A solution of azide 7 (290 mg, 0.36 mmol) in 10 mL of benzene
with H2O (1 drop) was treated with Ph3P (236 mg, 0.90 mmol) and
stirred overnight at RT. After TLC indicated the complete conver-
sion of the azide to the amine, the reaction mixture was concen-
trated in vacuo. The residue was redissolved in CH2Cl2 (5 mL), treat-
ed with Boc2O (196 mg, 0.90 mmol) and Et3N (150 mL, 1.0 mmol),
and stirred overnight at RT. The reaction was quenched with satu-
rated aq NH4Cl (10 mL) and the product was extracted with CH2Cl2
(2ꢃ10 mL). The combined organic layers were dried (Na2SO4), fil-
tered and concentrated in vacuo. Purification by chromatography
(hexane/EtOAc, 6:1) gave N-Boc-protected compound 8 as a white
solid (250 mg, 79%): [a]D20 =+62.4 (c=1.14 in CHCl3); Rf =0.18
mixture was quenched with saturated aq NH4Cl (10 mL) and ex-
tracted with EtOAc (2ꢃ10 mL). The combined organic layers were
dried (Na2SO4), filtered and concentrated in vacuo. Purification by
chromatography (hexane/EtOAc, 4:1) afforded benzophenone-
linked product 10 as a white solid (33 mg, 85%): [a]2D0 =+46.71
(c=1.55 in CHCl3); Rf =0.48 (EtOAc/hexane, 1:2); 1H NMR (CDCl3):
d=1.16–1.48 (m, 28H), 1.81 (m, 2H), 1.97 (q, 2H, J=7.2 Hz), 3.68
(dd, 1H, J=4.0, 9.5 Hz), 4.00 (m, 1H), 4.04 (t, 2H, J=7.2 Hz), 4.14
(m, 1H), 4.35 (t, 1H, J=6.8 Hz), 4.42 (dd, 1H, J=6.8, 11.2 Hz), 4.66
(dd, 1H, J=7.5, 12.3 Hz), 4.80 (m, 1H), 4.83 (d, 1H, J=8.0 Hz), 5.28
(m, 1H), 5.38 (dd, 1H, J=7.5, 15.0 Hz), 5.65 (dd, 1H, J=3.4,
10.2 Hz), 5.72 (m, 1H), 5.78 (dd, 1H, J=7.8, 10.2 Hz), 6.01 (d, 1H,
J=3.0 Hz), 6.97 (d, 2H, J=9.2 Hz), 7.25–8.13 ppm (m, 27H);
13C NMR (CDCl3): d=26.0, 27.1, 28.3, 28.3, 28.8, 29.0, 29.1, 29.3,
29.4, 29.6, 32.2, 38.8, 52.3, 61.9, 64.8, 68.0, 68.3, 69.9, 71.3, 71.6,
73.4, 79.3, 101.4, 114.0, 126.2, 127.9–133.6, 136.6, 138.4, 155.3,
162.9, 165.3–166.0, 176.9, 195.6 ppm; HRMS: m/z [M+Na]+ calcd
for C70H77NO16Na: 1210.5140, found: 1210.5141.
1
(EtOAc/hexane, 1:3); H NMR (CDCl3): d=1.20 (s, 9H), 1.32 (s, 9H),
3.67 (dd, 1H, J=4.3, 9.8 Hz), 4.00 (m, 1H), 4.13 (dd, 1H, J=3.3,
9.8 Hz), 4.34 (m, 1H), 4.41 (dd, 1H, J=6.7, 11.4 Hz), 4.63 (dd, 1H,
J=6.6, 11.2 Hz), 4.80 (m, 1H), 4.83 (d, 1H, J=7.8 Hz), 5.20 (m, 2H),
5.35 (t, 1H, J=6.2 Hz), 5.63 (dd, 1H, J=3.4, 10.4 Hz), 5.76 (m, 2H),
6.00 (d, 1H, J=3.4 Hz), 7.21–8.12 ppm (m, 20H); 13C NMR (CDCl3):
d=27.1, 28.3, 38.8, 52.2, 62.0, 67.9, 69.9, 71.5, 73.4, 79.4, 101.4,
118.3, 128.3–130.0, 133.3, 133.6, 155.3, 165.2–166.0, 176.9 ppm;
HRMS: m/z [M+Na]+ calcd for C49H53NO14Na: 902.3364, found:
902.3354.
