Archaeal Tetraether Glycolipid Analogues
J . Org. Chem., Vol. 64, No. 9, 1999 3149
0.86-0.91 (m, 18H), 1.06-1.42 and 1.47-1.68 (2m, 48H), 2.2
(m, 1H), 3.40-3.76 (m, 18H), 4.55 (s, 2H), 7.27-7.34 (m, 5H);
13C NMR (100 MHz, CDCl3) δ 19.72, 19.74, 22.68, 22.78, 24.74,
26.18, 26.21, 28.03, 29.56, 29.87, 37.16, 37.18, 37.42, 37.34,
39.34, 39.37, 63.17, 68.70, 68.94, 70.34, 70.81, 71.01, 71.94,
73.42, 77.99, 78.32, 127.57-138.49. Anal. Calcd for C49H92O6:
C, 75.52; H, 11.93. Found: C, 75.33; H, 11.81.
48H), 1.96-2.16 (11s, 33H), 3.37-3.63 (m, 17H), 3.72-3.82
(m, 2H), 3.84-3.92 (m, 2H), 4.05-4.16 (m, 3H), 4.19-4.27 (m,
2H), 4.33 (dd, 1H), 4.45-4.50 (m, 2H, J ) 7.63, 11.75 Hz), 4.54
(d, 1H, J ) 7.63 Hz), 4.88-5.01 (m, 3H), 5.07-5.14 (m, 3H),
5.19 (dd, 1H, J ) 9.16 Hz), 5.33-5.41 (m, 2H, J ) 3.56 Hz);
13C NMR (100 MHz, CDCl3) δ 19.63, 20.68, 20.69, 20.71, 20.72,
20.73, 20.74, 20.76, 20.77, 20.78, 20.81, 20.83, 22.60, 22.73,
24.65, 26.11, 26.14, 27.96, 29.52, 29.55, 29.62, 29.65, 29.66,
29.68, 29.70, 29.72, 29.73, 37.02, 37.08, 37.32, 37.37, 39.27,
39.31, 60.78, 62.22, 62.74, 67.01, 67.46, 68.95, 69.29, 69.71,
70.45, 71.78, 73.40, 75.12, 76.31, 76.59, 77.16, 77.61, 79.88,
81.24, 100.60, 100.80, 105.82, 169.02-170.04. To a solution of
this compound (85 mg) in CH3OH (5 mL) was added a 0.1 M
solution of sodium methoxide in CH3OH (4 mL). The mixture
was stirred for 10 h at room temperature, neutralized with
an acidic resin (Amberlite IR 120), filtered, and concentrated.
The crude product was purified by silica gel chromatography,
eluting with a mixture of EtOAc-CH3OH-H2O (7:2.5:0.5), to
yield 7 as a white solid (60 mg, 93%), Rf ) 0.53 [solvent:
3,3′-O-(1,16-Hexa d eca m eth ylen e)-2,2′-d i-O-[(R)-3,7-d i-
m eth yloctyl]-1-O-(2,3,5,6-tetr a -O-a cetyl-â-D-ga la ctofu r a n -
osyl)-sn -d iglycer ol (36). Compound 35 (145 mg, 0.186 mmol)
and pent-4-enyl 2,3,5,6-tetra-O-acetyl-R,â-D-galactofuranoside
3124 (124 mg, 0.298 mmol) were combined, rotoevaporated
twice with toluene, and then dried for 2 h under vacuum. A
solution of this mixture in dry CH2Cl2 (6 mL) at room
temperature was treated under nitrogen with N-iodosuccin-
imide (87 mg, 0.372 mmol) followed by dropwise addition of
triethysilyl trifluoromethanesulfonate (21 µL, 0.084 mmol).
