The Journal of Organic Chemistry
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silica gel (2 cm thick), using the same mixture as eluent (25 mL). The
filtrate was concentrated. The crude residue was purified by flash
chromatography (CH2Cl2/MeOH 100:0 to 90:10) to afford pure 24
(m, 8H; H-2, H-5′ and H-6*), 3.80−3.50 (m, 34H; H-4, H-5, H-6, H-3′,
H-6′, H-2* and 3 × MeO), 3.50−3.38 (m, 10H; H-3*, H-4* and MeO),
3.26−3.10 (m, 6H; H-2′, H-4′ and H-1*a), 2.99 (m, 2H; H-7*a), 2.80
(m, 2H; H-7*b), 2.54−2.39 (m, 4H; H-1*b and H-5*), 1.86 (m, 4H;
H-14*), 1.58 (m, 4H; H-8*), 1.31 ppm (m, 20H; H-9* to H-13*); 13C
NMR (CD3OD, 100 MHz) δ 146.6, 145.8 (C-8′ and C-11), 125.3
(C-9′), 125.0 (C-12), 100.6 (C-1′), 84.8 (C-3′), 84.6 (C-1), 83.5 (C-2′),
81.6 (C-3), 80.0 (C-2), 79.9 (C-4′), 79.3, 79.2 (C-4 and C-3*), 77.2
(C-5), 72.3 (C-5′), 71.1 (C-4*), 70.6 (C-6′), 69.8 (C-2*), 67.6 (C-5*),
67.2 (C-10), 65.4 (C-7′), 62.5 (C-6), 61.4, 60.6, 59.1, 59.0 (4 × MeO),
58.1 (C-6*), 56.8 (C-1*), 54.0 (C-7*), 51.5 (C-15*), 31.3, 30.5, 30.4,
30.0, 28.3, 27.5, 25.0 ppm (C-8* to C-14*); IR (neat) 3356 cm−1
(broad, O-H); HRMS (ESI) m/z calcd for C74H127N14O28 [M + H]+
1659.8939; found 1659.8814. HRMS (ESI) m/z calcd for C74H128N14O28
[M + 2H]2+ 830.4506; found 830.4431.
(16.5 mg, 70%) as a colorless oil. Rf 0.30 (CH2Cl2/MeOH 95:5); [α]D20
=
+68.5 (c 0.5, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 7.86 (s, 2H; H-12),
7.81 (s, 2H; H-9′), 7.40−7.00 (m, 30H; ArH Bn), 7.20 (d, J = 8.6 Hz, 4H;
ArH PMB), 6.81 (d, J = 8.6 Hz, 4H; ArH PMB), 6.34 (d, J = 5.1 Hz, 2H;
H-1), 5.99 (d, J = 3.1 Hz, 2H; H-1*), 5.15 (d, J = 3.4 Hz, 2H; H-1′), 4.96
(d, J = 11.3 Hz, 2H; H-10a), 4.81 (dd, J = 3.1, 2.8 Hz, 2H; H-2*), 4.76−
4.37 (m, 22H; 3 × CH2 Bn, CH2 PMB, H-10b and H-7′), 4.04 (dd, J = 8.0,
2.8 Hz, 2H; H-3*), 3.96 (dd, J = 8.7, 8.0 Hz, 2H; H-4*), 3.89−3.47 (m,
24H; H-2, H-3, H-4, H-6, H-3′, H-5′, H-6′, H-5* and H-6*), 3.77 (s, 6H;
MeO), 3.70 (s, 6H; MeO), 3.58 (s, 6H; MeO), 3.51 (s, 6H; MeO),
3.42(m, 2H; H-5), 3.39 (s, 6H; MeO), 3.33 (t, J = 9.2 Hz, 2H; H-4′),
3.17 ppm (dd, J = 9.9, 3.4 Hz, 2H; H-2′); 13C NMR (CDCl3, 100 MHz) δ
159.3 (Ar), 145.6, 145.0 (C-11 and C-8′), 138.3, 138.2, 137.9, 130.2,
129.6, 129.0−127.5 (Ar), 123.5, 122.7 (C-12 and C-9′), 113.9 (Ar), 99.4
(C-1′), 85.2 (C-1*), 83.4 (C-3′), 83.0 (C-1), 82.3 (C-2′), 82.0 (C-3), 79.9
(C-2), 78.6 (C-3* and C-4′), 77.8 (C-4), 74.8 (C-5*), 74.5 (CH2 Bn/
PMB), 74.4 (C-5), 74.3 (C-4*), 74.0 (C-2*), 73.4, 73.1, 72.6 (CH2 Bn/
PMB), 71.0 (C-5′), 70.1 (C-6′), 68.5 (C-6*), 66.7 (C-10), 64.9 (C-7′),
61.5 (C-6), 61.3, 60.5, 59.1, 58.6, 55.4 (5 × MeO); IR (neat) 3468 cm−1
(broad, O-H); HRMS (ESI) m/z calcd for C114H142N12O32 [M + 2H]2+
1095.4921; found 1095.4842.
