208
J. Lee et al. / Il Farmaco 56 (2001) 203–210
flash column chromatography over silica gel with hex-
ane/EtOAc (3:1) as eluant to afford 13 (0.286 g, 76%)
as an oil. 1H NMR (CDCl3): l 7.25–7.30 (m, 5H,
phenyl), 6.8–6.86 (m, 4H, Ar), 4.5–4.65 (m, 3H, H-2
and PhCH2O), 4.1 (m, 2H, CO2CH2), 3.9–4.02 (m, 2H,
ArCH2O), 3.76 (s, 3H, OCH3), 3.55–3.65 (m, 2H,
BnOCH2), 1.95–2.4 (m, 4H, H-3 and H-4), 1.26 (bs,
24H), 0.89 (distorted t, 3H, CH3); IR (neat) 1734 (CꢀO)
4.1.9. General procedure for the synthesis of 1–4
A solution of alcohol (14–17) (0.15 mmol), triethy-
lamine (0.06 ml, 0.60 mmol) and a catalytic amount of
dimethylamino pyridine in CH2Cl2 (10 ml) at 0°C was
treated with acyl chloride (0.30 mmol) dropwise. After
stirring for 2 h at r.t., the reaction mixture was
quenched with aqueous NaHCO3 solution and ex-
tracted with diethyl ether several times. The combined
organic layers were washed with water, brine and dried
over MgSO4. The filtrate was concentrated in vacuo
and the residue was purified by flash column chro-
matography over silica gel with hexane/EtOAc (3:1) as
eluant to afford the corresponding esters.
cm−1
.
4.1.7. (rel-2R,5S and rel-2S,5S) Methyl
5-[(benzyloxy)methyl]-5-(hydroxymethyl)
tetrahydro-2-furancarboxylate (14 and 16)
A mixture of above ester (0.1 mmol) and 10% Pd/C
(20 mg) in ethyl acetate (10 ml) was hydrogenated
under a balloon of hydrogen at r.t. for 1 h. The
reaction mixture was filtered through Celite with ethyl
acetate. The filtrate was concentrated in vacuo and the
residue was purified by flash column chromatography
over silica gel with hexane/EtOAc (3:1) as eluant to
afford 1–4.
A solution of 12 (0.142 g, 0.37 mmol) in acetonitrile
(9.2 ml) and water (2.3 ml) was cooled to 0°C, treated
with ammonium cerium nitrate (0.403 g, 0.74 mmol)
and stirred for 30 min. The reaction mixture was
quenched with aqueous NaHCO3 solution and ex-
tracted with diethyl ether several times. The combined
organic layers were washed with water, brine and dried
over MgSO4. The filtrate was concentrated in vacuo
and the residue was purified by flash column chro-
matography over silica gel with hexane/EtOAc (3:1) as
eluant to afford 14 (0.057 g, 56%) and 16 (0.035 g, 34%)
as oils, respectively.
4.1.10. (rel-2R,5R) Methyl 5-(hydroxymethyl)-5-
[(tetradecanoyloxy)methyl]tetrahydro-
2-furancarboxylate (1)
1
67% yield; a coloreless oil; H NMR (CDCl3): l 4.59
1
14: Rf: 0.4 (Hex:EtOAc=1:1); H NMR (CDCl3): l
(dd, 1H, J=5.7, 7.8 Hz, H-2), 4.34 (d, 1H, J=11.5 Hz,
CO2CH2), 4.17 (d, 1H, J=11.5 Hz, CO2CH2), 3.75 (s,
3H, CO2CH3), 3.54 (d, 1H, J=11.8 Hz, CH2OH), 3.48
(d, 1H, J=11.8 Hz, CH2OH), 2.34 (m, 3H, CH2CO2
and H-3a), 2.16 (m, 1H, H-3b), 2.01 (m, 1H, H-4a),
1.85 (m, 1H, H-4b), 1.60 (m, 2H, CH3(CH2)10-
CH2CH2CO2), 1.2–1.35 (m, 20H, CH3(CH2)10CH2CH2-
CO2), 0.88 (t, 3H, CH3(CH2)10CH2CH2CO2); IR (neat)
3456 (OH), 1739 (CꢀO) cm−1; MS (CI) m/z 401 (M+
+1); Anal. (C22H40O6) C, H.
