10.1002/ejoc.201801320
European Journal of Organic Chemistry
FULL PAPER
167.8 (CH3OCO). HRMS (ESI/Q-TOF) m/z: [M
+
Na]+ calcd for
was recovered by centrifugation. The solid was sequentially washed with
C
27H34N4O14SNa 693.1664; found: 693.1684.
0.16 M EDTA, H2O and acetone to give 5 (0.458 g, 94%) as a white solid.
25
m.p. 259 ºC (recryst from DMSO-acetone); [α D
]
= +67.2 (c = 0.4 in
DMSO); 1H NMR (500 MHz, [D6]DMSO, 25 °C, TMS): δ = 2.43 (s, 3 H;
CH3Ph), 3.69 (s, 3 H; CH3O), 3.70 (s, 1 H; H-4’’), 3.80 (s, 2 H; H-4, H-4’),
3.96 (m, 3J (H-5’’,H-6’’a) = 4.9 Hz, 3J (H-5’’,H-6’’b) = 8.6 Hz, 1 H; H-5’’),
4.05 (s, 1 H; H-3’’), 4.18-4.21 (m, 3J (H-5,H-6a) = 4.6 Hz, 3J (H-5,H-6b) =
Compound 13a. To a solution of compound 4 (0.300 g, 0.45 mmol) in
anhydrous DMF (0.76 ml), NaN3 (0.03 g, 0.46 mmol) was added. The
mixture was stirred under N2 at 60 °C overnight. After concentration,
compound 13a (0.136 g, 56%) was obtained as a white crystalline solid
10.0 Hz, 3 H; H-5, H-5’, H-2’), 4.25-4.42 (m, 3J (H-5’’,H-6’’a) = 4.8 Hz, 3
J
by column chromatography (80:20 EtOAc-MeOH). m.p. 209-210 °C
25
(decomp) (recryst from H20); [α D
]
= +56.4 (c = 0.5 in DMSO); 1H NMR
(H-6’’a,H-6’’b) = 11.3 Hz, 8 H; H-2’, H-3, H-3’, H-6’’a, H-9, H-9’), 4.54 (m,
1H, 3J (H-5’’,H-6’’b) = 8.8 Hz, 3J (H-6’a,H-6’b) = 11.3 Hz, 1 H; H-6’’b),
4.60-4.64 (m, 3J (H-5,H-6a) = 3J (H-5’,H-6’a) = 4.6 Hz, 3J (H-6a,H-6b) =
3J (H-6’a,H-6’b) = 14.4 Hz, 3 H; H-2, H-6a, H-6’a), 4.72-4.82 (m, 7 H;
OCH2O), 5.07-5.11 (m, 7 H; H-6b, H-6’b, OCH2O), 7.49 (d, 3J (H,H) = 8.1
Hz, 2 H; H-aromatic), 7.81 (s, 1 H; H-7’), 7.83 (s, 1 H; H-7), 7.83 (d, 3J
(H,H) = 8.1 Hz, 2 H; H-aromatic), 8.17 (t, 3J (H-9’a,NH’) = 3J (H-9’b,NH’) =
6.0 Hz, 1 H; NH’), 8.19 (t, 3J (H-9a,NH) = 3J (H-9b,NH) = 6.0 Hz, 1 H;
NH); 13C NMR (125.7 MHz, [D6]DMSO, 25 °C, TMS): δ = 21.1 (CH3-Ph),
34.1 (C-9, C-9’), 46.1 (C-6, C-6’), 51.9 (OCH3), 66.2 (C-6’’), 67.2, 67.4
(C-3, C-3’), 67.5 (C-3’’), 69.1 (C-4’’), 69.3; 69.8 (C-4, C-4’), 73.1 (C-5’’),
74.4 (C-5, C-5’), 75.5 (C-2), 76.7 (C-2’’), 76.8 (C-2’), 86.7 87.2; 91.7
(OCH2O), 123.3 (C-7, C-7’), 127.8; 130.2; 132.1 (C-aromatic); 144.19 (C-
8, C-8’), 145.2 (C-aromatic), 167.0, 167.1 (CONH); 167.8 (CO2CH3).