Cluster 28. To a solution of 19 (1 equiv, 25.1 mg, 0.016 mmol) and
2516b (10.5 equiv, 85.8 mg, 0.172 mmol) in DMF (4 mL) was added a
bright yellow suspension of CuSO4·5H2O (1 equiv, 4 mg, 0.016 mmol)
and sodium ascorbate (2 equiv, 6.5 mg, 0.033 mmol) in H2O (1 mL).
The mixture was heated at 80 °C for 1 h under microwave irradiation.
The mixture was evaporated under reduced pressure, diluted in a
mixture of MeCN/water/30 wt %-NH4OH (9:1:1), and filtered with the
same eluent on a small pad of SiO2 (typically 1 cm thick). The solvents
were evaporated under reduced pressure and the crude product was
purified by flash chromatography (CH2Cl2/MeOH 100:0 to 95:5)
to afford 28 (58.9 mg, 0.013 mmol, 79%) as a colorless oil. Rf 0.41
Cluster 26. To a solution of 22 (1 equiv, 8.3 mg, 0.00831 mmol) and
2516b (4 equiv, 15.7 mg, 0.0332 mmol) in DMF (1 mL) was added a
bright yellow solution of CuSO4·5H2O (0.25 equiv, 0.519 mg, 0.00208
mmol) and sodium ascorbate (0.5 equiv, 0.823 mg, 0.00415 mmol) in
H2O (0.2 mL). The mixture was stirred and heated under microwave
irradiation at 80 °C for 1 h. The mixture was diluted with a mixture of
CH3CN/EtOAc/30 wt %-NH4OH (2:2:1) and filtered through a pad of
silica gel (2 cm thick), using the same mixture as eluent (25 mL). The
filtrate was concentrated. The crude residue was purified by flash
chromatography (CH2Cl2/MeOH 100:0 to 90:10) to afford pure 26
(CH2Cl2/MeOH 95:5); [α]2D0 = +58.1° (c = 1, CH2Cl2); H NMR
1
(CDCl3, 400 MHz) δ7.88 (s, 1H), 7.78 (s, 1H), 7.61 (s, 2H), 7.60 (s,
1H), 7.56 (m, 3H) (H-12′, H-12‴, H-9′, H-9″, H-9‴, H-X9, H-Y9,
H-Y12), 6.18 (d, J = 5.6 Hz, 1H; H-1″ or H-X1), 6.16 (d, J = 5.6 Hz, 1H;
H-1″ or H-X1), 5.53 (d, J = 3.4 Hz, 1H; H-1‴ or H-Y1),), 5.50 (d, J = 3.6
Hz, 1H; H-1‴ or H-Y1), 5.36 (s, 1H; H-1), 5.12 (d, J = 3.6 Hz,
1H; H-1′), 5.08−4.97(m, 12H, H-Z3 and H-Z4), 4.97−4.89 (m, 8H, H-
10′a, H-10‴a and H-Z2), 4.74−4.43 (m, 15H, H-5, H-7′, H-7″, H-7‴,
