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A. Kamal et al. / Tetrahedron: Asymmetry 16 (2005) 1855–1859
4.5. (R)-O-(4-Methoxyphenyl)-glycidol (R)-610a
(4H, m), 3.8 (3H, s), 4.0 (2H, d, J = 5.20 Hz), 4.2–4.5
(2H, m), 5.3–5.4 (1H, m), 6.8 (4H, s); LSIMS (m/z):
577 (M+ꢀ97), 552 (M+ꢀ122); Anal. Calcd for
C42H74O6: C, 74.51; H, 11.31. Found: C, 74.29; H, 11.13.
Prepared from (S)-5 (258 mg, 1 mmol), and 10% NaOH
(1 mL) following the same above procedure to get (R)-6
as a white solid; yield: 135 mg (75%); mp 42 ꢁC; 92% ee
[chiral HPLC analysis; DAICEL CHIRALCEL OD
(0.46 · 25 cm) column; eluent: hexane/isopropanol =
4.9. (S)-1,2-Dipalmitoyl-3-O-(40-methoxyphenyl)-sn-
glycerol (S)-8
90/10; flow rate: 0.7 mL/min; detector: 254 nm (tR =
25
D
13.11 min)]; ½aꢁ ¼ ꢀ10:8 (c 1.0, MeOH) {lit.10a
Prepared from (R)-7 following the same above proce-
dure to give (S)-8 as a white solid; yield: 270 mg
(89%); mp 64–65 ꢁC; 90% ee [chiral HPLC analysis;
DAICEL CHIRALCEL OD (0.46 · 25 cm) column;
eluent: hexane/isopropanol = 97.5/2.5; flow rate:
26
½aꢁ ¼ ꢀ11:7 (c 1.06, MeOH), 100% ee}.
D
4.6. (S)-3-O-(40-Methoxyphenyl)-sn-glycerol (S)-7
A suspension of ether (S)-6 (160 mg, 0.88 mmol) and CBr4
(28 mg, 0.086 mmol) in water (5 mL) was refluxed for 5–
6 h. After cooling, the reaction mixture was extracted with
ethyl acetate. The ethyl acetate layer was washed with
water to remove any excess of acid, dried and concen-
trated to give the crude diol, which after purification by
silica gel column chromatography (EtOAc-hexane, 6:4)
gave diol (S)-7 as a white crystalline solid; yield: 130 mg
(80%); mp 76–78 ꢁC; 97% ee [chiral HPLC analysis; DAI-
CEL CHIRALCEL AD-H (0.46 · 25 cm) column; eluent:
0.4 mL/min;
½aꢁ ¼ ꢀ10:7 (c 1.1, CHCl3).
detector:
254 nm
(tR = 6.87 min)];
25
D
4.10. (S)-1,2-Dipalmitoyl-sn-glycerol (S)-9
To a suspension of diester (S)-8 (190 mg, 0.28 mmol) in
acetonitrile–water 4:1 (4 mL) was added ceric ammo-
nium nitrate (360 mg, 0.67 mmol) at 0 ꢁC. The mixture
was stirred overnight at room temperature. Ethyl acetate
(50 mL) and brine (50 mL) were added and the organic
layer washed with saturated sodium hydrogen carbonate
solution (3 · 50 mL). The organic layer was dried over
anhydrous sodium sulfate and concentrated under re-
duced pressure. The crude compound obtained was puri-
fied by silica gel column chromatography (EtOAc-
hexane, 4:96) to give product (S)-9 as a white solid; yield:
150 mg (94%); mp 66–67 ꢁC [lit.14 mp 68–69 ꢁC]; 90% ee
hexane/isopropanol = 90/10; flow rate: 0.7 mL/min; detec-
25
D
tor: 254 nm (tR = 26.26 min)]; ½aꢁ ¼ þ7:9 (c 0.5, MeOH)
25
D
{lit.10a ½aꢁ ¼ þ7:8 (c 1.03, MeOH), 95% ee}; IR
(neat): 3425 cmꢀ1; H NMR (300 MHz, CDCl3): d 2.2
(1H, br s), 2.7 (1H, br s), 3.7 (1H, dd, J = 11.33,
5.28 Hz), 3.7 (3H, s), 3.8 (1H, dd, J = 11.33, 3.77 Hz)
3.9 (2H, d, J = 6.04 Hz), 4.0–4.2 (1H, m), 6.7 (4H, s);
LSIMS (m/z): 198 (M+), 125 (M+ꢀ73); Anal. Calcd for
C10H14O4: C, 60.6; H, 7.12. Found: C, 60.48; H, 7.09.