(2S,3R,4E)-2-tert-Butoxycarbonylamino-3-hydroxy-13-O-(4’-ben-
zoylphenyl)-1-O-b-d-galactopyranosy1-4-tridecene (11): Na(s)
(5 mg) was dissolved in dry MeOH (3 mL) and added to a solution
of 10 in dry MeOH/THF (5:1, 6 mL). The reaction mixture was
stirred for 2 d at RT. Dowex 50W-X8 resin (prewashed thoroughly
with MeOH) was added to neutralize the reaction mixture, which
was then filtered and concentrated. Purification by chromatogra-
phy (CHCl3/MeOH, 10:1) gave 11 as a white solid (15.6 mg, 90%):
[a]2D0 =ꢀ1.05 (c=0.76 in CHCl3/MeOH, 3:1); Rf =0.4 (CHCl3/MeOH,
10-Bromo-1-decene:[15]
A
solution of 9-decen-1-ol (5.0 g,
32.4 mmol) and Ph3P (11.0 g, 42.1 mmol) in CH2Cl2 (50 mL) was
cooled to 08C and treated in small portions with N-bromosuccin-
imide (7.5 g, 42.1 mmol) over a period of 1 h at 08C. The mixture
was filtered through a silica gel pad, washed with CH2Cl2 (50 mL),
concentrated, and purified by vacuum distillation. The product
boiling at 30–358C (2 mm Hg) was collected, providing 10-bromo-
1-decene as a colorless liquid (5.8 g, 83%): Rf =0.71 (EtOAc/hexane,
1:5); 1H NMR (CDCl3): d=1.30 (m, 10H), 1.85 (p, 2H, J=7.2 Hz),
2.03 (q, 2H, J=7.0 Hz), 3.40 (t, 2H, J=7.0 Hz), 4.96 (m, 2H),
5.81 ppm (m, 1H); 13C NMR (CDCl3): d=28.2, 28.8, 28.9, 29.0, 29.2,
29.3, 32.8, 33.6, 33.8, 34.0, 114.2, 138.9 ppm.
1
3:1); H NMR (CDCl3/CD3OD, 20:1): d=1.27–1.47 (m, 19H), 1.80 (p,
2H, J=6.6 Hz), 2.01 (q, 2H, J=6.4 Hz), 3.55 (m, 1H), 3.62 (m, 2H),
3.70 (m, 2H), 3.82 (m, 2H), 3.91 (m, 1H), 4.02 (t, 2H, J=6.4 Hz),
4.05 (m, 1H), 4.16 (m, 1H), 4.28 (d, 1H, J=7.8 Hz), 5.48 (dd, 1H, J=
6.9, 15.2 Hz), 5.73 (dt, 1H, J=6.7, 14.0 Hz), 6.94 (d, 2H, J=8.8 Hz),
7.37–8.07 ppm (m, 7H); 13C NMR (CDCl3/CD3OD 20:1): d=26.0,
28.4, 29.1, 29.2, 29.3, 29.4, 32.4, 54.6, 61.3, 64.8, 67.9, 68.2, 68.9,
69.4, 71.0, 72.5, 73.3, 74.6, 79.6, 103.8, 114.0, 126.2, 127.5–132.6,
138.2, 156.3, 162.9, 195.8 ppm; HRMS: m/z [M+Na]+ calcd for
C37H53NO11Na: 710.3516, found: 710.3515.
(2S,3R,4E)-2-tert-Butoxycarbonylamino-3-O-pivaloyl-13-bromo-1-
O-(2’,3’,4’,6’-tetra-O-benzoyl-b-d-galactopyranosy1)-4-tridecene
(9): 10-Bromo-1-decene (183 mg, 0.84 mmol) was added to a solu-
tion of alkene 8 (185 mg, 0.21 mmol) in dry CH2Cl2 (8 mL) and the
solution was flushed twice with N2 (10 min each time). The reaction
mixture was treated with Grubbs’ second generation catalyst
(53.6 mg, 0.063 mmol) at RT under N2 and stirred for 16 h at reflux.
