I. Paterson et al.
FULL PAPERS
(1H, d, J=10.4 Hz; H26a), 4.92 (1H, d, J=10.6 Hz; H15), 3.65–3.71
(2H, m; H7, H9), 3.35 (1H, t, J=5.4 Hz; H19), 3.14 (1H, ddd, J=6.7,
13.4, 18.0 Hz; H22), 3.04 (1H, dd, J=1.7, 7.7 Hz; H13), 2.62 (1H, ddd,
J=6.6, 13.7, 17.2 Hz; H14), 2.35–2.43 (1H, m; H6), 2.08–2.15 (1H, m;
H20), 2.05 (2H, d, J=6.8 Hz; H17a, H17b), 1.93 (12H, dt, J=7.0,
13.5 Hz; H18), 1.87 (1H, brs; H10a), 1.71 (2H, t, J=7.2 Hz; H10b,
H11a), 1.65 (3H, s; Me16), 1.49–1.55 (2H, m; H11b, H12), 1.40–1.45
(1H, m; H8a), 1.17–1.22 (1H, m; H8b), 1.14 (3H, d, J=6.8 Hz; Me20),
1.01 (3H, obsd, J=6.3 Hz; Me14), 1.00 (3H, obsd, J=6.9 Hz; Me6), 0.98
(3H, obsd, J=7.1 Hz; Me22), 0.93 (3H, obsd, J=6.8 Hz; Me12),
0.92 ppm (3H, obsd, J=6.4 Hz; Me18); 13C NMR (500 MHz, C6D6): d=
166.5 (C1), 145.0 (C5), 142.2 (C3), 34.4 (C23), 133.4 (C16), 132.6 (C25),
130.2 (C24), 129.9 (C15), 129.3 (C4), 118.7 (C2), 118.2 (C26), 81.0 (C13),
78.1 (C21), 75.3 (C19), 72.5 (C7), 70.0 (C9), 44.0 (C6), 40.7 (C12), 37.9
(C20), 37.1 (C14), 36.3 (C8), 35.8 (C17), 34.8 (C22), 32.9 (C18), 32.0
(C10), 25.3 (C11), 23.0 (Me16), 18.8 (Me14), 17.7 (Me22), 17.2 (Me16),
14.4 (Me18), 14.0 (Me12), 10.4 ppm (Me20); HRMS (ESI+) m/z: calcd
for C33H55O6: 547.3999 [M+H]+, found: 547.4013.
11.0 Hz; H24), 5.66–5.81 (2H, m, H7; H11), 5.63 (1H, dd, J=6.1,
16.2 Hz; H5), 5.58 (1H, d, J=11.3 Hz; H2), 5.45 (1H, d, J=10.1 Hz;
NH), 5.34 (1H, d, J=10.1 Hz; H3ꢂ), 5.26 (1H, t, J=10.4 Hz; H23), 5.20
(1H, dd, J=2.5, 8.9 Hz; H21), 5.11 (1H, d, J=16.8 Hz; H26a), 5.03 (2H,
d, J=10.6 Hz; H10, H26b), 4.89 (1H, d, J=10.1 Hz; H15), 4.41 (1H, d,
J=5.5 Hz; H2ꢂ), 4.33 (1H, d, J=5.1 Hz; H9), 3.11–3.18 (1H, m; H6),
3.05 (2H, d, J=5.5 Hz; H13, C2ꢂ-OH), 2.99 (2H, t, J=9.2 Hz; H19,
H22), 2.71 (1H, t, J=2.7 Hz; H12), 2.61 (1H, q, J=6.4 Hz; H14), 2.45–
2.56 (2H, m; H17a, H18), 1.94 (3H, s; Me16), 1.89–1.93 (1H, obsm;
H20), 1.81 (1H, dt, J=2.8, 13.1 Hz; H8a), 1.70 (1H, d, J=11.1 Hz; H8a),
1.65 (1H, dt, J=2.8, 13.0 Hz; H17b), 1.34 (3H, d, J=7.1 Hz; Me12), 1.28
(9H, s; CACTHNUGTRENUNG(CH3)3), 1.10 (3H, d, J=7.1 Hz; Me6), 1.08 (3H, d, J=6.9 Hz;
Me20), 1.06 (3H, d, J=6.7 Hz; Me14), 0.88 (3H, d, J=6.5 Hz; Me18),
0.77 ppm (3H, d, J=6.7 Hz; Me22); 13C NMR (125 MHz, CD2Cl2): d=
173.2 (C1ꢂ), 166.3 (C1), 156.3 (tBuOC(O)NHR), 143.9 (C3), 142.9 (C5),
140.4 (Ar), 134.8 (C10, C23), 133.8 (C16), 132.9 (C25), 130.5 (C24), 129.7
(C11), 129.4 (C15), 129.3 (Ar), 128.5 (Ar), 128.0 (C4), 127.4 (2C, Ar),
118.15 (C2), 118.10 (C26), 81.1 (CMe3), 80.1 (C13), 76.7 (C21), 76.5
(C19), 75.7 (C7), 73.5 (C2ꢂ), 63.9 (C9), 56.8 (C3ꢂ), 38.7 (C6), 37.8 (C17),
37.51 (C20), 37.47 (C14), 35.3 (C12), 35.1 (C8), 35.0 (C6), 31.5 (C18),
28.6 (3C, CMe3), 23.5 (Me16), 19.3 (Me14), 19.0 (Me12), 17.3 (Me22),
12.3 (Me6), 11.5 (Me18), 10.0 ppm (Me20); HRMS (ES+): m/z: calcd for
C47H69NO10Na: 830.4819 [M+Na]+, found: 830.4858.