The mixture was stirred until TLC analysis indicated complete
disappearance of the starting acceptor 35 (10-15 min). Several
drops of triethylamine were added to the reaction mixture until
it turned into a yellow solution. The resulting solution was
diluted with CH2Cl2, washed successively with 10% aqueous
sodium thiosulfate, 0.5% aqueous HCl, and brine, dried over
MgSO4 and rotoevaporated. The crude product was purified
by silica gel chromatography with petroleum ether-EtOAc (4:
1) to yield 3,3′-O-(1,16-hexadecamethylene)-2,2′-di-O-[(R)-3,7-
dimethyloctyl]-1-O-(2,3,5,6-tetra-O-acetyl-â-D-galactofuranosyl)-
1′-O-benzyl-sn-diglycerol as a colorless oil (164 mg, 80%), Rf
) 0.31 (solvent C); 1H NMR (400 MHz, CDCl3) δ 0.82-0.88
(m, 18H), 1.04-1.42 and 1.46-1.68 (2m, 48H), 2.05-2.12 (4s,
12H), 3.39-3.66 (m, 17H), 3.72-3.78 (dd, 1H, J ) 4.57, 10.17
Hz), 4.22 (dd, 1H, J ) 7.12, 11.70 Hz), 4.25 (dd, 1H, J ) 3.56,
6.11 Hz), 4.34 (dd, 1H, J ) 4.07 Hz), 4.55 (s, 2H), 4.99 (m,
1H), 5.06-5.09 (m, 2H), 5.39 (m, 1H), 7.27-7.34 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 19.68, 19.73, 22.68, 22.78, 24.75,
20.79, 20.83, 20.91, 24.73, 26.21, 28.03, 29.59-29.84, 37.15,
37.18, 37.44, 39.37, 62.81, 67.52, 68.93, 69.01, 69.35, 70.35,
70.51, 70.82, 71.73, 71.85, 73.41, 76.65, 77.99, 79.93, 81.29,
105.82, 127.56-138.50, 169.60, 170.03, 170.11, 170.58. A
solution of this compound (164 mg) in EtOH (3 mL) was stirred
in the presence of 10% palladium on activated charcoal (20
mg) and under an atmosphere of hydrogen gas at room
temperature until TLC analysis indicated complete disappear-
ance of the starting material. The catalyst was removed by
filtration, and the filtrate was concentrated to dryness under
vacuum to give the deprotected monoglycosylated lipid 36 as
EtOAc-CH3OH-H2O (7:2.5:0.5)]. 7: mp 195-196 °C; [R]20
D
-26.7 (c 0.78, CH3OH); 13C NMR (100 MHz, CD3OD) δ 20.18,
20.21, 23.08, 23.18, 25.84, 27.27, 29.14, 30.57-30.95, 38.16,
38.40, 40.50, 61.82, 62.45, 64.48, 68.40, 69.63, 69.75, 70.21,
70.24, 71.79, 71.96, 72.35, 72.52, 72.60, 74.62, 74.71, 76.27,
76.44, 77.03, 78.82, 79.17, 79.22, 80.47, 83.12, 84.53, 104.54,
104.99, 109.64; FABMS (m-nitrobenzyl alcohol matrix) calcd
for [M + Na]+ 1195.7907, found 1195.7880.
3,3′-O-(1,16-Hexa d eca m eth ylen e)-2,2′-d i-O-[(R)-3,7-d i-
m eth yloctyl]-1-O-(2,3,5,6-tetr a -O-a cetyl-â-D-ga la ctofu r a n -
osyl)-1′-O-(d iben zylp h osp h on o)-sn -d iglycer ol (38). To a
solution of alcohol 36 (195 mg, 0.192 mmol) in CH2Cl2 (5 mL)
were added dibenzyl diisopropylphosphoramidite (96 µL, 0.287
mmol) and 1H-tetrazole (41 mg, 0.576 mmol). After 2 h under
stirring at room temperature, the mixture was cooled to -40
°C, and a solution of 3-chloroperoxybenzoic acid (ready for use,
Acros, 70% purity with water, 95 mg, 0.384 mmol) in CH2Cl2
(3 mL) was added. The reaction mixture was heated to 0 °C
and maintained at this temperature for 20 min. The solution
was diluted with CH2Cl2 and washed with 10% aqueous
Na2S2O3, 5% aqueous NaHCO3, water, and brine. The organic
layer was dried (MgSO4) and concentrated, and the residue
was purified by flash silica gel chromatography [elution with
petroleum ether-EtOAc (7:3)] to provide compound 38 as a
colorless oil (195 mg, 80%), Rf ) 0.67 (solvent G). 38: [R]20
D
-12.3 (c 0.81, CH2Cl2); 31P NMR (162 MHz, CDCl3) δ -3.56
(s, 1P); 1H NMR (400 MHz, CDCl3) δ 0.82-0.89 (m, 18H),
1.05-1.41 and 1.46-1.65 (2m, 48H), 2.04-2.14 (4s, 12H),
3.36-3.64 (m, 15H), 3.75 (dd, 1H, J ) 4.57, 10.68 Hz), 3.99-
4.15 (2m, 2H), 4.22 (dd, 1H, J ) 7.12, 11.70 Hz), 4.26 (dd, 1H,
J ) 4.07, 6.10 Hz), 4.34 (dd, 1H, J ) 4.07 Hz), 4.99 (m, 1H),
5.03-5.09 (m, 2H), 5.39 (m, 1H), 7.28-7.37 (m, 10H); 13C NMR
(100 MHz, CDCl3) δ 19.62, 19.64, 20.68-20.83, 22.60, 22.71,
24.66, 26.10, 26.14, 27.95, 29.53-29.74, 37.01, 37.09, 37.33,
37.36, 39.28, 39.31, 62.74, 67.46, 68.95, 69.16, 69.21, 69.70,
70.44, 71.78, 76.59, 77.16, 77.61, 79.87, 81.23, 105.75, 127.87-
135.92, 169.53-170.50. Anal. Calcd for C70H117O18: C, 65.81;
H, 9.23. Found: C, 65.46; H, 9.13.