HRMS (ESI/Q-TOF) m/z: [M + H]+ calcd for C38H49N8O19S 953.2829;
found: 953.2848; [M + Na]+ calcd for C38H48N8O19SNa 975.2649; found:
975.2669.
(500 MHz, [D6]DMSO, 25 °C, TMS): δ = 3.41 (dd, 3J (H-5’,H-6’a) = 4.8 Hz,
3J (H-6’a,H-6’b) = 13.2 Hz, 1H; H-6’a), 3.69 (s, 4 H; H-4’, CH3O), 3.80 (s,
1 H; H-4), 3.95 (dd, 1H, 3J (H-5’,H-6’a) = 4.8 Hz, 3J (H-5’,H-6’b) = 9.7 Hz,
1 H; H-5’), 4.09 (dd, 1H, 3J (H-5’,H-6’a) = 9.7 Hz, 3J (H-6’a,H-6’b) = 13.2
Hz, 1 H; H-6’b), 4.14 (s, 1H; H-3’), 4.19 (dd, 3J (H-5,H-6a) = 4.7 Hz, 3J (H-
5,H-6b) = 10.4 Hz, 1 H; H-5), 4.28-4.32 (m, 3J (H-2’,H-3’) = 1.2 Hz, 3J (H-
7a,NH) = 5.9 Hz , 3 H; H-2’, H-3, H-9a), 4.38 (dd, 1H, 3J (H-9b,NH) = 6.0
Hz, 3J (H-9a,H-9b) = 15.1 Hz, 1 H; H-9b), 4.60-4.64 (m, 3J (H-5,H-6a) =
4.6 Hz, 3J (H-6a,H-6b) = 10.4 Hz, 2 H; H-2, H-6a), 4.77 (d, 3J (H,H) = 6.5
Hz, 1 H; OCH2O), 4.80 (d, 3J (H,H) = 6.5 Hz, 1 H; OCH2O), 4.84 (d, 3J
(H,H) = 6.5 Hz, 1 H; OCH2O), 4.80 (d, 1H, 3J (H,H) = 6.5 Hz, 1 H;
OCH2O); 5.00 (d, 3J (H,H) = 6.5 Hz, 1 H; OCH2O); 5.05-5.11 (m, 4 H; H-
6b, OCH2O), 7.82 (s, 1 H; H-7), 8.19 (t, 3J (H-9a,NH) = 3J (H-9b,NH) =
6.0 Hz, 1 H; NH); 13C NMR (125.7 MHz, [D6]DMSO, 25 °C, TMS): δ =
34.1 (C-9), 46.1 (C-6), 46.6 (C-6’), 51.9 (OCH3), 67.4 (C-3’), 67.5 (C-3),
69.3 (C-4), 70.1 (C-4’), 74.4 (C-5), 74.6 (C-5’), 75.5 (C-2), 76.8 (C-2´),
86.2, 86.4, 91.3 (OCH2O), 123.3 (C-7), 145.0 (C-8), 167.1 (HNCO), 167.8
(CH3OCO). HRMS (ESI/Q-TOF) m/z: [M + Na]+ calcd for C20H27N7O11Na
564.1649; found: 564.1661. The byproduct 13b was isolated as a white
Compound 14. To a solution of compound 5 (0.30 g, 0.32 mmol) in
anhydrous DMSO (4.3 mL) was added NaN3 (0.04 g, 0.64 mmol). The
reaction mixture was stirred under Ar atmosphere at 100 °C for 24 h.
Compound 14 precipitated from the reaction mixture upon addition of
acetone and it was recovered by centrifugation. The solid was
sequentially washed with acetone-H2O (90:10) and acetone. Compound
solid, from further fractions of the column (90:10 EtOAc-MeOH).
