1210
P. J. Montoya-Peleaz et al. / Bioorg. Med. Chem. Lett. 15 (2005) 1205–1211
29.35, 29.45, 29.49, 29.52, 32.6, 63.0, 67.8, 114.4, 120.4,
129.3, 159.1. MS (+TOF) m/z 287 [M+Na]+; HRMS
[M+Na]+, found: 287.1986. C17H28O2Na requires m/z,
287.1981.
saturated Na2SO4 (50 mL · 3), water (50 mL · 2), and
saturated NaCl (50 mL · 2), dried over Na2SO4, and
concentrated to yield a yellow oil. The product was puri-
fied by column chromatography {3:1 (v/v) ethyl acetate–
petroleum ether, then 100% ethyl acetate} to give a clear
1
7.3. Dibenzyl 11-phenoxyundecyl phosphate (9)
oil (0.617 mg, 88%). H NMR (CDCl3) d 1.70 (s, 3H),
2.02 (m, 9H), 3.93 (dd, J = 12.5, 2.2 Hz, 1H), 4.00 (m,
1H), 4.13 (dd, J = 12.5, 3.9 Hz, 1H), 4.36 (m, 1H),
Compound 10 (508 mg, 1.92 mmol) and tetrazole
(2 equiv, 271 mg, 3.84 mmol) were dissolved in dry
CH2Cl2 (20 mL) and the solution was cooled to
5.10 (m, 6H), 5.66 (m, 2H), 7.34 (m, 10H). 13C NMR
4
(CDCl3) d 20.52, 20.58, 20.61, 22.7, 51.8 (d, JCP
=
7.6 Hz), 61.2, 67.3, 69.6, 69.9 (app t, JCP = 5.5 Hz),
3
ꢀ30 ꢁC.
Bis(benzyloxy)(diisopropylamino)phosphine
3
70.1, 96.2 (d, JCP = 6.6 Hz), 128.0, 128.1, 128.77,
(2 equiv, 1.219 g, 3.84 mmol) was then added drop wise
over a 2 min period. The mixture was then stirred at rt
for 15 h, cooled to ꢀ40 ꢁC, and 77% m-CPBA (5 equiv,
2.16 g, 9.6 mmol) was added. The solution was stirred
for 1 h at 0 ꢁC, then for a further hour at rt. After addi-
tion of ethyl acetate (100 mL) the solution was washed
with saturated aqueous Na2SO3 (50 mL · 3), water
(50 mL · 2), and saturated NaCl (50 mL · 2), dried over
Na2SO4, and concentrated to yield a yellow oil. The
product was purified by column chromatography {2:3
(v/v) ethyl acetate–petroleum ether} to yield a white
4
4
128.81, 128.9, 135.2 (d, JCP = 6.5), 135.3 (d, JCP
=
6.3 Hz), 169.1, 170.1, 170.5, 171.1. 31P NMR (CDCl3)
d ꢀ2.3. MS (+TOF) m/z 630 (M++Na); HRMS
[M+Na]+, found: 630.1700. C28H34NO12NaP requires
m/z, 630.1710.
7.6. 3,4,6-Tri-O-acetyl-2-acetamido-2-deoxy-a-D-gluco-
pyranosyl dihydrogen phosphate (3)
Compound 5 (251 mg, 0.413 mmol) was dissolved in
deoxygenated methanol (15 mL) and 10% Pd/C
(300 mg) was added. The solution was stirred overnight
under an H2 atmosphere. The Pd/C was removed by fil-
tration through a Celite plug, and the solvent was evap-
1
solid (751 mg, 74%). H NMR (CDCl3) d 1.26–1.45 (m,
12H), 1.52 (m, 2H), 1.68 (m, 2H), 1.81 (m, 2H), 3.97–
4.04 (m, 4H), 5.14 (m, 4H), 6.97 (m, 3H), 7.30–7.45
(m, 12H). 13C NMR (CDCl3) d 25.2, 25.9, 29.0, 29.2,
3
1
29.26, 29.34, 29.4, 30.0, 67.8 (app t, JCP = 6.3 Hz),
68.9 (d, JCP = 5.6 Hz), 114.4, 120.3, 127.8, 128.3,
orated to yield a white solid (170 mg, 96%). H NMR
3
(CD3OD) d 1.96 (s, 3H), 2.01 (s, 3H), 2.03 (s, 3H),
2.07 (s, 3H), 4.14 (dd, J = 12.3, 2.1 Hz, 1H), 4.25 (m,
1H), 4.32 (m, 2H), 5.11 (t, J = 10 Hz, 1H), 5.31 (dd,
J = 10.9, 9.3 Hz, 1H), 5.60 (dd, 6.2, 3.3 Hz, 1H). 13C
NMR (CD3OD) d 20.57, 20.62, 20.7, 22.4, 53.1, 62.7,
69.7, 70.3, 71.5, 96.0 (d, J = 6.2 Hz), 171.2, 172.0,
172.4, 173.7. 31P NMR (CD3OD) d ꢀ2.0. MS (ꢀTOF)
m/z 426 [MꢀH]ꢀ; HRMS [MꢀH]ꢀ, found: 426.0805.
