6562
S. Bachan et al. / Bioorg. Med. Chem. 21 (2013) 6554–6564
J = 4.4 Hz, OH), 2.41 (s, 1H, OH), 2.59 (d, 1H, J = 5.9 Hz, OH), 3.40
(dd, 1H, J = 5.6, 10.0 Hz), 3.48 (dd, 1H, J = 5.6, 10.0 Hz), 3.55 (m,
1H), 3.60 (m, 3H), 3.93 (m, 1H), 4.06 (t, 1H, J = 3.4 Hz), 4.24 (d,
1H, J = 7.1 Hz), 4.95 (bd, 1H, J = 10 .1 Hz), 5.00 (bd, 1H, J = 10
.1 Hz), 5.81 (m, 1H), 7.26 (m, 3H), 7.33 (bt, 6H, J = 7.8 Hz), 7.48
(bd, 6H, J = 7.3 Hz). 13C NMR (CDCl3) d 26.2, 29.1, 29.2, 29.5, 29.6,
29.8, 34.0, 62.7, 69.2, 70.2, 72.6, 73.6, 73.7, 87.2, 103.1, 114.3,
127.4, 128.1, 128.8, 139.4, 143.8.
16a), 3.51 (t, 1H, J = 9.6 Hz, H-40), 3.62 (m, 1H, H-50), 3.65 (m, 2H,
H-100a, H-16b), 3.73 (m, 1H, H-100b), 3.78 (m, 1H, H-60a), 3.87 (m,
2H, H-4, 60b), 3.94 (dd, 1H, J = 3.2, 9.0 Hz, H-30), 3.96 (bs, 1H, H-
20), 4.82 (s, 1H, H-10), 5.07 (bq, 1H, J = 6.8 Hz, H-18), 7.20 (s, 1H,
H-17). 13C NMR (CDCl3) d 14.3, 19.3, 22.9, 25.8 (two lines), 26.2,
26.3, 29.4, 29.5, 29.5, 29.6 (four lines), 29.7 (three lines), 29.8
(two lines), 30.6, 32.1, 33.6, 37.6, 62.3, 68.1, 70.3, 71.3, 71.6, 71.8,
73.5, 76.1, 78.2, 99.6, 131.4, 152.0, 174.9. HRMS (ESI) calcd for
(M+HCOO)ꢂ C37H67O11, 687.4689, found 687.4678.
To a portion of the material from the previous step (668 mg,
1.19 mmol) in MeOH (20 mL) was added Bu2SnO (308 mg,
1.20 mmol). The mixture was heated at reflux for 3 h in MeOH
and then at reflux in toluene (20 mL). The solvent was removed
in vacuo and the residue taken up in dry DMF (10 mL). CsF
(606 mg, 4.00 mmol) and C11H23Br (0.70 mL, 4.10 mmol) were
introduced, the mixture stirred at 80 °C for 15 h and then cooled
to rt, diluted with water and extracted with EtOAc. The organic
phase was dried (Na2SO4), filtered and evaporated under reduced
pressure. FCC of the residue gave 42 (560 mg, 66%). Rf = 0.8 (30%
EtOAc/petroleum ether). 1H NMR (CDCl3) d 0.90 (t, 3H, J = 7.1 Hz),
1.25–1.42 (m, 26 H), 1.67 (m, 4H), 2.05 (m, 2H), 2.32 (m, 2H),
3.28 (dd, 1H, J = 3.3, 9.4 Hz), 3.39 (dd, 1H, J = 5.5, 9.4 Hz), 3.5 (dd,
1H, J = 6.1, 9.3 Hz), 3.54–3.62 (m, 3H), 3.68 (m, 2H), 3.95 (m, 1H),
4.05 (bs, 1H), 4.26 (d, 1H, J = 7.8 Hz), 4.97 (m, 2H), 5.82 (m, 1H),
7.18–7.29 (m, 9H), 7.42 (m, 6H). 13C NMR (CDCl3) d 14.3, 22.9,
26.3, 29.1, 29.3, 29.5, 29.6, 29.7, 29.8 (two lines), 30.1, 32.1, 34.0,
63.2, 66.5, 70.0, 70.4, 71.1, 74.0, 81.4, 87.0, 103.1, 114.3, 127.3,
128.1, 128.9, 139.4, 144.1. HRMS (ESI) calcd for (M+Na)+ C46H66-
NaO6, 737.4752, found 737.4757.