1
[determined from HPLC analysis of the precursor (S)-8
25
D
1
(tR = 6.87 min)]; ½aꢁ ¼ þ3:5 (c 1, CHCl3); IR (neat):
3400, 1730 cmꢀ1; H NMR (200 MHz, CDCl3): d 0.9
(6H, m), 1.3 (48H, br s), 1.6 (4H, br s), 2.3–2.4 (4H,
m), 3.7 (2H, t, J = 5.66 Hz), 4.3 (2H, dd, J = 12.08,
4.53 Hz), 4.9–5.1 (1H, m); FABMS (m/z): 552
(M+ꢀ16); Anal. Calcd for C35H68O5: C, 73.63; H,
12.36. Found: C, 73.29; H, 12.34.
4.7. (R)-3-O-(40-Methoxyphenyl)-sn-glycerol (R)-7
Prepared from (R)-6 (160 mg, 0.88 mmol) and CBr4
(0.028 g, 0.086 mmol) following the same above proce-
dure to give (R)-7 as a white crystalline solid; yield:
130 mg (80%); mp 76–77 ꢁC; 90% ee [chiral HPLC anal-
ysis; DAICEL CHIRALCEL AD-H (0.46 · 25 cm)
column; eluent: hexane/isopropanol = 90/10; flow rate:
0.7 mL/min; detector: 254 nm (tR = 22.77 min)];
4.11. (R)-1,2-Dipalmitoyl-sn-glycerol (R)-9
Prepared from (R)-8 following the same above proce-
dure to give (R)-9 as a white solid; yield: 150 mg
25
25
D
½aꢁ ¼ ꢀ7:4 (c 0.5, MeOH) {lit.10a ½aꢁ ¼ ꢀ8:25 (c
D
1.15, MeOH), 100% ee}.
(94%); mp 67 ꢁC; 97% ee [determined from HPLC analy-
25
D
sis of the precursor (R)-8 (tR = 7.65 min)]; ½aꢁ ¼ ꢀ2:7
25
D
4.8. (R)-1,2-Dipalmitoyl-3-O-(40-methoxyphenyl)-sn-
glycerol (R)-8
(c 1, CHCl3) {lit.6b ½aꢁ ¼ ꢀ2:7 (c 3.9, CHCl3), 95% ee}.
To a solution of diol (S)-7 (90 mg, 0.45 mmol) in dichlo-
romethane (7 mL) were added DMAP (120 mg,
0.98 mmol), palmitic acid (250 mg, 0.98 mmol) and
DCC (400 mg, 1.98 mmol). The reaction mixture was
stirred at room temperature for 60 h, filtered and evap-
orated to give the crude product, which on purification
by column chromatography (CHCl3-hexane, 4:6) gave
product 8 as a white solid; yield: 260 mg (85%); mp
64–65 ꢁC; 97% ee [chiral HPLC analysis; DAICEL CHI-
RALCEL AD-H (0.46 · 25 cm) column; eluent: hexane/
Acknowledgements
We are thankful to the Department of Science and Tech-
nology, New Delhi, for the financial assistance for
Grants-in-Aid project under SERC (No. SR/S1/OC-36/
2003). Three of the authors MS, AAS and MSM are
thankful to CSIR, New Delhi, for the award of research
fellowship.
isopropanol = 97.5/2.5; flow rate: 0.4 mL/min; detec-
References
25
D
tor: 254 nm (tR = 7.65 min)]; ½aꢁ ¼ þ11:5 (c 1, CHCl3)
25
{lit.6b ½aꢁ ¼ þ11:3 (c 6.8, CHCl3), 95% ee}; IR
1. (a) Walsh, J. P.; Fahrner, L.; Bell, R. M. J. Biol. Chem.
1990, 265, 4374; (b) Ganong, B. R.; Loomis, C. R.;
Hannun, Y. A.; Bell, R. M. Proc. Natl. Acad. Sci. U.S.A.
D
(neat): 1730 cmꢀ1
0.8–1.0 (6H, m), 1.3 (48H, br s), 1.6 (4H, br s), 2.3–2.4
;
1H NMR (200 MHz, CDCl3): d