M. Asai et al. / Tetrahedron 57 .2001) 4543±4558
4555
MeOH &18 mL), and CH&OMe)3 &9 mL) and DL-CSA
&200 mg, 0.855 mmol) were added. After stirring at rt for
10h, the mixture was quenched with sat. NaHCO 3 solution
and extracted with AcOEt &£3). The combined organic layer
was washed with brine &£1) and dried over anhydrous
Na2SO4. The solution was concentrated under reduced
pressure, and the residue was puri®ed by column chroma-
tography &silica gel 50g, ether/hexane 5:1) to give
dimethylacetal 35 &772 mg, 78%, 2 steps from 6) as a color-
37 &1.35 g) was used for the next reaction without puri®-
cation. A portion of this material was puri®ed by column
chromatography ðer/hexane5:1!ether only). IR &KBr)
max 3416, 2939, 1743, 1684, 1545, 1373, 1244, 1166 cm21
.
n
1H NMR &300 MHz, CDCl3) d 1.41 &1H, dd, J16.5, 14 Hz,
Me±C±CHaxHeq), 1.58 &3H, s, CH3), 2.05 &3H, s, OAc), 2.20
&3H, s, OAc), 2.38 &1H, ddd, J16.5, 4.5, 2 Hz, Me±C±
CHaxHeq), 3.21 &3H, s, OCH3), 3.25 &3H, s, OCH3), 3.38
&1H, ddd, J14, 7, 4.5 Hz, ±CH±), 4.25 &1H, dd, J15,
6 Hz, NH±CHAHB±Ph), 4.38 &1H, dd, J15, 6 Hz, NH±
CHAHB±Ph), 4.61 &1H, d, J7 Hz, CH&OMe)2), 4.66 &2H,
s, O±CH2±Ph), 4.76 &1H, br t, J6 Hz, NH±CH2±Ph), 4.82
&1H, br s, C±NH±CO), 5.04 &1H, t, J2 Hz, BnO±CH±
CH), 5.16 &1H, d, J2 Hz, BnO±CH), 5.87 &1H, s, CH±
OAc), 7.24±7.34 &10H, m, aromatic). 13C NMR &75 MHz,
CDCl3) d 20.8, 21.6, 22.0, 30.9, 37.5, 44.0, 51.8, 53.2, 60.6,
70.3, 72.5, 72.8, 79.9, 80.7, 103.7, 127.3, 127.9, 128.1,
128.4, 128.6, 137.4, 139.1, 157.0, 166.8, 170.0, 171.0. MS
&FAB) m/z 599 &M1H), 567 &M±OMe).
27
less amorphous solid. [a]D 2458 &c 0.92, CHCl3). IR &KBr)
n
max 3477, 3358, 2935, 1745, 1718, 1535, 1375, 1217, 1167,
1
1081 cm21. H NMR &300 MHz, CDCl3) d 1.38 &3H, s,
CH3), 1.46 &1H, dd, J16, 13 Hz, Me±C±CHaxHeq), 1.89
&1H, ddd, J16, 4.5, 2 Hz, Me±C±CHaxHeq), 2.28 &3H, s,
OAc), 3.24 &3H, s, OCH3), 3.26 &3H, s, OCH3), 3.47 &1H,
ddd, J13, 8.5, 4.5 Hz, ±CH±), 4.24 &1H, t, J2 Hz, BnO±
CH±CH), 4.63 &1H, d, J8.5 Hz, CH&OMe)2), 4.64 &1H, d,
J11.5 Hz, CHAHB±Ph), 4.73 &1H, d, J11.5 Hz, CHAHB±
Ph), 5.35 &1H, d, J2 Hz, BnO±CH), 5.93 &1H, s, CH±
OAc), 7.26±7.35 &5H, m, aromatic), 7.65 &1H, br s, NH).
13C NMR &75 MHz, CDCl3) d 20.7, 26.8, 33.5, 36.2, 50.2,
54.1, 63.0, 70.1, 70.9, 72.5, 73.1, 82.4, 92.6, 104.0, 128.0,
128.1, 128.5, 137.2, 160.7, 166.0, 171.4. MS &FAB) m/z 536
&M±OMe), 538 &M±OMe), 540&M±OMe). Anal. calcd for
C23H28O9NCl3: C, 48.56; H, 4.96; N, 2.46. Found C, 48.56;
H, 4.82; N, 2.55.
4.1.24. Methylacetal 38. To a solution of the crude benzyl-
urea 37 &1.35 g) in EtOH &40mL) was added KCN &13 mg,
0.204 mmol). After stirring at rt for 1 h, the mixture was
diluted with sat. NaHCO3 solution, and extracted with
AcOEt &£3). The combined organic layer was dried over
anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was dissolved in acetone &40mL)
and DL-CSA &47 mg, 0.204 mmol) was added. After stirring
at rt for 2 h, the reaction mixture was quenched with sat.
NaHCO3 solution, and the mixture was extracted with
CH2Cl2 &£3). The combined organic layer was dried over
anhydrous Na2SO4, and concentrated under reduced pres-
sure. The residue was puri®ed by column chromatography
&silica gel 80g, ether/hexane 1:1!3:1!5:1) to give
methylacetal 38 &618 mg, 58%, 3 steps from 36) and its
4.1.22. Diacetate 36. To a solution of the dimethylacetal 35
&489 mg, 0.839 mmol) in pyridine &7 mL) and acetic anhy-
dride &7 mL) was added DMAP &5 mg). After stirring at rt
for 24 h, the reaction mixture was diluted with toluene
&20mL), and concentrated in vacuo. The residue was
puri®ed by column chromatography &silica gel 25 g, ether/
hexane3:1!5:1) to give diacetate 36 &528 mg, 100%). Mp
109±1108C &as colorless needles from ether±hexane).
