Roy et al.
(m, 2H), 3.63-3.69 (m, 2H), 3.73-3.77 (m, 2H), 3.92-3.98 (m,
2H), 4.43-4.38 (m, 2H), 4.40-4.42 (m, 1H), 7.90 (s, 2H). Anal.
Calcd for C50H88N4O10: C, 66.34; H, 9.80; N, 6.19. Found: C,
66.15; H, 9.68; N, 6.06.
Compound 14: Compound 4 (1.39 g, 3.51 mmol) was
dissolved in absolute ethanol (50 mL) and NaBH4 (0.40 g, 10.25
mmol) was added. After hydrogen evolution ceased, CaCl2 (1.16
g, 10.45 mmol) was added batch- wise with stirring. Stirring
was continued for 3 h and reaction was quenched with water.
Solvent was evaporated under reduced pressure and the white
solid was triturated with CH2Cl2. The combined CH2Cl2 layer
was removed under reduced pressure. Yield: 0.95 g (86%). 1H
NMR (400 MHz, CDCl3-D2O) δ 3.38 (t, 2H, J ) 5.0 Hz), 3.64-
3.74 (m, 6H), 3.87 (t, 2H, 5.0 Hz), 4.18 (t, 2H, J ) 5.01 Hz),
4.66 (s, 4H), 6.73 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 50.87,
64.41, 67.71, 69.58, 70.30, 70. 90, 71.07, 105.76, 160.77, 166.46.
To a solution of the above alcohol (0.89 g, 2.25 mmol) in CH2-
Cl2 (20 mL) was added PBr3 (1.22 g, 4.51 mmol). The resulting
solution was refluxed with stirring for 18 h. The solution was
neutralized with an aqueous solution of NaHCO3 (5%) in ice
cold condition. The organic solvent was washed with water and
was dried on anhydrous Na2SO4. Yield: 1.1 g (88%). 1H NMR
(300 MHz, CDCl3) δ 3.43 (t, 2H, J ) 5.0 Hz), 3.70-3.97 (m,
6H), 3.91-3.95 (m, 2H), 4.26 (t, 2H, J ) 4.5 Hz), 4.52 (s, 4H),
6.96 (s, 2H).
Lipid 11: The coupling of acid 9 (0.46 g, 0.545 mmol) and
amine 5 (0.225 g, 0.545 mmol) was achieved in the presence
of BOP (0. 245 g, 0.545 mmol) and Et3N (0.3 mL, 2.15 mmol)
in CH2Cl2 (25 mL). The reaction was carried out for 10 h at
room temperature. The work-up procedure was the same as
mentioned for 9 ester. The lipid was precipitated from water,
filtered, and washed with water to afforded lipid ester as a
1
white solid (0.61 g, 95%). H NMR (300 MHz, CDCl3) δ 0.88
(t, 6H, J ) 7.1 Hz), 1.25-1.39 (m, 50H), 1.42-1.67 (m, 18H),
1.70-1.79 (m, 1H), 1.89-2.05 (m, 1H), 2.10-2.28 (m, 16H),
3.35-3.48 (m, 4H), 3.49-3.56 (m, 2H), 3.59-3.67 (m, 2H),
3.69-3.73 (m, 2H), 3.88-3.94 (m, 2H), 4.29-4.37 (m, 2H),
4.42-4.55 (m, 5H), 5.94 (br s, 1H), 6.49 (d, 1H, J ) 8.0 Hz),
6.87 (br s, 1H), 7.82 (s, 2H). 13C NMR (125 MHz, CDCl3) δ
14.29, 14.42, 18.64, 19.43, 22.90, 25.81, 25.94, 26.10, 28.57,
28.62, 28.67, 28.89, 29.02, 29.10, 29.15, 29.17, 29.32, 29.37,
29.40, 29.46, 29.51, 29.56, 29.70, 29.82, 29.85, 29.87, 30.68,
32.14, 36.77, 36.98, 38.71, 39.45, 52.19, 62.64, 65.53, 65.67,
68.52, 69.44, 69.91, 70.50, 71.16, 77.65, 77.85, 114.69, 150.33,
165.09, 166.99, 172.11, 173.57, 174.15.
Compound 15: Dibromo compound 14 (0.71 g, 1.62 mmol)
and diethyliminodiacetate (0.62 g, 3.28 mmol) were dissolved
in CH3CN and anhydrous K2CO3 (1.8 g, 12.9 mmol) was added.