a colorless oil (137 mg, 91%), Rf ) 0.54 (solvent G). 36: [R]20
D
-16.1 (c 0.8, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 0.82-0.88
(m, 18H), 1.05-1.43 and 1.47-1.69 (2m, 48H), 2.04-2.18 (4s,
12H), 2.2 (t, 1H, J ) 6.10 Hz), 3.39-3.77 (m, 18H), 4.21 (dd,
1H, J ) 7.12, 11.70 Hz), 4.25 (dd, 1H, J ) 3.56, 5.80 Hz), 4.34
(dd, 1H, J ) 4.07 Hz), 4.99 (m, 1H), 5.06-5.09 (m, 2H), 5.39
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 19.62, 19.65, 20.68-
20.83, 22.60, 22.71, 24.66, 26.11, 26.14, 27.95, 29.48-29.80,
37.09, 37.35, 37.37, 39.27, 62.74, 63.09, 67.45, 68.63, 68.94,
69.29, 70.35, 70.44, 70.95, 71.78, 71.86, 76.58, 77.61, 78.28,
79.87, 81.21, 105.76, 169.53-170.51. Anal. Calcd for
C
56H104O15: C, 66.11; H, 10.30. Found: C, 65.87; H, 10.29.
3,3′-O-(1,16-Hexa d eca m eth ylen e)-2,2′-d i-O-[(R)-3,7-d i-
m eth yloctyl]-1-O-(â-D-ga la ctofu r a n osyl)-sn -d iglycer ol-1′-
O-p h osp h a te, Sod iu m Sa lt (8). To a solution of compound
38 (170 mg, 0.133 mmol) in CH3OH (5 mL) was added dropwise
a 0.1 M solution of sodium methoxide in CH3OH (4 mL). The
resulting mixture was stirred for 15 min at room temperature
and was treated with a solution of acetic acid diluted in
CH3OH. The solvents were evaporated, and the residue was
diluted in a mixture of CH3OH (5 mL) and 1 mL of an acetate
buffer (pH 5). The mixture was stirred at room temperature
in the presence of 10% palladium on charcoal (20 mg) and
under an atmosphere of hydrogen gas for 1 h. The catalyst
was removed by filtration and the solvent partially evaporated.
Resin Amberlite IR-120 (Na+ form, 2 mL) prewashed with
water was added to the mixture, and the resulting solution
was stirred for 12 h at room temperature. The residue was
filtered, the filtrate was concentrated, and the crude product
was purified on a Sephadex LH-20 column eluting with a
3,3′-O-(1,16-Hexa d eca m eth ylen e)-2,2′-d i-O-[(R)-3,7-d i-
m eth yloctyl]-1-O-(â-D-ga la ctofu r a n osyl)-1′-O-(â-la ctosyl)-
sn -d iglycer ol (7). Alcohol 36 (75 mg, 0.075 mmol) and lactosyl
thioglycoside 37 (65 mg, 0.096 mmol) were dissolved in CH2Cl2
(2 mL), and 4 Å molecular sieves (100 mg) were added. The
mixture was treated under nitrogen in the dark with N-
iodosuccinimide (22 mg, 0.096 mmol) followed by dropwise
addition of triethylsilyl trifluoromethanesulfonate (4 µL, 0.015
mmol). The reaction was quenched with a few drops of
triethylamine after 5 min at room temperature. The resulting
solution was diluted with CH2Cl2, washed successively with
10% aqueous sodium thiosulfate, water, and brine, dried over
MgSO4, and rotoevaporated. The crude product was purified
by silica gel chromatography with petroleum ether-EtOAc (11:
9) to give the acetylated diglycosylated lipid as a colorless oil
(85 mg, 70%), Rf ) 0.19 (solvent G); 1H NMR (400 MHz,
CDCl3) δ 0.82-0.89 (m, 18H), 1.08-1.40 and 1.45-1.60 (2m,