Acetonide 18: Rf =0.66 (40% EtOAc); Rt =16 min (25% EtOAc/
hexane); [a]D20 =ꢀ20.0 (c=0.06 in CHCl3); IR (neat): n˜max =3395, 2923,
1
2853, 1713, 1641, 1456 cmꢀ1; H NMR (500 MHz, C6D6): d=7.60 (1H, dd,
J=11.0, 15.0 Hz; H4), 6.67 (1H, ddd, J=9.5, 10.6, 16.5 Hz; H25), 6.24
(1H, t, J=11.0 Hz; H3), 5.99 (1H, t, J=10.9 Hz; H24), 5.77 (1H, dd, J=
7.0, 15.9 Hz; H5), 5.53–5.68 (3H, m; H2, H10, H11), 5.31 (1H, t, J=
10.9 Hz; H23), 5.23 (1H, dd, J=2.3, 9.1 Hz; H21), 5.10 (1H, d, J=
16.8 Hz; H26a), 5.03 (1H, d, J=10.5 Hz; H26b), 4.95 (1H, d, J=10.5 Hz;
H15), 4.58 (1H, dq, J=6.4, 9.9 Hz; H9), 3.87 (1H, ddd, J=3.2, 6.4,
9.0 Hz; H7), 3.08 (1H, d, J=9.5 Hz; H19), 3.03 (1H, dq, J=6.4, 14.9 Hz;
H22), 2.95 (1H, dd, J=3.7, 7.8 Hz; H13), 2.66–2.74 (1H, m; H12), 2.62
(1H, q, J=8.2 Hz; H14), 2.50–2.56 (1H, m; H6), 2.43–2.50 (1H, m; H18),
2.28 (1H, t, J=12.3 Hz; H17a), 1.98 (1H, ddd, J=2.8, 7.3, 9.6 Hz; H20),
1.89–1.95 (1H, m; H17b), 1.86 (3H, s; Me16), 1.79 (1H, ddd, J=5.9, 9.1,
Double hybrid 33: Rf =0.63 (80% EtOAc/petroleum ether); Rt =9.1 min
(8% IPA/hexane); [a]D20 =+6.6 (c=0.03 in CHCl3); IR (neat): n˜max =3363,
2922, 2853, 1715, 1655, 1517, 1457 cmꢀ1 1H NMR (500 MHz, [D7]DMF):
;
d=8.71 (1H, d, J=9.1 Hz; NH), 7.99 (2H, d, J=7.3 Hz; Ar), 7.55–7.61
(3H, m; Ar), 7.52 (2H, t, J=7.8 Hz; Ar), 7.41 (2H, t, J=7.5 Hz; Ar),
7.33 (1H, t, J=7.3 Hz; Ar), 7.20 (1H, t, J=13.1 Hz; H4), 6.72–6.81 (2H,
m; H3, H25), 6.24 (1H, dd, J=6.1, 15.8 Hz; H5), 6.09 (1H, t, J=10.9 Hz;
H24), 6.05 (1H, d, J=9.5 Hz; C2ꢂ-OH), 5.79 (1H, t, J=9.5 Hz; H11),
5.73 (1H, t, J=9.2 Hz; H9), 5.68–5.71 (1H, obsm; H3ꢂ), 5.67 (1H, obsd,
J=10.4 Hz; H2), 5.38 (1H, t, J=10.7 Hz; H23), 5.30 (1H, obsd, J=
15.8 Hz; H26a), 5.29 (1H, obst, J=9.6 Hz; H10), 5.20 (1H, d, J=
10.4 Hz; H26b), 5.07 (1H, t, J=5.8 Hz; H21), 4.91 (1H, d, J=10.2 Hz;
H15), 4.81 (1H, d, J=5.6 Hz; C13-OH), 4.71 (1H, d, J=5.3 Hz; C19-
OH), 4.63 (1H, t, J=4.4 Hz; H2ꢂ), 4.53 (1H, d, J=5.3 Hz; C7-OH), 3.21–
3.28 (1H, m; H22), 3.13–3.18 (1H, m; H19), 3.10 (1H, dd, J=6.1, 9.5 Hz;
H13), 2.57 (1H, q, J=6.1 Hz; H6), 2.50 (1H, t, J=7.5 Hz; H12), 2.36
(1H, q, J=8.5 Hz; H14), 2.00 (2H, q, J=6.1 Hz; H18, H20), 1.69 (3H, s;
Me16), 1.57 (1H, d, J=12.1 Hz; H17a), 1.48 (1H, t, J=11.2 Hz; H8a),
1.41 (1H, dt, J=3.2, 10.4 Hz; H8b), 1.25–1.31 (1H, m; H17b), 1.13 (3H,
d, J=7.1 Hz; Me12), 1.05 (6H, t, J=6.3 Hz; Me6, Me20), 0.99 (3H, d,
J=6.8 Hz; Me22), 0.96 (3H, d, J=6.6 Hz; Me14), 0.74 ppm (3H, d, J=