25
Compound 13b (0.05 g, 22%); m.p. 189-190 °C (recryst from H20). [α D
]
= +12.2 (c = 0.5 in DMSO). 1H NMR (500 MHz, [D6]DMSO, 25 °C, TMS):
δ = 3.42 (dd, 3J (H-5’,H-6’a) = 5.0 Hz, 3J (H-6’a,H-6’b) = 13.3 Hz, 1 H; H-
6’a), 3.69 (s, 1 H; H-4’), 3.73 (s, 3 H; CH3O), 3.81 (m, 3J (H-5,H-6b) = 3.0
Hz, 3J (H-4,H-5) = 7.3 Hz, 3J (H-5,H-6a) = 3J (H-5,OH) = 6.4 Hz, 1 H; H-5),
3.95 (m, 3J (H-5’,H-6’b) = 5.0 Hz, 3J (H-5’,H-6’b) = 9.9 Hz, 1 H; H-5’), 4.09
(dd, 1H, 3J (H-5’,H-6’a) = 9.9 Hz, 3J (H-6’a,H-6’b) = 13.2 Hz, 1 H; H-6’b),
4.15 (s, 1 H; H-3’), 4.27 (dd, 3J (H-3,H-4) = 2.2 Hz, 3J (H-4,H-5) = 7.3 Hz,
1 H; H-4), 4.30 (d, 1H, 3J (H-2’,H-3’) = 1.7 Hz, 1 H; H-2’), 4.32-4.37 (m, 3
H; H-6a, H-9), 4.51 (dd, 3J (H-5,H-6b) = 3.0 Hz, 3J (H-6a,H-6b) = 14.1 Hz,
1 H; H-6b), 4.81 (d, 3J (H,H) = = 6.4 Hz, 1 H; OCH2O), 4.83 (d, 3J (H,H) =
6.5 Hz, 1 H; OCH2O), 5.00 (d, 3J (H-,H-) = 6.5 Hz, 1 H; OCH2O), 5.06 (d,
3J (H,H) = 5.8 Hz, 1 H; OCH2O), 5.11 (d, 3J (H,H) = 6.4 Hz, 1 H; OCH2O),
5.27 (d, 3J (H,H) = 5.8 Hz, 1 H; OCH2O), 5.79 (s, 3J (H-5,OH) = 6.4, 1 H;
OH), 6.26 (d, 3J (H-3,H-4) = 2.2 Hz, 1 H; H-3), 7.76 (2, 1 H; H-7), 8.17 (t,
3J (H-9a,NH) = 3J (H-9b,NH) = 6.1 Hz, 1 H; NH); 13C NMR (125.7 MHz,
[D6]DMSO, 25 °C, TMS): δ = 34.2 (C-9), 46.6 (C-6’), 52.1, 51.2 (C-6,
OCH3), 67.4 (C-3’), 70.1 (C-4’), 70.9 (C-5), 73.5 (C-4), 74.6 (C-5’), 76.8
(C-2´), 86.4, 89.6, 91.3 (OCH2O), 112.8 (C-3), 123.8 (C-7), 143.4 (C-2),
144.8 (C-8), 161.3 (CH3OCO), 167.2 (HNCO). HRMS (ESI/Q-TOF) m/z:
[M + Na]+ calcd for C19H25N7O10Na: 534.1534; found: 534.1555.