7.25–7.35 (m, 5H, phenyl), 4.61 (dd, 1H, J=3.5 and
8.8 Hz, H–2), 4.53 (dd, 2H, PhCH2O), 3.78–3.80 (m,
4H, CO2CH3 and 1H of CH2OH), 3.56 (d, 1H, 1H of
CH2OH), 3.42 (s, 2H, BnOCH2), 1.94–2.44 (m, 4H,
H-3 and H-4); IR (neat) 3470 (OH), 1735 (CꢀO) cm−1
.
16: Rf: 0.2 (Hex:EtOAc=1:1); 1H NMR (CDCl3): l
7.25–7.35 (m, 5H, phenyl), 4.55–4.6 (m, 3H, H-2 and
PhCH2O), 3.76 (s, 3H, CO2CH3), 3.62 (m, 2H,
CH2OH), 3.42 (s, 2H, BnOCH2), 1.92–2.42 (m, 4H,
H-3 and H-4); IR (neat) 3470 (OH), 1735 (CꢀO) cm−1
.
4.1.11. (rel-2S,5R) Methyl 5-(hydroxymethyl)-5-
[(tetradecanoyloxy)methyl]tetrahydro-
2-furancarboxylate (2)
4.1.8. (rel-2R,5S and rel-2S,5S) Tetradecyl
5-[(benzyloxy)methyl]-5-(hydroxymethyl)
tetrahydro-2-furancarboxylate (15 and 17)
These compounds were prepared from 13 following
the same procedure for the synthesis of 14 and 16.
1
66% yield; a colorless oil; H NMR (CDCl3): l 4.59
(dd, 1H, J=5.7, 7.8 Hz, H-2), 4.34 (d, 1H, J=11.5 Hz,
CO2CH2), 4.17 (d, 1H, J=11.5 Hz, CO2CH2), 3.75 (s,
3H, CO2CH3), 3.54 (d, 1H, J=11.8 Hz, CH2OH), 3.48
(d, 1H, J=11.8 Hz, CH2OH), 2.34 (m, 3H, CH2CO2
and H-3a), 2.16 (m, 1H, H-3b), 2.01 (m, 1H, H-4a),
1.85 (m, 1H, H-4b), 1.60 (m, 2H, CH3(CH2)10-
CH2CH2CO2), 1.2–1.35 (m, 20H, CH3(CH2)10-
CH2CH2CO2), 0.88 (t, 3H, CH3(CH2)10CH2CH2CO2);
IR (neat) 3472 (OH), 1740 (CꢀO) cm−1; MS (CI) m/z
401 (M++1); Anal. (C22H40O6) C, H.
1
15: 42% yield, Rf: 0.7 (Hex:EtOAc=3:1); H NMR
(CDCl3): l 7.25–7.40 (m, 5H, phenyl), 4.5–4.6 (m, 3H,
H-2 and PhCH2O), 4.16 (t, 2H, CO2CH2), 3.66 (m, 2H,
CH2OH), 3.39 (s, 2H, BnOCH2), 1.9–2.45 (m, 4H, H-3
and H-4), 1.60 (m, 2H, CO2CH2CH2), 1.26 (bs, 22H),
0.88 (distorted t, 3H, CH3); IR (neat) 3470 (OH), 1736
(CꢀO) cm−1
.
1
17: 47% yield, Rf: 0.45 (Hex:EtOAc=3: 1); H NMR
(CDCl3): l 7.25–7.40 (m, 5H, phenyl), 4.5–4.63 (m,
3H, H-2 and PhCH2O), 4.15 (m, 2H, CO2CH2), 3.48–
3.70 (m, 4H, CH2OH and BnOCH2), 1.9–2.35 (m, 4H,
H-3 and H-4), 1.60 (m, 2H, CO2CH2CH2), 1.26 (bs,
22H), 0.88 (distorted t, 3H, CH3); IR (neat) 3470 (OH),
4.1.12. (rel-2R,5R) Tetradecyl 5-[(hexanoyloxy)-
methyl]-5-(hydroxymethyl)tetrahydro-2-
furancarboxylate (3)
1
56% yield; a colorless oil; H NMR (CDCl3): l 4.57
1736 (CꢀO) cm−1
.
(dd, 1H, J=5.4, 7.8 Hz, H-2), 4.36 (d, 1H, J=11.5 Hz,