27
[a]D 2248 &c 0.89, CHCl3). IR &KBr) nmax 3402, 2939,
C-4 epimer &133 mg, 12%, 3 steps from 36). 38. Mp 184±
1
26
1779, 1750, 1727, 1527, 1373, 1222, 1173, 1094 cm21. H
1858C &as white tiny needles from ether±hexane). [a]D
NMR &400 MHz, CDCl3) d 1.41 &1H, dd, J16, 13 Hz,
Me±C±CHaxHeq), 1.61 &3H, s, CH3), 2.01 &3H, s, OAc),
2.29 &3H, s, OAc), 2.48 &1H, ddd, J16, 4.5, 2 Hz, Me±
C±CHaxHeq), 3.21 &3H, s, OCH3), 3.25 &3H, s, OCH3),
3.38 &1H, ddd, J13, 8, 4.5 Hz, ±CH±), 4.63 &1H, d, J
11.5 Hz, CHAHB±Ph), 4.64 &1H, d, J8 Hz, CH&OMe)2),
4.68 &1H, d, J11.5 Hz, CHAHB±Ph), 5.03 &1H, t, J
2 Hz, BnO±CH±CH), 5.06 &1H, d, J2 Hz, BnO±CH),
5.95 &1H, s, CH±OAc), 7.29±7.38 &5H, m, aromatic), 7.69
&1H, br s, NH). 13C NMR &75 MHz, CDCl3) d 20.7, 21.6,
21.9, 31.0, 35.5, 49.7, 54.0, 62.6, 69.9, 71.1, 73.0, 79.0,
80.3, 92.6, 103.5, 128.3, 128.4, 128.6, 136.5, 160.9, 165.7,
169.8, 171.4. MS &FAB) m/z 578 &M±OMe), 580&M±
OMe), 582 &M±OMe). Anal. calcd for C25H30O10NCl3: C,
49.15; H, 4.95; N, 2.29. Found C, 49.24; H, 4.97; N, 2.31.
21088 &c 0.41, CHCl3). IR &KBr) nmax 3394, 2908, 1754,
1736, 1646, 1552, 1237 cm21. 1H NMR &400 MHz, CDCl3)
d 1.60&3H, s, C H3), 1.64 &1H, dd, J16.5, 11.5 Hz, Me±C±
CHaxHeq), 2.06 &3H, s, OAc), 2.18 &1H, ddd, J16.5, 8,
1 Hz, Me±C±CHaxHeq), 3.42 &1H, ddd, J11.5, 8, 4 Hz,
±CH±), 3.44 &3H, s, OCH3), 4.11 &1H, s, MeO±CH±O±
CH), 4.27 &1H, dd, J15, 6 Hz, NH±CHAHB±Ph), 4.32
&1H, dd, J15, 6 Hz, NH±CHAHB±Ph), 4.42 &1H, d, J
11.5 Hz, O±CHAHB±Ph), 4.60&1H, d,
J11.5 Hz,
O±CHAHB±Ph), 4.80&1H, d, J2 Hz, BnO±CH), 4.84
&1H, br s, C±NH±CO), 5.02 &1H, br t, J6 Hz, NH±
CH2±Ph), 5.19 &1H, dd, J2, 1 Hz, BnO±CH±CH), 5.26
&1H, d, J4 Hz, CH±OMe), 7.19±7.34 &10H, m, aromatic).
13C NMR &75 MHz, CDCl3) d 21.8, 22.5, 27.6, 41.5, 43.9,
57.8, 62.9, 69.4, 71.7, 77.9, 78.2, 80.5, 109.0, 127.3, 128.1,
128.2, 128.4, 128.7, 136.9, 139.0, 156.9, 169.9, 170.6. MS
&FAB) m/z 525 &M1H). Anal. calcd for C28H32O8N2: C,
64.11; H, 6.15; N, 5.34. Found C, 64.12; H, 6.19; N, 5.34.
The epimer at C-4 of 38. Mp 185±1868C &as white tiny
4.1.23. Benzylurea 37. To a solution of the diacetate 36
&1.25 g, 2.04 mmol) in DMF &40 mL) were successively
added Na2CO3 &1.08 g, 10.2 mmol) and BnNH2 &0.29 mL,
2.65 mmol). The solution was vigorously stirred at 1408C
for 15 min. After cooling to rt, the mixture was diluted with
AcOEt, and the resulting solution was poured into an ice-
cold sat. NH4Cl solution. The mixture was extracted with
AcOEt &£3). The combined organic layer was washed with
water &£2) and brine &£1), dried over anhydrous Na2SO4,
and concentrated under reduced pressure. The crude product
28
needles from ether±hexane). [a]D 14.48 &c 0.69,
CHCl3). IR &KBr) nmax 3420, 3347, 2922, 1745, 1734,
1693, 1554, 1256, 1200, 1059 cm21. H NMR &400 MHz,
1
CDCl3) d 1.24 &1H, dd, J15.5, 11 Hz, Me±C±CHaxHeq),
1.58 &3H, s, CH3), 2.09 &3H, s, OAc), 2.53 &1H, ddd, J15.5,
8, 1 Hz, Me±C±CHaxHeq), 3.20&1H, dd, J11, 8 Hz,
±CH±), 3.32 &3H, s, OCH3), 4.30&1H, dd, J15, 6 Hz,