T. Yamamoto et al. / Bioorg. Med. Chem. 15 (2007) 1346–1355
1353
to ꢀ20 °C and stirred for 30 min. After cooling to
phenyl benzenethiosulfonate (7.18 g,
56.40; H, 8.22. 30b: IR (neat): 2998, 1744 cmꢀ1
;
1H
ꢀ78 °C,
NMR (CDCl3): d 6.53 (t, 1H, J = 6.6 Hz), 5.87 (s,
1H), 4.24 (q, 2H, J = 7.1 Hz), 4.20 (q, 2H, J = 7.2 Hz),
3.73 (t, 2H, J = 6.3 Hz), 2.81 (q, 2H, J = 6.3 Hz), 1.30
(t, 3H, J = 7.1 Hz), 1.26 (t, 3H, J = 7.1 Hz), 0.89 (s,
9H), 0.05 (s, 6H); 13C NMR (CDCl3): d 172.8, 165.8,
144.1, 131.3, 66.7, 61.9, 61.5, 60.9, 32.0, 25.9, 14.1,
ꢀ5.4. Anal. Calcd for C19H34O7Si: C, 56.40; H, 8.51.
Found: C, 56.40; H, 8.22.
28.7 mmol) was added, and the reaction mixture was
warmed to 0 °C. After 5 min, acetic acid (6.0 ml) was
added. After warmed to room temperature, the reaction
mixture was poured into aqueous NH4Cl (70 ml) and the
mixture was extracted with diethyl ether (four times).
The combined organic layer was washed with saturated
NaHCO3 and brine, and dried over MgSO4. After evap-
oration of the solvent, the residue was purified by flash
column chromatography with hexane–ethyl acetate (92/
8) to give a mixture (1:1) of two diastereoisomers
(3.25 g, 31%). To a solution of the product (3.20 g,
3.2.16. (R,E)-(3-Hydroxypropylidene)malic Acid (27a).
A mixture of 30a (112 mg, 0.299 mmol) and 2 M HCl
(1.2 ml) was stirred for 20 h at 50 °C. The solvent was
evaporated and the crude product was chromato-
graphed over silica gel (Merck silica gel 60-silanized,
water) to give 27a (51 mg, 90%): IR (KBr): 3570,
6.80 mmol),
4-(dimethylamino)pyridine
(166 mg,
1.36 mmol), and triethylamine (1.91 ml, 13.6 mmol) in
CH2Cl2 (6.8 ml) was added acetic anhydride (0.95 ml,
10.2 mmol) at 0 °C. After 30 min at room temperature,
the reaction was quenched by addition of water. The
mixture was extracted with ethyl acetate (four times),
and the combined organic layer was washed with brine,
dried over MgSO4, filtered, and evaporated. The crude
was chromatographed over silica gel with hexane–ethyl
acetate (95/5) to afford a mixture of two diastereoisomers
of 29 (3.18 g, 91%): IR (neat): 2983, 1747, 1643 cmꢀ1; 1H
NMR (CDCl3): d 7.66–7.62 (m, 1H), 7.66–7.62 (m, 1H),
7.54–7.51 (m, 1H), 7.54–7.51 (m, 1H), 7.37–7.25 (m, 3H),
7.37–7.25 (m, 3H), 5.74 (s, 1H), 5.62 (s, 1H), 4.33–3.95
(m, 4H), 4.33–3.95 (m, 4H), 3.62–3.58 (m, 2H), 3.62–
3.58 (m, 2H), 2.14 (s, 3H), 2.03–1.78 (m, 2H), 2.03–1.78
(m, 2H), 1.86 (s, 3H), 1.32 (t, 3H, J = 7.1 Hz), 1.24 (t,
3H, J = 7.1 Hz), 1.23 (t, 3H, J = 7.1 Hz), 1.13 (t, 3H,
J = 7.1 Hz), 0.89 (s, 9H), 0.88 (s, 9H), 0.05 (s, 6H), 0.04
(s, 6H); 13C NMR (CDCl3): d 173.1, 173.0, 171.4,
170.9, 137.2, 137.2, 130.5, 130.3, 130.1, 129.9, 128.8,
128.5, 77.4, 77.3, 65.4, 64.3, 62.9, 62.7, 62.3, 62.3, 61.1,
61.0, 45.4, 46.1 30.0, 28.7, 27.5, 27.5, 20.2, 20.2, 18.4,
18.4, 14.0, 13.9, 13.7, 13.7, ꢀ5.5, ꢀ5.5. Anal. Calcd for
C25H40O7SSi: C, 58.56; H, 7.86; S, 6.25. Found: C,
58.53; H, 7.61; S, 6.51.
1
1798 cmꢀ1; H NMR (D2O): d 7.00 (t, 1H, J = 7.6 Hz),
4.90 (s, 1H), 3.55 (t, 2H, J = 6.4 Hz), 2.41 (q, 2H,
J = 6.4 Hz); 13C NMR (D2O): d 174.4, 170.4, 144.2,
135.2, 66.3, 60.1, 38.9. Anal. Calcd for C7H10O6: C,
44.21; H, 5.30. Found: C, 43.97; H, 5.56.