6.7 Hz; Me18); 13C NMR (125 MHz, [D7]DMF): d=172.0, 167.8, 166.8,
145.9, 144.0, 140.9, 135.1, 134.1, 133.7, 133.5, 133.1, 132.3, 130.7, 130.6,
129.5, 129.1 (2C), 129.0 (2C), 128.2 (2C), 128.1 (2C), 128.0, 127.3, 118.2,
117.8, 79.1, 78.8, 75.4, 75.0, 70.2, 68.1, 56.9, 43.0, 38.0, 37.8, 37.3, 36.6,
34.6, 32.7, 23.2 (2C), 23.1, 19.4, 18.7, 18.0, 14.3, 13.6, 12.3, 10.0 ppm;
HRMS (ES+): m/z: calcd for C49H66NO9: 812.4738 [M+H]+, found:
812.4734.
14.9 Hz; H8a), 1.41 (3H, s; CACHTUNTRGENNUG(CH3)2), 1.38 (3H, s; CACHTUNTGREN(NUGN CH3)2), 1.28–1.35
(1H, m; H8b), 1.24 (3H, d, J=6.8 Hz; Me6), 1.15 (3H, d, J=7.2 Hz;
Me20), 1.06 (3H, d, J=6.9 Hz; Me12), 1.03 (3H, d, J=6.9 Hz; Me14),
0.95 (3H, d, J=6.8 Hz; Me18), 0.80 ppm (3H, d, J=7.3 Hz; Me22);
13C NMR (125 MHz, C6D6): d=165.8, 144.3, 143.8, 135.0, 134.6, 132.9,
132.8, 131.9, 130.3, 127.8, 117.8, 117.7, 100.6, 79.9, 76.0, 75.2, 68.2, 67.9,
63.9, 40.6, 37.6, 37.5, 36.2, 35.1, 34.2, 31.3, 25.9, 25.2, 24.7, 23.3, 19.5, 19.3,
17.0, 11.6, 10.4 ppm; HRMS (ESI+): m/z: calcd for C36H56O6Na:
607.3975 [M+Na]+, found: 607.3994.
Triple hybrid 31: Rf =0.63 (80% EtOAc/petroleum ether); Rt =15.0 min
(8% IPA/hexane); [a]2D0 ==+23.3 (c=0.03 in CHCl3); IR (neat): n˜max
=
3348, 2923, 2853, 1711, 1647, 1520, 1461 cmꢀ1 1H NMR (500 MHz,
;
[D7]DMF): d=8.83 (1H, d, J=8.9 Hz; NH), 8.00 (2H, d, J=8.3 Hz; Ar),
7.60 (2H, d, J=7.8 Hz; Ar), 7.57 (2H, d, J=7.6 Hz; Ar), 7.50 (2H, t, J=
7.7 Hz; Ar), 7.37–7.43 (1H, m; Ar), 7.32 (1H, t, J=7.5 Hz; Ar), 7.23
(1H, t, J=12.3 Hz; H4), 6.70–6.80 (2H, m; H3, H25), 6.24 (1H, dd, J=
5.8, 15.6 Hz; H5), 6.05–6.13 (1H, m; H24), 5.77 (1H, dd, J=2.9, 9.0 Hz;
H11), 5.65–5.72 (2H, m; H2, H3ꢂ), 5.36 (1H, d, J=9.0 Hz; H23), 5.31–
5.35 (1H, m; H7), 5.28 (2H, d, J=16.3 Hz; H10, H26a), 5.18 (1H, d, J=
10.2 Hz; H26b), 5.07 (1H, t, J=5.8 Hz; H21), 4.98 (1H, d, J=10.2 Hz;
H15), 4.70 (1H, d, J=2.8 Hz; C13-OH), 4.62 (1H, d, J=4.1 Hz; C19-
OH), 4.55–4.61 (2H, m; H9, H2ꢂ), 3.18–3.26 (1H, m; H22), 3.08–3.16
(2H, t, J=10.2 Hz; H13, H19), 2.54–2.61 (1H, m; H6), 2.41–2.49 (1H, m;
H12), 2.24–2.32 (1H, m; H14), 2.02–2.08 (1H, m; H18), 1.99 (1H, q, J=
6.1 Hz; H20), 1.74 (3H, s; Me16), 1.55 (2H, q, J=11.2 Hz; H8a, H17a),
1.37–1.43 (1H, m; H8b), 1.33–1.37 (1H, m; H17b), 1.15 (3H, d, J=
7.1 Hz; Me12), 1.06 (3H, d, J=6.9 Hz; Me20), 1.05 (3H, d, J=6.9 Hz;
Me6), 0.99 (6H, t, J=6.3 Hz; Me14, Me22), 0.74 ppm (3H, d, J=6.3 Hz;
Me18); HRMS (ES+): m/z: calcd for C49H66NO9: 812.4738 [M+H]+,
found: 812.4736.
