4.09 – 3.77 (m, 4H, H5’, H4’, H3’), 3.24 – 2.98 (m, 2H, CH2 ε-Lys), 1.89 – 1.56 (m, 2H, CH2 β-Lys), 1.54 –
1.16 (m, 4H, CH2 δ-Lys, CH2 γ-Lys), 1.14 – 0.94 (m, 28H, CH, CH3, TIPDS). 13C-NMR (400
MHz, CDCl3) δ: 172.37 (CO ε-Lys), 156.15, 155.27 (CO OBn, Cbz), 136.26, 135.32
(Cq. arom.), 128.72, 128.18 (arom.), 99.58, 95.79 (C1’), 81.70 (C4’), 77.17 (C2’), 72.44, 70.74 (C3’), 67.25, 67.12 (CH2 Bn, CH2 Cbz), 64.56, 62.14 (C5’), 53.82 (CH α-Lys), 40.73
(CH2 ε-Lys), 32.30 (CH2 β-Lys), 29.77, 29.30 (CH2 δ-Lys), 22.39, 22.31 (CH2 γ-Lys), 17.55
- 12.65 (CH, CH3, TIPDS). IR: 3334.0, 2944.3, 2867.7, 2360.1, 2342.0, 1717.9, 1457.5,
1245.9, 1027.8. HRMS [C39H60N2O11Si2 + H]+: 789.38084 found, 789.37692 calculated.
Nω-(2-O-(carbonyl-Nω-lysine)-3,5-O-
(tetraisopropyldisiloxane-1,3-diyl)-ᴅ-ribosyl)-Nα-
benzyloxycarbonyl lysine benzyl ester (6)
Compound 4 (0.20 g, 0.25 mmol) was dissolved in acetone (3 ml) and H2O (18 μl). Cs2CO3 (162 mg, 0.50 mmol) and
7
2,2,2-trifluoro-N-phenylacetimidoyl chloride (110 mg, 0.53 mmol) were added and the reaction was stirred overnight at room temperature. The reaction was diluted with acetone, filtered over Celite, and concentrated under reduced pressure. Column chromatography (PetEt/EtOAc/1% Et3N, 90/10 – 75/25) yielded a mixture of the title
compound and compound 5 as a yellow oil (0.122 g, 0.13 mmol, 51%). 1H-NMR (400
MHz, CDCl3) δ: 7.51 – 7.40 (m, 2H, H arom.), 7.32 (dd, J = 15.5, 6.9 Hz, 18H, H arom.), 7.01 (d, J = 7.3 Hz, 1H, compound 5), 6.55 (s, 1H, H compound 5), 5.56 (d, J = 8.4 Hz, 1H, NH), 5.45 (d, J = 5.2 Hz, 1H, H1’), 5.34 (d, J = 8.1 Hz, 1H, NH), 5.21 – 5.03 (m, 8H, CH2 OBn, CH2 Cbz), 4.72 (t, J = 5.1 Hz, 1H, H2’), 4.66 (s, 1H, H2’), 4.40 (dd, J = 12.7, 7.2 Hz, 2H, CHα-Lys), 4.24 (dd, J = 9.2, 5.1 Hz, 2H, H3’), 4.06 (t, J = 9.8 Hz, 1H, H5’), 3.98 (ddd, J = 10.2, 9.1, 4.0 Hz, 3H, H5’), 3.90 – 3.81 (m, 1H), 3.69 – 3.58 (m, 1H, H4’), 3.40 (d, J = 5.4 Hz, 1H, H4’), 3.25 (t, J = 7.2 Hz, 2H, CH2 ε-Lys), 3.02 (d, J = 14.3 Hz, 1H, CH2 ε-Lys), 1.70 (dtt, J = 22.6, 15.6, 10.5 Hz, 3H, CH2 β-Lys), 1.45
– 1.15 (m, 6H, CH2 γ-Lys, CH2 δ-Lys), 1.15 – 0.92 (m, 52H, CH, CH3, TIPDS). 13C-NMR
(400 MHz, CDCl3) δ: 172.25 (CO CH2 ε-Lys), 157.59, 155.98 (CO Bn, Cbz); 136.33 -
135.37 (Cq. arom.), 130.61, 128.25 (arom.), 113.55 (compound 5), 87.76 (C1’), 77.33 (C4’), 75.63, 75.15 (C2’), 71.39, 71.00 (C3’), 67.33, 67.16 (CH2 Bn, CH2 Cbz), 59.07
(C5’), 53.86 (Cα), 42.05 (CH2 ε-Lys), 32.30, 32.05 (CH2 β-Lys), 27.61 (CH2 δ-Lys), 22.39
(CH2 γ-Lys), 17.51, 12.67 (CH, CH3, TIPDS). IR: 2944.2, 2363.5, 2343.1, 1749.4, 1457.7,
1235.4, 1037.7. HRMS [C39H58N2O10Si2 + H]+: 771.37028 found, 771.36635 calculated.
