A. Imura et al. / Tetrahedron: Asymmetry 9 (1998) 2285–2291
2289
4
.1.3. 4-Butanoyloxy-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,10(4H)-
dione 5c
Yield 94.8%; mp 128–129°C; H-NMR (CDCl ) δ: 0.89–0.99 (m, 6H, CH CH and
1
3
3
2
CH CH CH CO), 1.63–1.73 (m, 2H, CH CH CH CO), 1.92–2.31 (m, 2H, CH CH ), 2.35–2.46
3
2
2
3
2
2
3
2
(
m, 4H, C –H and CH CH CH CO), 4.08–4.17 (m, 6H, C –H and OCH CH O), 5.26, 5.53 (ABq,
7 3 2 2 8 2 2
+
J=16.8 Hz, 2H, C –H), 6.09 (s, 1H, C –H); m/z 377 (M ).
1
5
4
.1.4. 4-Benzoyloxy-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,10(4H)-
dione 5d
Yield 89.6%; mp 179–180°C; H-NMR (CDCl ) δ: 1.03 (t, J=7.3 Hz, 3H, CH CH ), 2.08–2.29 (m,
1
3
3
2
2
H, CH CH ), 2.36 (t, J=6.9 Hz, 2H, C –H), 3.94–4.14 (m, 6H, C –H and OCH CH O), 5.32, 5.63
3 2 7 8 2 2
+
(ABq, J=17.2 Hz, 2H, C –H), 6.12 (s, 1H, C –H), 7.42–8.14 (m, 5H, Ar–H); m/z 411 (M ).
1
5
4.2. Enzymatic hydrolysis of 5a
The acetate 5a (35.0 g, 100 mmol) was suspended in ethyl acetate (180 ml) and 0.1 M phosphate
buffer pH 6.5 (720 ml). L-Cysteine hydrochloride (7.7 g) and papain (70 g) were added and the mixture
was stirred at 40°C for 40 h at pH 6.4–6.6 with an autotitrater and 10% aqueous sodium hydroxide. The
reaction mixture was filtered through Celite and extracted with dichloromethane (3×250 ml) to obtain
the mixture of 6 and 7a. The residue was chromatographed on silica. Elution with chloroform/acetone
(20/1) gave acetate 7a. After the fraction was evaporated in vacuo, the residue was dissolved in 50%
methanol, and potassium carbonate (18.0 g, 130 mmol) was added, and the mixture was left at room
temperature. The reaction mixture was evaporated by a half volume, and adjusted to pH 2 with 10%
hydrochloric acid, extracted with dichloromethane. The organic layer was evaporated in vacuo, and the
residue was crystallized from ethyl acetate to obtain colorless crystals of (S)-4-ethyl-6,6-(ethylenedioxy)-
7
,8-dihydro-1H-pyrano[3,4-f ]indolizine-3,10(4H)-dione 8 (13.5 g, 44.0%, >99% ee). Mp 169–170°C;
25
[
α]D +104.3 (c=0.55, CHCl ); H-NMR (CDCl ) δ: 0.98 (t, J=7.3 Hz, 3H, CH CH ), 1.62 (m, 2H,
3
3
3
2
CH CH ), 2.42 (t, J=6.9 Hz, 2H, C –H), 4.13 (m, 6H, C –H and OCH CH O), 5.16, 5.61 (ABq,
3
2
7
8
2
2
+
−1
J=16.4 Hz, 2H, C –H), 6.57 (s, 1H, C –H); m/z 307 (M ); IR (KBr) 3311, 1755, 1658 and 1590 cm ;
1
5
anal. calcd for C H NO : C, 58.63; H, 5.58; N, 4.56. Found: C, 58.61; H, 5.66; N, 4.55. Elution
15
17
6
with chloroform/acetone (10/1) gave an alcohol which was crystallized from ethyl acetate to afford
colorless crystals of (R)-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-1H-pyrano[3,4-f ]indolizine-3,10(4H)-
dione 6 (13.8 g, 45.0%, 98.2% ee). Mp 168–169°C; [α]D25 −103.1 (c=0.55, CHCl ). The H-NMR and
1
3
IR spectra of compound 6 obtained here were identical to those of 8. Anal. calcd for C H NO : C,
15
17
6
58.63; H, 5.58; N, 4.56. Found: C, 58.71; H, 5.69; N, 4.54.
4.3. 4-Chloro-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,10(4H)-dione 9
Pyridine (7.3 ml, 90.0 mmol) and thionylchloride (4.0 ml, 54.6 mmol) were added to the solution of 6
(12.0 g, 39.0 mmol) in dichloromethane (100 ml), and the mixture was refluxed for 7 h. After cooling,
the reaction mixture was dropped in 10% aqueous sodium hydrogen carbonate solution (300 ml). The
organic layer was washed with water, dried, and evaporated in vacuo. The residue was crystallized from 2-
1
propanol, yielding yellow crystals (10.9 g, 85.9%). Mp 125°C (dec.); H-NMR (CDCl ) δ: 0.95 (t, J=7.3
3
Hz, 3H, CH CH ), 2.08–2.31 (m, 4H, CH CH and C –H), 4.01–4.14 (m, 6H, C –H and OCH CH O),
.38, 5.44 (ABq, J=16.8 Hz, 2H, C –H), 6.44 (s, 1H, C –H); m/z 326 (M ); IR (KBr) 1751, 1666 and
3
2
3
2
7
8
2
2
+
5
1 5