C14H22NO12P requires m/z, 426.0806.
4
128.4, 129.3, 135.9 (d, JCP = 7.0 Hz), 159.0. 31P NMR
(CDCl3) d ꢀ0.45. MS (+TOF) m/z 547 [M+Na]+;
HRMS [M+Na]+, found: 547.2570. C31H41O5PNa re-
quires m/z, 547.2583.
7.4. 11-Phenoxyundecyl dihydrogen phosphate (4)
Compound 9 (517 mg, 0.986 mmol) was dissolved in
deoxygenated methanol (15 mL) and 10% Pd/C
(200 mg) was added. The solution was stirred overnight
under a H2 atmosphere. The Pd/C was removed by fil-
tration through a Celite plug, and the solvent was evap-
7.7. Ammonium P1-3,4,6-tri-O-acetyl-2-acetamido-2-
deoxy-a-D-glucopyranosyl P2–11-phenoxyundecyl hydro-
gen diphosphate (2)
1
orated to yield a white solid (317 mg, 93%). H NMR
(CD3OD) d 1.34–1.52 (m, 12H), 1.68 (app. quin, 2H),
1.78 (app. quin, 2H), 3.97 (app. q, 4H), 6.91 (m, 3H),
7.24 (m, 2H). 13C NMR (CD3OD) d 26.7, 27.2, 30.35,
30.47, 30.53, 30.65, 30.69, 31.50, 31.58, 67.7 (d,
3JCP = 6.0 Hz), 68.9, 115.5, 121.5, 130.4, 160.6. 31P
NMR (CD3OD) d 0.33. MS (+TOF) m/z 383 [M+K]+;
HRMS [M+K]+, found: 383.1379. C17H29O5PK re-
quires m/z, 383.1384.
Both sugar head group 3 (250 mg, 0.589 mmol) and tail
4 (1.1 equiv, 223 mg, 0.648 mmol) were dried separately
by coevaporation (·3) from toluene (3 mL)–diisopropyl-
amine (3 drops). Compound 4 was left on a vacuum line
for another 30 min, then dry THF (15 mL) was
added followed by 1,10-carbonyldiimidazole (4.3 equiv,
417 mg, 2.53 mmol); the solution was stirred at rt for
1.5 h. Dry methanol (212 lL) was added, and the solu-
tion was stirred for a further hour. The solvent was
removed under reduced pressure and the residue was
kept on a vacuum line for 1 h (no bubbling). A solution
of compound 3 in dry THF (15 mL) was added, the
reaction was stirred for 48 h, and evaporated. The crude
product was purified by a Sephadex G-15 size-exclusion
column using methanol (0.1% NH4HCO3) as eluent to
yield a white solid (0.365 mg, 80 %). 1H NMR (CD3OD)
d 1.26–1.45 (m, 12H), 1.50 (m, 2H), 1.69 (m, 2H), 1.79
(m, 2H), 2.06 (m, 12H), 3.43 (m, 2H), 3.96 (m, 3H),
4.21 (m, 2H), 4.56–4.69 (m, 3H), 5.12 (t, J = 9.7 Hz,
1H), 5.33 (t, J = 9.7 Hz, 1H), 5.66 (dd, J = 3.3, 7.3 Hz,
1H), 6.92 (m, 3H), 7.25 (t, J = 8.3 Hz, 2H), 8.75 (d,
J = 8.6 Hz, 1H). 13C NMR (CD3OD) d 19.5, 20.6,
7.5. 3,4,6-Tri-O-acetyl-2-acetamido-1-O-[bis(benzyl-
oxy)phosphoryl]-2-deoxy-a-D-glucopyranose (5)
Compound 6 (0.508 mg, 1.16 mmol) and tetrazole
(10 equiv, 832 mg, 11.6 mmol) were dissolved in dry
CH2Cl2 (20 mL) and the solution was cooled to
ꢀ20 ꢁC.
Bis(benzyloxy)(diisopropylamino)phosphine
(5 equiv, 1.84 g, 5.8 mmol) was then added drop wise
over a 2 min period. The mixture was stirred at rt for
5 h, cooled to ꢀ40 ꢁC, and 77% m-CPBA (10 equiv,
2.6 g, 11.6 mmol) was added. The solution was stirred
for 30 min at 0 ꢁC, then overnight at rt. After addition
of ethyl acetate (100 mL) the solution was washed with