HRMS (compound 5) [C47H64N3O11Si2 + H]+: 960.41042 found, 960.40650 calculated.
1-O-(pent-4-ene)-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-
α,β-ᴅ-ribofuranoside (7)
ᴅ-Ribose (15 g, 100 mmol) was dissolved in 4-penten-1-ol (100 mL) and vigorously stirred at room temperature. Next, 300 mg camphor sulfonic acid (300 mg, 1.3 mmol) was slowly added and the reaction was stirred at room temperature and TLC analysis (CHCl3/EtOAc/MeOH; 7:2:1) was used
to monitor the reaction. The reaction mixture was concentrated under reduced pressure after 3 days and co-evaporated with toluene and pyridine (3x). Pyridine (150 ml) was added, the mixture was cooled to 0 °C and 1,3-dichloro-1,1,3,3- tetraisopropyldisiloxane (28 ml, 87.5 mmol) was slowly added to the reaction mixture over a 1 hour period. The reaction was stirred for 1.5 hours after all the reagent was added after which it was carefully quenched by the addition of sat. aq. NaHCO3. The
reaction mixture was extracted with EtOAc (3x), the organic layers washed with H2O
(3x), dried (MgSO4) and concentrated in vacuo. Column chromatography (Pentane/
EtOAc, 95/5 – 90/10) yielded the title compound as a colorless oil (29.3 g, 63.6 mmol, 64%). 1H-NMR (500 MHz, CDCl 3) δ: 5.81 (dddt, J = 16.9, 13.3, 10.2, 6.8 Hz, 1H), 5.07 – 4.93 (m, 3H), 4.91 (s, 1H), 4.52 (t, J = 5.4 Hz, 1H), 4.19 (dd, J = 7.3, 4.2 Hz, 0.3H), 4.08 – 3.98 (m, 4H), 3.80 – 3.74 (m, 1.3H), 3.74 – 3.68 (m, 0.3H), 3.65 (dt, J = 9.5, 6.7 Hz, 1H), 3.49 (dt, J = 9.5, 6.4 Hz, 0.3H), 3.37 (dt, J = 9.6, 6.4 Hz, 1H), 3.01 (d, J = 9.6 Hz, 0.3H), 2.99 (s, 1H), 2.20 – 2.03 (m, 3H), 1.75 – 1.68 (m, 0.6H), 1.68 – 1.60 (m, 2H), 1.14 – 1.02 (m, 36H). 13C-NMR (126 MHz, CDCl 3) δ: 138.28, 138.13, 114.94, 114.86, 106.31, 101.55, 83.66, 82.64, 75.97, 75.15, 71.37, 71.16, 67.42, 67.18, 66.30, 64.33, 62.18, 30.43, 30.41, 29.01, 28.86, 17.67, 17.64, 17.54, 17.53, 17.49, 17.48, 17.41, 17.38, 17.30, 17.26, 17.24, 17.14, 17.11, 17.08, 16.97, 13.66, 13.51, 13.44, 13.42, 13.35, 13.24, 13.01, 12.97, 12.72, 12.70.