H-X7, H-Y7, H-10′b, H-10‴b and H-Y10), 4.33−4.22 (m, 14H, H-3″,
H-X3 and H-Z15), 4.16−4.08 (m, 12H, H-Z6), 3.99−3.88 (m,
4H, H-4″, H-X4, H-5″, H-X5), 3.36 (m, 60H,H-2″, H-X2, H-3′,
H-3‴, H-Y3, H-4, H-4′, H-4‴, H-Y4, H-5′, H-5‴, H-Y5, H-6, H-6′, H-
6″, H-6‴, H-X6, H-Y6 and 12 MeO), 3.34 (t, J = 3.3 Hz, 1H, H-3), 3.22
(dd, J = 9.5 and 3.3 Hz, 1H, H-2′), 3.20−3.12 (m, 8H, H-2‴, H-Y2 and
H-Z1), 3.03 (d, J = 3.3 Hz, 1H; H-2), 2.74−2.64 (m, 6H, H-Z7a), 2.64−
2.58 (m, 6H, H-Z5), 2.58−2.48 (m, 6H, H-Z7b), 2.3 (t, 6H, J = 11.1 Hz,
H-Z1b), 2.04 (s, 18H, OAc), 1.99 (s, 36H, OAc), 1.98 (s, 18H, OAc),
1.90−1.80 (m, 12H, H-Z14), 1.46−1.13 (m, 72H, from H-Z8 to H-Z13)
ppm; 13C NMR (CDCl3, 100 MHz, 70000 scans) δ 171.0, 170.4, 170.1,
169.8 (CO acetate), 145.3, 145.1, 144.77, 144.73, 144.67, 144.64,
144.55, 144.4 (C-8′, C-8″, C-8‴, C-X8, C-Y8, C-11′, C-11‴ and C-Y11),
124.9, 124.6, 124.5, 122.9, 122.6 (C-9′, C-9″, C-9‴, C-X9, C-Y9, C-12′,
C-12‴ and C-Y12), 100.5 (C-1), 97.0 (C-1′), 96.7, 96.6, (C-1‴ and
C-Y1), 83.2, 83.02, 82.92, 82.88, 82.77 (C-1″, C-X1, C-3′, C-3″, C-3‴,
C-X3 and C-Y3), 82.0 (C-2‴ and C-Y2), 81.6 (C-2′), 81.3, 81.2 (C-2″
and C-X2), 80.6 (C-2), 79.4 (C-3), 77.96, 77.87, 77.78, 77.70 (C-4, C-4′,
C-4‴, C-Y4), 75.6 (C-5), 74.8 (C-Z3), 73.3, 73.2, 73.1, 72.9 (C-4″,
C-X4, C-5″ and C-X5), 70.8, 70.7, 70.5 (C-5′, C-5‴ and C-Y5), 69.6
(C-Z4), 69.5 (C-Z2), 69.0, 68.8, 68.7, 68.6 (C-6′, C-6″, C-6‴, C-X6 and
C-Y6), 66.5 (C-6), 66.2 (C-10′), 66.1 (C-10‴), 65.2, 64.9 (C-7′, C-7″,
C-7‴, C-X7, C-Y7, and C-Y10), 61.5 (C-Z5), 61.03, 60.99, 60.96, 60.33,
60.29 (OMe), 59.6 (C-Z6), 59.44, 59.41, 59.22, 59.18, 58.5, 58.2, 57.6
(OMe), 53.5 (C-Z1), 51.9 (C-Z7), 50.4 (C-Z15), 30.52−30.31
(C-Z14), 29.0, 27.2, 26.6 (from C-Z9 to Z-13), 24.7 (C-Z8), 20.96,
20.93, 20.83, 20.77 (CH3-CO), ppm; IR (neat): 1744 (strong
CO) cm−1 ; MS (ESI) m/z calcd for C210 H333 N30 O78 [M + 3H]3+
1507.7666; found 1507.7685.