4.1.23. 4-Deoxy-6-O-undecyl-lyxose-pyranoside-acetogenin
analog (5)
CM on 19 (358 mg, 0.72 mmol) and butenolide 17 (47 mg,
0.24 mmol) following the procedure described for 24, gave 25
(31 mg, 20%, Supplementary data). Processing of 25 (31 mg,
0.046 mmol) as described for 4, provided 5 (16 mg, 38%). Rf = 0.13
(60% EtOAc/Petroleum ether). 1H NMR (CDCl3) d 0.89 (t, 3H,
J = 7.1 Hz), 1.28 (m, 34H), 1.45 (d, 3H, J = 6.80 Hz), 1.48 (m, 2H),
1.55 (m, 5H), 1.79 (m, 1H), 2.41 (dd, 1H, J = 8.2, 15.1 Hz), 2.55
(bd, J = 15.1 Hz), 3.35–3.50 (m, 5H), 3.66 (m, 1H), 3.72 (bs, 1H),
3.86 (m, 2H), 4.02(m, 1H), 4.85 (s, 1H), 5.08 (q, 1H, J = 6.80 Hz),
7.18 (bs, 1H). 13C NMR (CDCl3) d 14.3, 19.3, 22.9, 25.8, 26.3, 29.5,
29.6 (three lines), 29.6 (two lines), 29.7 (three lines), 29.8, 29.9
(two lines), 31.5, 32.1, 33.6, 37.7, 65.9, 67.3, 68.0, 69.5, 70.2, 72.0,
73.5, 78.2, 100.3, 131.4, 152.0, 174.9. HRMS (ESI) calcd for
(M+NH4)+ C35H68NO8, 630.4939, found 630.4928.
4.1.24. 3,4-Dideoxy-6-O-undecyl-threose-acetogenin analog (6)
CM on 20 (27 mg, 0.061 mol) and butenolide 17 (39 mg,
0.2 mmol) following the procedure described for 24, gave 26
(14 mg, 38%, Supplementary data). Diimide reduction on 26
(14 mg, 0.023 mmol) as described for 4, provided 6 (12 mg, 84%);
Rf = 0.15 (35% EtOAc/Petroleum ether). 1H NMR (CDCl3) d 0.85
(t, 3H, J = 6.9 Hz), 1.23 (m, 34H), 1.41 (d, 3H, J = 6.8 Hz), 1.46 (m,
2H), 1.57 (m 5H), 1.64 (m, 1H), 1.73 (m, 1H), 1.97 (m, 1H), 2.05
(bs, partially buried, 1H), 2.23 (bs, 1H), 2.38 (dd, 1H, J = 8.3,
15.2 Hz), 2.52 (bd, 1H, J = 15.2 Hz), 3.36 (dd, 1H, J = 4.3, 10.4 Hz),
3.43 (m, 4H), 3.60 (bs, 1H), 3.69 (m, 1H), 3.82 (m, 1H), 3.91 (m,
1H), 4.61 (s, 1H), 5.04 (m, 1H). 13C NMR (CDCl3) d 14.3, 19.3,
21.8, 22.9, 25.2, 25.8, 26.3, 26.4, 29.5, 29.6 (two lines), 29.7 (two
lines), 29.8, 29.9, 32.1, 33.5, 37.6, 66.1, 67.7, 67.9, 70.2, 71.9,
73.9, 78.2, 99.8, 131.4, 152.0, 174.8. HRMS (ESI) calcd for
(M+Na)+ C35H64NaO7, 619.4544, found 619.4543.
4.1.21. General procedure for CM reactions: Mannose–
butenolide CM product (24)
A solution of 18 (155 mg, 0.3 mmol) and butenolide 1723,24
(20 mg, 0.1 mmol) in DCM (8 mL) was degassed using N2 for
30 min and then Grubb’s II catalyst (9 mg, 0.01 mmol) was added.
The reaction was stirred for 18 h and then concentrated in vacuo.
FCC of the residue gave 24 (44 mg, 63% from 17). Rf = 0.14 (20%
EtOAc/petroleum ether). 1H NMR (CDCl3) d 0.88 (t, 3H, J = 7.1 Hz),
1.25–1.35 (m, 26 H), 1.36 (s, 3H), 1.46 (d, 3H, J = 7.0 Hz), 1.54 (s,
3H), 1.59 (m, 6H), 1.93–2.56 (m, 6H), 3.38 (m, 2H), 3.50 (m, 1H),
3.58 (m, 1H), 3.67 (m, 1H), 3.74 (1H), 3.85 (m, 3H), 4.10, 4.11 (d,
1H, J = 7.0), 4.20 (t, 1H, J = 6.7 Hz), 5.00 (s, 1H), 5.08 (m, 1H),
5.35–5.59 (m, 2H), 7.18, 7.19 (both s, 1H, ca ratio 3:1). 13C NMR
(CDCl3) (major isomer) d 14.3, 19.3, 22.9, 26.3 (two lines), 26.6,
28.3, 29.1, 29.3 (two lines), 29.5, 29.6, 29.6 (two lines), 29.7 (two
lines), 29.8, 29.9, 30.3, 32.1, 32.7, 32.8, 32.9, 33.5, 37.3, 63.0, 68.0,
68.5, 69.9, 71.8, 75.5, 76.1, 78.2, 78.9, 97.3, 109.4, 125.2, 129.5,
131.7, 135.5, 152.0, 174.8. HRMS (ESI) calcd for (M+Na)+ C39H68-
NaO9, 703.4756, found 703.4750.