7
1-O-(pent-4-ene)-2-O-(ρ-nitrophenoxycarbonyl)-3,5-O-
(tetraisopropyldisiloxane-1,3-diyl)-β-ᴅ-ribofuranoside (8)
Compound 7 (4.6 g, 10.0 mmol) was coevaporated with toluene (2x) and dissolved in DCM (5 ml). The reaction mixture was stirred at 0 °C and DIPEA (2.60 ml, 15.0 mmol) and ρ-nitrophenyl chloroformate (2.0 g, 10.0 mmol) were added. The reaction was stirred for 1 hour allowing the reaction to slowly reach room temperature, quenched with H2O, extracted with DCM (3x), dried (MgSO4), and concentrated in vacuo. Column
chromatography (Pentane/Et2O, 100/0 – 90/10) yielded the title compound as a
colorless oil (5.35 g, 8.4mmol, 84%). 1H-NMR (500 MHz, CDCl
3) δ: 8.27 (d, J = 9.1 Hz, 2H), 7.37 (d, J = 9.1 Hz, 2H), 5.90 – 5.72 (m, 1H), 5.15 (d, J = 4.6 Hz, 1H), 5.07 – 4.93 (m, 3H), 4.66 (dd, J = 6.8, 4.7 Hz, 1H), 4.10 – 3.98 (m, 2H), 3.91 – 3.82 (m, 1H), 3.72 (ddd, J = 13.2, 11.4, 6.5 Hz, 1H), 3.41 (dt, J = 9.4, 6.4 Hz, 1H), 2.11 (dd, J = 13.8, 6.4 Hz, 2H), 1.71 – 1.58 (m, 2H), 1.18 – 0.99 (m, 28H). 13C-NMR (126 MHz, CDCl 3) δ: 155.84, 155.70, 152.07, 151.75, 145.54, 145.48, 138.03, 138.00, 125.44, 125.36, 121.87, 121.78, 115.08, 103.66, 100.32, 81.92, 81.46, 80.46, 76.28, 73.32, 69.48, 68.56, 67.46, 64.89, 60.78, 30.32, 30.23, 28.84, 28.78, 17.59, 17.51, 17.48, 17.45, 17.41, 17.25, 17.18, 17.14, 17.10, 17.08, 17.00, 13.57, 13.44, 13.32, 13.22, 12.94, 12.92, 12.86. 1-O-(pent-4-ene)-2-O-[Nω-carbonyl-(Nα-
fluorenylmethoxycarbonyl lysine benzyl ester)]-3,5-O-
(tetraisopropyldisiloxane-1,3-diyl)-β-ᴅ-ribofuranoside
(9)
Fmoc-Lys-OBn (0.9 g, 2.2 mmol) and compound 8 (2.5 g, 3.9 mmol)was coevaporated with 1,4-dioxane (2x) and dissolved in DMF (11 mL). DIPEA (0.7 mL, 4 mmol) was added and the reaction was stirred at room temperature for 2 hours. The reaction mixture was diluted with H2O, extracted with Et2O, dried
(MgSO4) and concentrated under reduced pressure. Column chromatography
(Pentane/EtOAc, 95/5 – 80/20) yielded the title compound as a yellow oil. (1.25 g, 1.32mmol, 60%). 1H-NMR (500 MHz, CDCl 3) δ: 7.79 (d, J = 7.4 Hz, 2H), 7.62 (d, J = 7.2 Hz, 2H), 7.46 – 7.30 (m, 9H), 5.82 (dq, J = 10.0, 6.6 Hz, 1H), 5.39 (d, J = 8.0 Hz, 1H), 5.21 (dd, J = 36.6, 12.2 Hz, 2H), 5.13 (d, J = 4.6 Hz, 1H), 5.01 (dd, J = 26.3, 13.6 Hz, 2H), 4.89 (s, 1H), 4.86 – 4.75 (m, 1H), 4.63 – 4.53 (m, 1H), 4.51 – 4.36 (m, 3H), 4.25 (t, J = 6.7 Hz, 1H), 4.10 – 4.00 (m, 1H), 4.00 – 3.93 (m, 1H), 3.91 – 3.78 (m, 1H), 3.67 (dd, J = 15.7, 6.6 Hz, 1H), 3.47 – 3.30 (m, 1H), 3.22 – 3.13 (m, 1H), 3.13 – 3.01 (m, 1H), 2.18 – 2.02 (m, 2H), 1.95 – 1.81 (m, 1H), 1.72 (s, 2H), 1.69 – 1.59 (m, 2H), 1.58 – 1.43 (m, 2H), 1.43 – 1.32 (m, 1H), 1.32 – 1.20 (m, 1H), 1.18 – 0.97 (m, 28H). 