The mixture was refluxed for 15 h. The solid was filtered and
solvent was removed under vacuo. The crude product was
purified by silica gel column chromatography with 10% MeOH
in CHCl3 (Rf 0.4) to afford a yellowish viscous liquid. Yield:
The polymerizable lipid ester (0.5 g, 0.418 mmol) was
dissolved in CH2Cl2/THF/MeOH (4/2/6 mL) and solid LiOH‚
H2O (61 mg, 1.45 mmol) was added. It resulting mixture was
stirred at room temperature for 12 h. The work-up procedure
was the same as described for lipid 10. Yield: 0.385 g (81%).
1
1.03 g (97%). H NMR (400 MHz, CDCl3) δ 1.27 (t, 12H, J )
25
1
7.1 Hz), 3.41 (t, 2H, J ) 4.9 Hz), 3.49 (t, 2H, J ) 4.9 Hz), 3.60
(s, 8H), 3.69-3.72 (m, 4H), 3.73-3.76 (m, 2H), 3.88 (t, 2H, J
) 4.8 Hz), 3.99 (s, 4H), 4.14-4.21 (m, 8H), 7.10 (s, 2H). 13C
NMR (100 MHz, CDCl3) δ 33.81, 50.87, 67.89, 69.54, 70.33,
70.92, 71.14, 109.64, 158.34, 166.64, 171.21.
[R]
-3.4° (c 0.5, CHCl3). H NMR (300 MHz, CDCl3-CD3-
D
OD-D2O) δ 0.92 (t, 6H, J ) 7.1 Hz), 1.27-1.47 (m, 48H), 1.47-
1.56 (m, 8H), 1.58-1.67 (m 7H), 1.72-1.80 (m, 1H), 2.13-2.21
(m, 4H), 2.24-2.30 (m, 12H), 3.14-3.25 (m, 2H), 3.35-3.42
(m, 2H), 3.52-3.58 (m, 2H), 3.63-3.68 (m, 2H), 3.70-3.76 (m,
2H), 3.92-3.98 (m, 2H), 4.30-4.4.35 (m, 1H), 4.42-4.49 (m,
2H), 7.91 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 14.40, 18.65,
19.50, 22.98, 25.81, 25.97, 26.13, 28.67, 28.96, 29.11, 29.16,
29.25, 29.39, 29.47, 29.64, 29.77, 29.91, 29.94, 29.98, 32.21,
36.80, 36.90, 39.26, 39.70, 52.73, 65.54, 65.61, 68.51, 69.13,
69.93, 70.55, 71.21, 77.64, 77.71, 114.39, 148.62, 165.31,
168.83, 172.45, 174.37, 174.97. Anal. Calcd for C68H108N4O10‚
H2O: C, 70.36; H, 9.48; N, 4.82. Found: C, 70.85; H, 9.53; N,
4.61.
To a solution of the above azide-ester (0.66 g, 1.01 mmol)
was added a small portion of Pd-black and the solution was
stirred at room temperature for 20 h while H2 gas was bubbled
through (the completion of the reaction was confirmed by TLC).
The Pd-black was filtered off and solvent was removed to afford
compound 15 as a viscous oil. Yield: 0.625 g (98%).1H NMR
(300 MHz, CDCl3-D2O) δ 1.29 (t, 12H, J ) 7.1 Hz), 3.46-
3.50 (m, 2H), 3.59-3.64 (m, 10H), 3.71-3.76 (m, 6H), 3.86-
3.89 (m, 2H), 4.00 (s, 4H), 4.18 (q, 8H, J ) 7.1 Hz), 7.11 (s,
2H). 13C NMR (100 MHz, CDCl3) δ 55.09, 60.13, 60.72, 67.52,
69.60, 70.64, 71.01, 107.87, 160.33, 166.54, 171.40, 171.53.
Lipid 17: The coupling of nonpolymerizable acid 13 (0.2 g,
0.425 mmol) with amine 15 (0.35 g, 0.55 mmol) was carried
out in the presence of BOP (0.19 g, 0.43 mmol) and Et3N (0.2
mL, 1.43 mmol) in CHCl3. The work-up procedure was the
same as mentioned for lipid 9 (ester). The crude product was
purified by silica gel column chromatography with 8% MeOH
in CHCl3. Yield: 0.43 g (72%). 1H NMR (500 MHz, DMSO-d6)
δ 0.90-0.95 (m, 6H), 1.22-1.26 (m, 12H), 1.28-1.39 (m, 48H),
1.49-1.58 (m, 4H), 2.09 (t, 2H, J ) 7.7 Hz), 2.15 (t, 2H, J )
7.5 Hz), 3.57-3.62 (m, 12H), 3.64-3.69 (m, 6H), 3.89-3.85 (m,
4H), 3.91 (s, 4H), 4.13 (q, 8H, J ) 7.1 Hz), 4.19-4.24 (m, 1H),
7.05 (s, 2H), 7.71 (br s, 1H), 7.75 (br s, 1H), 7.95 (br s, 1H).