14 (0.21 g, 80%). m.p. 229 ºC (recryst from DMSO-acetone); [α]D
25 +67.0
(c = 0.6; DMSO); 1H NMR (500 MHz, [D6]DMSO, 25 °C, TMS): δ = 3.42
(dd, 3J (H-5’’,H-6’’a) = 4.9 Hz, 3J (H-6’’a,H-6’’b) = 13.3 Hz, 1 H; H-6’’a),
3.69 (s, 1 H; CH3O), 3.71 (s, 1 H; H-4’’), 3.80 (s, 2 H; H-4, H-4’), 3.95 (dd,
3J (H-5’’,H-6’’a) = 4.9 Hz, 3J (H-5’’,H-6’’b) = 9.8 Hz, 1 H; H-5’’), 4.09 (dd,
3J (H-5’’,H-6’’a) = 9.8 Hz, 3J (H-6’’a,H-6’’b) = 13.3 Hz, 1 H; H-6’’b), 4.15 (s,
1 H; H-3’’), 4.19 (m, 2 H; H-5, H-5’), 4.29 (d, 3J (H-2’’,H-3’’) = 1.68 Hz, 1
H; H-2’’), 4.30 (s, 2 H; H-3, H-3’), 4.32 (d, 3J (H-2’,H-3’) = 1.43 Hz, 1 H; H-
2’), 4.28-4.40 (m, 4 H; H-9, H-9’), 4.62-4.64 (m, 3 H; H-2, H-6a, H-6’a),
4.76-4.85 (m, 6 H; OCH2O), 5.00 (d, 3J (H,H) = 6.6 Hz, 1 H; OCH2O),
5.06-5.12 (m, 7 H; H-6b, H-6’b, OCH2O), 7.82, 7.83 (2s, 2 H; H-7, H-7’),
8.19 (m, 2 H; NH, NH’); 13C NMR (125.7 MHz, [D6]DMSO, 25 °C, TMS): δ
= 34.1 (C-9, C-9’), 46.1 (C-6, C-6’), 46.6 (C-6’’), 51.9 (OCH3), 67.2, 67.3
(C-3, C-3’), 67.4 (C-3’’), 69.3, 69.8 (C-4, C-4’), 70.1 (C-4’’), 74.4, 74.5 (C-
5, C-5’), 74.6 (C-5’’), 75.5 (C-2), 76.8 (C-2, C-2’), 86.2, 86.4, 91.3,
(OCH2O), 123.3 (C-7, C-7’), 145.0 (C-8, C-8’), 167.1 (CONH, CONH’),
167.8 (CO2CH3). HRMS (ESI/Q-TOF) m/z [M
+
Na]+ calcd for
C31H41N11O16Na 846.2630; found: 846.2652.
Microwave-assisted synthesis of 13a. To a solution of compound 4
(0.300 g, 0.45 mmol) in anhydrous DMF (0.76 ml), NaN3 (0.03 g, 0.46
mmol) was added. The mixture was stirred under N2 and subjected to Mw
irradiation at 80 °C for 5 h, until complete consumption of the starting 4.
After concentration, the residue was subjected to column
chromatography (80:20 EtOAc-MeOH) to give compound 13a (0.19 g,
81%) as a white crystalline solid, which showed identical physical and
spectroscopic properties as the compound described above.
Microwave-assisted synthesis of 14. To a solution of compound 5
(0.11 g, 0.11 mmol) in dry DMSO (1.5 mL) was added NaN3 (0.02 g, 0.25
mmol). The mixture was heated under Mw irradiation at 100 °C for 1 h
(Ar atmosphere). Compound 5 (0.07 g, 70%) was isolated by the same
procedure described for 13a.
Compound 6. To a solution of compounds 12 (0.15 g, 0.19 mmol) and
14 (0.08 g, 0.19 mmol) in anhydrous DMSO (5 mL) CuOAc (0.001 g, 0.01
mmol) was added. The mixture was heated under Mw irradiation at
Compound 5. To a solution of compounds 12 (0.21 g, 0.51 mmol) and
13a (0.28 g, 0.51 mmol) in DMF (5 mL) was added CuOAc (0.003 g,
0.024 mmol). The mixture was heated under Mw irradiation at 100 °C for
30 min (Ar atmosphere). Compound 5 precipitated from the mixture and it
100°C for 30 min (Ar atmosphere). Upon cooling, compound 6
precipitated off and it was recovered by centrifugation. The solid was
sequentially washed with 0.16 M EDTA, H2O and acetone to give
compound 6 (0.17 g, 78%) as a white solid. m.p. 250 ºC (decomp)
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