13C-NMR (126 MHz, CDCl 3) δ: 172.23, 155.92, 155.49, 143.90, 143.74, 141.32, 138.06, 135.26, 128.66, 128.59, 128.42, 127.71, 127.08, 125.10, 119.97, 114.80, 104.63, 81.82, 77.09, 73.46, 67.23, 67.14, 67.04, 65.25, 53.74, 47.18, 40.71, 32.32, 30.25, 29.43, 28.73, 22.32, 17.52, 17.42, 17.37, 17.13, 17.06, 17.00, 13.32, 13.23, 12.82, 12.78. 1-O-(pent-4-ene)-2-O-[Nω-carbonyl-(Nα-
fluorenylmethoxycarbonyl lysine benzyl ester)]-3-O-
acetyl-5-O-(triisopropylsilyl)-β-ᴅ-ribofuranoside (10)
Compound 9 (1.25 g, 1.3 mmol) was dissolved in dry THF (25 ml) and Et3N.3HF (0.6 mL, 3.6 mmol) was added. The reaction mixture was stirred
7
for 12 hours and carefully quenched with sat. aq. NaHCO3, extracted with EtOAc (3x),
dried (MgSO4), and concentrated in vacuo. Column chromatography (Pentane/EtOAc,
40/60 – 10/90) yielded the intermediate compound as a colorless oil (736 mg, 1.05 mmol, 81%). The intermediate diol compound was dissolved in pyridine (10 mL), triisopropylsilyl chloride (0.32 mL, 1.5 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. Acetic anhydride (2 mL) was added and the reaction was stirred for at room temperature for 4 hours. The reaction mixture was concentrated in vacuo, dissolved in DCM and extracted with aq. NaHCO3 (sat.). The
organic layer was dried over MgSO4, concentrated under reduced pressure and
purified by column chromatography (Pentane/EtOAc, 80/20 – 70/30) to yield the title compound as a colorless oil. (484 mg, 0.54 mmol, 54% (42% starting from compound
9)). 1H-NMR (500 MHz, MeOD-CDCl 3) δ: 7.79 (d, J = 7.6 Hz, 2H), 7.66 (d, J = 7.4 Hz, 2H), 7.43 – 7.24 (m, 9H), 5.79 (ddt, J = 16.8, 10.2, 6.7 Hz, 1H), 5.35 (t, J = 5.6 Hz, 1H), 5.17 (dd, J = 30.1, 12.4 Hz, 2H), 5.11 (d, J = 4.8 Hz, 1H), 5.04 – 4.91 (m, 3H), 4.55 (s, 1H), 4.38 (dd, J = 10.3, 7.1 Hz, 1H), 4.32 (dd, J = 10.3, 7.3 Hz, 1H), 4.27 – 4.18 (m, 2H), 4.14 (dd, J = 11.0, 5.1 Hz, 1H), 3.82 (qd, J = 10.6, 5.2 Hz, 2H), 3.70 (dd, J = 15.7, 6.6 Hz, 1H), 3.39 (dd, J = 15.7, 6.7 Hz, 1H), 3.15 – 3.01 (m, 2H), 2.08 (dd, J = 14.2, 7.0 Hz, 2H), 2.01 (s, 3H), 1.84 (td, J = 14.0, 9.2 Hz, 1H), 1.72 (dt, J = 15.1, 8.9 Hz, 1H), 1.62 (dt, J = 14.1, 6.8 Hz, 2H), 1.50 (qd, J = 13.5, 6.5 Hz, 2H), 1.45 – 1.34 (m, 2H), 1.14 – 1.01 (m, 21H). 13C-NMR (126 MHz, MeOD-CDCl 3) δ: 172.58, 170.25, 157.25, 156.17, 143.90, 143.74, 141.19, 137.82, 135.75, 128.20, 127.95, 127.87, 127.43, 126.82, 126.80, 124.92, 124.86, 119.57, 114.06, 105.36, 80.80, 74.95, 72.42, 67.17, 66.69, 66.55, 64.47, 54.17, 47.02, 40.08, 30.74, 29.99, 28.87, 28.54, 22.60, 19.49, 17.17, 11.76. HRMS [C50H68N2O11Si + Na]+: 923.4484 found, 923.4485 calculated.