4.1.25. 2-Deoxy-6-O-undecyl-arabinose-acetogenin analog (7)
CM on 21 (426 mg, 0.62 mmol) and butenolide 17 (41 mg,
0.21 mmol) following the procedure described for 24, gave 27
(43 mg, 24%, Supplementary data). Processing of 27 (43 mg,
0.05 mmol) as described for 4, provided 7 (12 mg, 40%); Rf = 0.26
(60% EtOAc/petroleum ether); 1H NMR (CDCl3) d 0.85 (m, 3H),
1.28 (m, 34H), 1.41 (d, 3H, J = 6.8 Hz), 1.45 (m, 2H), 1.55 (m, 4H),
1.64 (dt, 1H, J = 3.6, 12.6 Hz), 2.08 (dd, 1H, J = 5.1, 12.8 Hz), 2.30
(bs, 1H), 2.37 (dd, 1H, J = 8.4, 15.2 Hz), 2.40 (bs, partially buried,
1H), 2.49 (bd, 1H, J = 15.2 Hz), 3.15 (bs, 1H), 3.31 (m, 1H), 3.47
(m, 3H), 3.58 (m, 2H), 3.67 (m, 2H), 3.82 (m, 1H), 3.96 (m, 1H),
4.85 (d, 1H, J = 3.2 Hz), 5.04 (q, 1H, J = 6.8 Hz), 7.16 (s, 1H). 13C
NMR (CDCl3) d 14.3, 19.3, 22.9, 25.7, 26.2, 26.4, 29.5 (two lines),
29.6, 29.7 (three lines), 29.8, 29.9, 32.1, 33.6, 37.1, 37.6, 67.7,
69.0, 69.2, 70.2, 72.2, 72.3, 75.5, 78.2, 97.6, 131.4, 152.0, 174.8.
HRMS (ESI) calcd for (M+Na)+ C36H66NaO8, 649.4650, found
649.4648.
4.1.22. General procedures for processing of CM products: 6-O-
undecyl-mannose-acetogenin analog (4)
To a solution of 24 (44 mg, 0.065 mmol) and TsNHNH2 (363 mg,
1.95 mmol) in DME (12 mL) at reflux, was added a solution of NaO-
Ac (426 mg, 2.60 mmol) in H2O (12 mL), over a 4 h period. The mix-
ture was then cooled, diluted with EtOAc, and washed with 1 M
HCl and saturated aqueous NaHCO3. The organic phase was dried
(Na2SO4), filtered and concentrated in vacuo. The crude residue
was taken up in DCM (5 mL) and treated with 3% AcCl in MeOH
(0.5 mL). The reaction was stirred for 1 h and then quenched with
solid NaHCO3. The mixture filtered and concentrated in vacuo. FCC
of the residue afforded 4 (15 mg, 36%, two steps). Rf = 0.3 (80%
EtOAc/Petroleum ether). 1H NMR (CDCl3) d 0.90 (6, 3H, J = 7.1 Hz,
CH3-1100), 1.26 (m, 34H, (CH2)17), 1.44 (d, 3H, J = 6.8 Hz, CH3-19),
1.48 (m, 2H, CH2-5), 1.57 (m, 4H, CH2-15, CH2-200), 2.18 (bs, 1H,
OH), 2.28 (bs, 1H, OH), 2.42 (dd, 1H, J = 8.3, 15.1 Hz, H-3a), 2.51
(bs, partially buried, 1H, OH), 2.55 (m, 1H, H-3b), 3.41 (m, 1H, H-
4.1.26. 3-O-Undecyl-galactose-acetogenin analog (8)
CM on 22 (158 mg, 0.2 mmol) and butenolide 17 (14 mg,
0.07 mmol) following the procedure described for 24, gave 28
(11 mg, 16%, Supplementary data). Processing of 28 (11 mg,