The above ester (0.26 g, 0.24 mmol) was dissolved in CH2-
Cl2-THF-MeOH (2/2/4 mL) and solid LiOH (60 mg, 1.43
mmol) was added. The mixture was then stirred at room
temperature for 15 h. The work-up procedure was the same
as described for lipid 8. Yield: 0.19 g (71%). 1H NMR (500
MHz, DMSO-d6) δ 0.86-0.90 (m, 6H), 1.20-1.32 (m, 48H),
1.44-1.52 (m, 4H), 2.03-2.08 (m, 2H), 2.10-2.14 (m, 2H),
3.19-3.32 (m, 8H), 3.45 (s, 8H), 3.51-3.55 (m, 2H), 3.59-3.64
(m, 2H), 3.75-3.78 (m, 2H), 3.91 (s, 4H), 4.13-4.19 (m, 1H),
7.00 (s, 2H), 7.69 (br s, 2H), 7.78 (br s, 1H). Anal. Calcd for
C56H98N6O14: C, 62.31; H, 9.15; N, 7.79. Found: C, 62.65; H,
9.30; N, 7.52.
Lipid 11‚Eu3+ complex: The polymerizable acid 11 (50 mg,
0.043 mmol) was dissolved in CHCl3/MeOH (2/2 mL) and solid
EuCl3 (17 mg, 0.043 mmol) was added with stirring at room
temperature for 30 h. The solvent was removed under vacuo
to afford a white solid as the Eu3+complex. Yield: 55 mg (98%).
Anal. Calcd for C68H112N4O13EuCl‚3H2O: C, 58.96; H, 8.17; N,
4.06. Found: C, 59.14; H, 7.98; N, 3.68.
Compound 13: The racemic 2,3-diaminopropanoic ester
(5.0 g, 10.82 mmol) was suspended in dry CH2Cl2 (60 mL),
followed by the addition of DMAP (50 mg, 0.41 mmol) and Et3N
(8.5 mL, 61.1 mmol). The resulting solution was cooled to 5
°C, then palmitoyl chloride (5.8 g, 21.0 mmol) was added
dropwise. Stirring was continued for another 8 h at room
temperature. The reaction was quenched with ice cold water
(80 mL). The organic solvent was removed under vacuo and
white solid precipitated out. The precipitate was then filtered
1
and washed with water successively. Yield: 6.37 g (99%). H
NMR (500 MHz, CDCl3) δ 0.86 (t, 6H, J ) 7.1 Hz), 1.19-1.33
(m, 48H), 1.56-1.63 (m, 4H), 2.16 (t, 2H, J ) 7.7 Hz), 2.22 (t,
2H, J ) 7.7 Hz), 3.61-3.64 (m, 2H), 3.75 (s, 3H), 4.57-4.61
(m, 1H), 6.15 (t, 1H, J ) 5.8 Hz), 6.8 (d, 1H, J ) 5.3 Hz). 13C
NMR (125 MHz, CDCl3) δ 14.35, 22.92, 25.77, 29.48, 29.61,
29.63, 29.75, 29.88, 29.90, 29.94, 32.16, 32.69, 36.81, 41.87,
52.98, 53.73, 171.00, 174.15, 174.99.
The ester (2.0 g, 3.36 mmol) was hydrolyzed with LiOH
(0.215 g, 5.12 mmol) in CH2Cl2-THF-MeOH (10/10/20 mL).
The work-up procedure was the same as described for lipid 8.
Lipid 18: Polymerizable acid 1613 (0.31 g, 0.38 mmol) was
coupled with amine 15 (0.33 g, 0.525 mmol) in the presence of
BOP reagent (0.17 g, 0.38 mmol) and Et3N (0.1 mL, 0.72 mmol)
in CHCl3. The rest of the procedure was the same as mentioned
for lipid 9 (ester). The crude product was purified by silica gel
1
Yeild: 1.92 g (98%). H NMR (400 MHz, DMSO-d6) δ 0.86 (t,
6H, J ) 7.1 Hz), 1.16-1.32 (m, 48H), 1.47-1.58 (m, 4H), 2.09
(t, 2H, J ) 7.5 Hz), 2.14 (t, 2H, J ) 7.5 Hz), 3.43-3.53 (m,
2H), 4.32-4.41 (m, 1H), 7.64 (br s, 1H), 7.72 (br s, 1H).
4006 J. Org. Chem., Vol. 68, No. 10, 2003