1-O-propargyl-2,3-bis-O-(4-methoxybenzyl)-5-O-tert-
butyldiphenylsilyl-α,β-ᴅ-ribofuranoside (14)
The trifluoroacetimidate donor 13 (2.15 g, 2.75 mmol), described in chapter 2, and propargyl alcohol (160 µL, 2.75 mmol) were co-evaporated with 1,4-dioxane (3x) and dissolved in dry DCM (30 mL) along with freshly activated 3Å molecular sieves. The reaction mixture was stirred at room temperature for 1 hour under argon to remove traces of water. The reaction mixture was cooled to -78 °C, TMSOTf (10 μL, 55 μmol) was added and the reaction mixture was stirred at -78 °C for 30 minutes. The reaction was quenched by the addition of triethylamine, filtered, concentrated in vacuo and purified by silica gel chromatography (Pentane/ EtOAc, 90/10 – 85/15) to obtain the title compound with the two anomers separated (β-anomer: 419 mg, 0.63 mmol; α-anomer: 1.04 g, 1.57 mmol; α/β=71/29; 80%). β-anomer: 1H-NMR (500 MHz, CDCl
3) δ: 7.66 (d, J = 6.9 Hz, 4H, arom. TBDPS), 7.46 –
7.32 (m, 6H, arom. TBDPS), 7.29 (d, J = 8.5 Hz, 2H, arom. PMB), 7.18 (d, J = 8.5 Hz, 2H, arom. PMB), 6.87 (d, J = 8.6 Hz, 2H, arom. PMB), 6.81 (d, J = 8.6 Hz, 2H, arom. PMB), 5.22 (s, 1H, H1’ ), 4.58 (AB, J = 36.4, 11.7 Hz, 2H, CH2 PMB), 4.39 (AB, J = 43.3, 11.4
Hz, 2H, CH2 PMB), 4.24 (dt, J = 7.4, 3.8 Hz, 1H, H4’), 4.21 – 4.11 (m, 3H, H3’, CH2CCH),
3.89 (d, J = 4.5 Hz, 1H, H2’), 3.85 (AB, J = 11.3, 3.3 Hz, 1H, H5’), 3.80 (s, 3H, CH3 PMB),
3.78 (s, 3H, CH3 PMB), 3.69 (AB, J = 11.3, 4.1 Hz, 1H, H5’), 2.38 (t, J = 2.4 Hz, 1H,
CH2CCH), 1.03 (s, 9H, tBu TBDPS). 13C-NMR (126 MHz, CDCl3) δ 159.48, 159.38 (Cq.
Arom.), 135.73, 135.70 (arom.), 133.54, 133.52, 130.08, 129.98 (Cq. Arom.), 129.84, 129.80, 129.75, 129.52, 127.81, 127.80, 113.95, 113.87 (arom.), 103.17 (C1’), 82.39
7
(C4’), 79.45 (C2’), 79.32 (CH2CCH), 77.06 (C3’), 74.60 (CH2CCH), 72.18, 72.07 (CH2 PMB), 64.00 (C5’), 55.40, 55.37 (CH3 PMB), 54.26 (CH2CCH), 26.95 (tBu TBDPS), 19.40 (Cq. tBu TBDPS). α-anomer: 1H-NMR (500 MHz, CDCl 3) δ: 7.59 (d, J = 7.8 Hz, 2H, arom. TBDPS), 7.54 (d, J = 7.8 Hz, 2H, arom. TBDPS), 7.47 – 7.32 (m, 6H, arom. TBDPS), 7.29 (d, J = 8.5 Hz, 2H, arom. PMB), 7.23 (d, J = 9.0 Hz, 2H, arom. PMB), 6.85 (d, J = 8.5 Hz, 2H, arom. PMB), 6.81 (d, J = 8.5 Hz, 2H, arom. PMB), 5.31 (d, J = 4.3 Hz, 1H, H1’), 4.65 (AB, J = 12.2, 7.5 Hz, 2H, CH2 PMB), 4.57 (d, J = 12.0 Hz, 1H, CH2 PMB), 4.51 (d, J = 12.4 Hz, 1H, CH2 PMB), 4.39 (d, J = 2.3 Hz, 2H, CH2CCH), 4.17 – 4.09 (m, 1H, H4’), 3.96 (dd, J = 6.5, 2.7 Hz, 1H, H3’), 3.86 (dd, J = 6.5, 4.4 Hz, 1H, H2’), 3.78 (d, J = 2.3 Hz, 6H, CH3 PMB), 3.60 (AB, J = 11.2, 3.4 Hz, 1H, H5’), 3.50 (AB, J = 11.1, 3.1 Hz, 1H, H5’), 2.40 (t, J = 2.2 Hz, 1H, CH2CCH), 0.94 (s, 9H, tBu TBDPS). 13C-NMR (126 MHz, CDCl3) δ: 159.39, 159.23 (Cq. Arom.), 135.69, 135.62 (arom.), 133.28, 133.14, 130.52, 129.97 (Cq. Arom.), 129.84, 129.78, 129.71, 129.68, 127.79, 127.75, 113.89, 113.76 (arom.), 98.93 (C1’), 84.13 (C4’), 79.83 (CH2CCH), 77.70 (C2’), 74.85 (C3’), 74.23 (CH2CCH), 72.19, 71.97 (CH2 PMB), 64.11 (C5’), 55.31 (CH3 PMB), 54.22 (CH2CCH), 26.84 (tBuTBDPS), 19.26 (Cq. tBu TBDPS). HRMS [C40H46O7Si + Na]+: 689.2902 found, 689.2902
calculated.
1-O-propargyl-2,3-bis-O-(4-methoxybenzyl)-α-ᴅ-ribofuranoside
(15)
Compound 14 (660 mg, 1 mmol) was dissolved in DCM (20 mL) and