The reaction was cooled to RT and concentrated in vacuo. Purifica-
tion by chromatography (hexane/EtOAc, 4:1) gave 9 as a white
solid (142 mg, 63%): [a]D20 =+41.5 (c=0.67 in CHCl3); Rf =0.68
(EtOAc/hexane, 1:2); 1H NMR (CDCl3): d=1.17–1.39 (m, 28H), 1.83
(p, 2H, J=7.0 Hz), 1.94 (q, 2H, J=6.9 Hz), 3.39 (t, 2H, J=6.9 Hz),
3.67 (dd, 1H, J=3.9, 9.8 Hz), 3.97 (m, 1H), 4.13 (dd, 1H, J=3.3,
10.0 Hz), 4.34 (m, 1H), 4.39 (dd, 1H, J=6.8, 11.0 Hz), 4.63 (dd, 1H,
J=6.2, 11.0 Hz), 4.76 (m, 1H), 4.80 (d, 1H, J=8.0 Hz), 5.25 (m, 1H),
5.34 (dd, 1H, J=7.5, 15.7 Hz), 5.62 (dd, 1H, J=3.6, 10.4 Hz), 5.68
(m, 1H), 5.74 (dd, 1H, J=8.0, 10.5 Hz), 5.98 (d, 1H, J=2.8 Hz),
7.21–8.12 ppm (m, 20H); 13C NMR (CDCl3): d=27.1, 28.2, 28.3, 28.7,
28.8, 29.0, 29.2, 32.8, 34.0, 38.8, 52.2, 61.9, 67.9, 69.9, 71.5, 73.3,
79.3, 101.4, 124.9, 128.3–130.0, 133.3, 133.6, 136.5, 155.3, 165.3–
166.0, 176.9 ppm; HRMS: m/z [M+Na]+ calcd for C57H68BrNO14Na:
1092.3721, found: 1092.3723.
(2S,3R,4E)-2-Amino-3-hydroxy-13-O-(4’-benzoylphenyl)-1-O-b-d-
galactopyranosy1-4-tridecene (1): A mixture of compound 11
(12 mg, 0.017 mmol) and 1m HCl in 90% aqueous HOAc (50 mL)
was stirred at RT in CH2Cl2 (10 mL) for 35 min. After concentration,
the residue was diluted with MeOH (5 mL) and again concentrated
to afford the hydrochloride salt of 1 as a white solid (10.2 mg,
94%): [a]2D0 =ꢀ6.22 (c=0.45 in CHCl3/MeOH, 4:1); Rf =0.08 (CHCl3/
MeOH, 3:1); 1H NMR (CDCl3/CD3OD, 20:1): d=1.24–1.39 (m, 10H),
1.72 (p, 2H, J=6.6 Hz), 2.01 (q, 2H, J=6.9 Hz), 3.27 (m, 1H), 3.35
(m, 1H), 3.48 (m, 2H), 3.66 (m, 2H), 3.74 (m, 1H), 3.81 (m, 1H), 3.87
(m, 1H), 3.95 (t, 2H, J=6.6 Hz), 4.21 (m, 1H), 4.37 (m, 1H), 5.34 (dd,
1H, J=5.6, 15.3 Hz), 5.73 (dt, 1H, J=6.6, 14.3 Hz), 6.86 (d, 2H, J=
8.8 Hz), 7.35–7.96 ppm (m, 7H); 13C NMR (CDCl3/CD3OD 20:1): d=
21.8, 29.8, 32.8, 32.9, 33.1, 33.2, 33.5, 36.2, 61.6, 65.5, 69.5, 72.2,
73.0, 73.4, 74.9, 76.9, 78.9, 106.9, 117.9, 130.2, 132.1, 133.5, 133.6,
135.9, 136.6, 139.4, 142.0, 166.9, 200.3 ppm; HRMS: m/z [M+Na]+
calcd for C32H45NO9Na: 610.2992, found: 610.2997.
Biology
(2S,3R,4E)-2-tert-Butoxycarbonylamino-3-O-pivaloyl-13-O-(4’’-
benzoylphenyl)-1-O-(2’,3’,4’,6’-tetra-O-benzoyl-b-d-galactopyra-
Intracellular Ca2+ mobilization measurements: The permanent
human leukemia cell line U937 was cultured in RPMI 1640 medium
with HEPES containing 10% fetal bovine serum (FBS), 2 mm gluta-
mate, and a penicillin–streptomycin solution (Sigma, St. Louis, USA)
in a humidified air/CO2 (19:1) atmosphere. Cells were diluted to 5ꢃ
nosy1)-4-tridecene (10):
A solution of bromide 9 (35 mg,
0.033 mmol), 4-hydroxybenzophenone (10 mg, 0.049 mmol) and
K2CO3 (7.0 mg, 0.049 mmol) in dry DMF (3.5 mL) was heated in a
Smith Creator microwave reactor at 1208C for 1.5 h. The reaction
ChemMedChem 2010, 5, 682 – 686
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
685