(12.1 mg, 73%) as a colorless oil. Rf 0.30 (CH2Cl2/MeOH 95:5); [α]D20
=
1
+57.7 (c 0.5, CHCl3); H NMR (CDCl3, 400 MHz) δ 7.87 (s, 2H;
H-12), 7.55 (s, 2H; H-9′), 6.41 (d, J = 3.8 Hz, 2H; H-1), 5.13 (d, J =
3.3 Hz, 2H; H-1′), 5.07 (t, J = 8.9 Hz, 2H; H-4*), 5.03 (dd, J = 9.2,
8.9 Hz, 2H; H-3*), 4.98 (d, J = 11.6 Hz, 2H; H-10a), 4.96 (ddd, J = 10.2,
9.2, 5.3 Hz, 2H; H-2*), 4.67 (d, J = 11.6 Hz, 2H; H-10b), 4.66 (d, J =
12.4 Hz, 2H; H-7′a), 4.59 (d, J = 12.4 Hz, 2H; H-7′b), 4.29 (t, J = 7.3 Hz,
4H; H-15*), 4.15 (d, J = 2.2 Hz, 4H; H-6*), 3.90−3.62 (m, 16H; H-2,
H-3, H-4, H-6, H-5′ and H-6′), 3.69 (s, 6H; MeO), 3.59 (s, 6H; MeO),
3.58 (m, 4H; H-3′ and H-5), 3.51 (s, 6H; MeO), 3.41 (s, 6H; MeO),
3.35 (t, J = 9.4 Hz, 2H; H-4′), 3.18 (dd, J = 11.3, 5.3 Hz, 2H; H-1*a),
3.17 (dd, J = 9.8, 3.3 Hz, 2H; H-2′), 2.71 (m, 2H; H-7*a), 2.63 (dt, J =
8.9, 2.2 Hz, 2H; H-5*), 2.55 (m, 2H; H-7*b), 2.32 (dd, J = 11.3, 10.2 Hz,
2H; H-1*b), 2.10−1.97 (several s, 24H; Ac), 1.85 (m, 4H; H-14*),
1.48−1.20 ppm (m, 24H; H-8* to H-13*); 13C NMR (CDCl3,
100 MHz) δ 171.1, 170.5, 170.2, 169.9 (CO acetate), 145.68, 145.67
(C-8′ and C-11), 123.4 (C-12), 122.7 (C-9′), 99.4 (C-1′), 83.4 (C-3′),
83.0 (C-1), 82.3 (C-2′), 81.4 (C-3), 79.5 (C-2), 78.6 (C-4′), 77.8 (C-4),
75.0 (C-5), 74.9 (C-3*), 71.0 (C-5′), 69.8 (C-6′), 69.7, 69.6 (C-2* and
C-4*), 66.7 (C-10), 64.9 (C-7′), 61.8 (C-6), 61.6 (C-5*), 61.2 (MeO),
60.3 (MeO), 59.7 (C-6*), 59.0 (MeO), 58.7 (MeO), 53.1 (C-1*), 51.9
(C-7*), 50.5 (C-15*), 30.3, 29.5, 29.1, 27.4, 27.3, 26.6, 24.8 (C-8* to
C-14*), 21.1−20.6 ppm (CH3 acetate); IR (neat) 3467 (broad, O-H),
1746 cm−1 (strong, CO acetate); HRMS (ESI) m/z calcd for
C90H142N14O36Na [M + Na]+ 2017.9603; found 2017.9490.
Cluster 27. To a solution of 22 (1 equiv, 12.1 mg, 0.00606 mmol) in
a mixture of MeOH/water (1:1 4 mL) was added Amberlite IRA-400
(OH−) (300 mg) at room temperature. The mixture was stirred at 40 °C
for 16 h. The mixture was filtered (rinsing with MeOH, water and
mixture thereof). The filtrate was concentrated to afford pure 27
(9.0 mg, 89%) as a colorless viscous oil. [α]2D0 = +61.3 (c 0.5, MeOH);
1H NMR (CD3OD, 400 MHz) δ 8.11 (s, 2H; H-12), 7.98 (s, 2H; H-9′),
6.44 (d, J = 4.8 Hz, 2H; H-1), 5.16 (d, J = 3.3 Hz, 2H; H-1′), 5.00 (d, J =
11.4 Hz, 2H; H-10a), 4.67 (d, J = 12.4 Hz, 2H; H-7′a), 4.61 (d, J =
11.4 Hz, 2H; H-10b), 4.58 (d, J = 12.4 Hz, 2H; H-7′b), 4.35 (t, J =
7.0 Hz, 4H; H-15*), 4.00 (dd, J = 7.1, 5.1 Hz, 2H; H-3), 3.97−3.80
ASSOCIATED CONTENT
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J. Org. Chem. XXXX, XXX, XXX−XXX