Double hybrid 34: Rf =0.56 (70% EtOAc/petroleum ether); Rt =9.5 min
(7% IPA/hexane); [a]D20 =+6.0 (c=0.03 in CHCl3); IR (neat): n˜max =3433,
1
2963, 2920, 1694, 1498, 1456 cmꢀ1; H NMR (500 MHz, CD2Cl2): d=7.36–
7.42 (4H, m; Ar), 7.29–7.34 (1H, m; Ar), 7.28 (1H, dd, J=4.4, 15.4 Hz;
H4), 6.64 (1H, ddd, J=10.9, 11.0, 16.9 Hz; H25), 6.54 (1H, t, J=11.0 Hz;
H3), 6.08 (1H, dd, J=7.0, 15.6 Hz; H5), 5.99 (1H, t, J=11.0 Hz; H24),
5.65 (1H, obsdd, J=8.6, 11.0 Hz; H11), 5.58–5.63 (1H, m; H9), 5.50
(2H, d, J=11.2 Hz; H2, NH), 5.27–5.35 (2H, m; H10, H23), 5.15–5.20
(2H, m; H26a, H3ꢂ>), 5.09 (1H, d, J=10.0 Hz; H26b), 4.99 (2H, dd, J=
2.7, 9.0 Hz; H15, H21), 4.44 (1H, d, J=4.5 Hz; H2ꢂ), 4.00 (1H, d, J=
9.8 Hz; H7), 3.68 (1H, brs; OH), 3.24 (1H, dd, J=3.4, 8.5 Hz; H13), 3.13
(1H, d, J=4.6 Hz; C2ꢂ-OH), 3.06 (2H, d, J=7.6 Hz; H19, H22), 2.62–
2.68 (1H, m; H12), 2.49–2.58 (2H, m; H6, H14), 2.05–2.13 (2H, m;
H17a, H18), 1.95 (1H, ddd, J=2.5, 3.0, 6.7 Hz; H20), 1.75 (1H, d, J=
7.8 Hz; H17b), 1.65 (3H, s; Me16), 1.47–1.60 (2H, m; H8a, H8b), 1.42
Double hybrid 32: Rf =0.56 (70% EtOAc/petroleum ether); Rt =13.5 min
(7% IPA/hexane); [a]2D0 =ꢀ20.0 (c=0.02 in CHCl3); IR (neat): n˜max
=
3450, 2963, 2918, 1696, 1498, 1457 cmꢀ1 1H NMR (500 MHz, C6D6): d=
;
7.68 (1H, t, J=13.5 Hz; H4), 7.38 (2H, d, J=7.4 Hz; Ar), 7.11 (2H,
obsd, J=7.7 Hz; Ar), 7.05 (1H, t, J=7.4 Hz; Ar), 6.66 (1H, ddd, J=
10.7, 10.8, 16.8 Hz; H25), 6.13 (1H, t, J=11.0 Hz; H3), 5.98 (1H, t, J=
(9H, s; CACTHNUGTRENUNG(CH3)3), 1.16 (6H, t, J=6.9 Hz; Me6, Me12), 1.12 (3H, d, J=
6.7 Hz; Me20), 1.01 (3H, d, J=6.7 Hz; Me22), 0.99 (3H, d, J=6.8 Hz;
Me14), 0.74 ppm (3H, d; Me18); 13C NMR (125 MHz, CD2Cl2): d=173.0
470
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 459 – 473