3.2.17. (R,Z)-(3-Hydroxypropylidene)malate (27b). Com-
pound 27b was synthesized by the similar procedure de-
scribed for the preparation of 27a (60% yield): IR
(KBr): 3476, 1772 cmꢀ1; 1H NMR (D2O): d 6.31 (t, 1H,
J = 7.6 Hz), 4.78 (s, 1H), 3.55 (t, 2H, J = 6.4 Hz), 2.59
(q, 2H, J = 6.4 Hz); 13C NMR (D2O): d 176.9, 169.5,
147.2, 132.2, 66.3, 60.6, 31.8. Anal. Calcd for C7H8Li2O6:
C, 41.62; H, 3.99. Found: C, 41.20; H, 4.28.
3.2.18. Diethyl (2R)-2-O-acetyl-3-{3-(t-butyldimethylsil-
oxy)butyl}-3- (phenylthio)malate (31). Compound 31 was
synthesized by the similar procedure described for the
preparation of 29 (37% yield). IR (neat): 2980,
1760 cmꢀ1 1H NMR (CDCl3): d 7.64–7.62 (m, 1H),
;
7.64–7.62 (m, 1H), 7.53–7.51 (m, 1H), 7.53–7.51 (m,
1H), 7.37–7.25 (m, 3H), 7.37–7.25 (m, 3H), 5.71 (s,
1H), 5.61 (s, 1H), 4.33–4.09 (m, 4H), 4.33–4.09 (m,
4H), 3.63–3.58 (m, 2H), 3.63–3.58 (m, 2H), 2.13 (s,
3H), 1.98–1.78 (m, 4H), 1.98–1.78 (m, 4H), 1.86 (s,
3H), 1.51–1.48 (2H, m), 1.51–1.48 (2H, m) 1.32 (t, 3H,
J = 7.1 Hz), 1.24 (t, 3H, J = 7.1 Hz), 1.23 (t, 3H,
J = 7.1 Hz), 1.14 (t, 3H, J = 7.1 Hz), 0.89 (s, 9H), 0.88
(s, 9H), 0.05 (s, 6H), 0.04 (s, 6H); 13C NMR (CDCl3):
d 169.6, 169.4, 169.4, 169.3, 130.1, 129.8, 129.6, 129.5,
128.5, 128.3, 76.6, 74.2, 62.8, 62.0, 61.9, 61.9, 61.8,
61.5, 60.8, 33.9, 33.5, 33.4, 26.0, 26.0, 21.3, 21.0, 20.6,
20.3, 14.3, 14.2, 14.1, 14.1, ꢀ5.2, ꢀ5.2. Anal. Calcd for
C26H42O7SSi: C, 59.28; H, 8.04; S, 6.09. Found: C,
59.48; H, 8.19; S, 6.30.
3.2.15. Diethyl (R,E and R,Z)-2-O-acetyl-3-{3-(t-butyl-
dimethylsiloxy)propylidene}malate (30a and 30b). To a
solution of 29 (396 mg, 0.770 mmol) in CH2Cl2
(3.1 ml) was added m-CPBA (214 mg, 0.71 mmol) at
0 °C. After stirring for 30 min, the reaction was
quenched with aq Na2S2O3. The mixture was neutral-
ized by addition of aq NaHCO3 and then the layers were
separated. The aqueous layer was extracted with ethyl
acetate (four times), and the combined organic layer
was washed with brine, dried over MgSO4, filtered,
and concentrated in vacuo. The residue was dissolved
in toluene (30 ml) and the solution was warmed to
80 °C. After 5 h, the solution was evaporated and the
residue was purified by flash silica gel chromatography
with hexane–ethyl acetate (80/20) to afford 30a
(170 mg, 55%) and 30b (114 mg, 37%): 30a: IR (neat):
3.2.19. Diethyl (2R)-2-O-acetyl-3-{3-methoxycarbonyl-
propyl}-3-(phenylthio)malate (32). To a solution of 31
(1.26 g, 2.52 mmol) in ethanol (25 ml) was added pyri-
dinium p-toluenesulfonate (256 mg, 1.00 mmol) at room
temperature. After 10 h at room temperature, the reac-
tion was quenched by addition of NaCO3 aq at 0 °C.
The mixture was extracted with ethyl acetate (four
times). The combined organic layer was washed with
brine, dried over MgSO4, filtered, and evaporated. The
residue was chromatographed over silica gel with hex-
ane–ethyl acetate (70/30) to afford a mixture (1:1) of
2970, 1747 cmꢀ1 1H NMR (CDCl3): d 7.21 (t, 1H,
;
J = 7.4 Hz), 6.21 (s, 1H), 4.27–4.16 (m, 4H), 3.74 (t,
2H, J = 6.4 Hz), 2.66–2.50 (m, 2H), 1.29 (t, 3H,
J = 7.1 Hz), 1.25 (t, 3H, J = 7.1 Hz), 0.89 (s, 9H), 0.05
(s, 6H); 13C NMR (CDCl3): d 170.0, 168.6, 143.3,
131.7, 62.2, 62.0, 61.8, 54.9, 32.0, 25.1, 14.1, ꢀ5.0. Anal.
Calcd for C19H34O7Si: C, 56.91; H, 8.51, Found: C,