Md. S. Islam et al. / Tetrahedron 63 (2007) 1074–1079
1077
(
75 MHz in CDCl ): d¼19.6, 30.1, 38.6, 49.9, 69.3, 135.4,
3.2.4. 6,8-Dihydroxy-3-methyl-3,4,4a,5,6,7-hexahydro-
1H-isochromen-1-one (6D12)—one-pot reaction. 4-(Di-
methylamino)pyridine (35 mg, 5.6 mol %) was added to a
solution of hydroxyl aldehyde 9 (583 mg, 5.11 mmol) in
dry benzene (110 ml). After 8 min, a solution of diketene
(465 mg, 5.52 mmol) in benzene (90 ml) was added to the
3
152.2, 166.3, 193.5, 200.3. ESI-HRMS m/z calcd for
C H O Na [M+Na] 221.0784, found 221.0753.
+
1
0 14 4
3
.2.2. (3R,4aR)-6-Hydroxy-3,8-dimethyl-4,4a,5,6-tetra-
hydro-1H,3H-pyrano[3,4-c]pyran-1-one (11). To a stirring
solution of ester 10 (108 mg, 0.545 mmol) in dry
benzene (3 ml) was added K CO (2.6 mg, 3.5 mol %) and
ꢁ
reaction mixture through cannula over 15 min at 10 C and
it was stirred for further 30 min. Then K CO (75 mg,
2
3
2
3
1
2
8-crown-6 (23 mg, 16 mol %) at room temperature. After
.5 h, solvent was evaporated in vacuo and the residue was
11 mol %) and 18-crown-6 (414 mg, 30.7 mol %) were
added and stirring was continued for 2.5 h at room tempera-
ture. After completion of Michael addition, the mixture was
refluxed for 3 h to give aldol product. After cooling down to
room temperature, the reaction mixture was quenched with
chromatographed over silica gel. Elution with n-hexane/
ethyl acetate (7:3–1:1) afforded hemiacetal 11 (65 mg,
6
0%, b-OH/a-OH¼2.4:1) as a white solid.
H O (15 ml) and the organic layer was separated. The aque-
2
IR (CDCl solution): 3256 (br), 2983, 2935, 2862, 1674,
3
ous layer was extracted with dichloromethane (300 ml).
Both of the benzene part and the dichloromethane part
were washed with brine (10 ml) separately and the combined
brine part was re-extracted with dichloromethane (50 ml).
1
9
583, 1387, 1283, 1257, 1158, 1133, 1106, 1045, 999,
59, 943, 882, 837 cm . H NMR (300 MHz in CDCl )
ꢀ
1 1
3
for b-OH-isomer: d¼1.37 (3H, d, J¼6.3 Hz), 1.26–1.51
(
4
2H, m), 1.90–2.29 (2H, m), 2.36 (3H, s), 2.84 (1H, m),
.45 (1H, m), 5.59 (1H, br s). H NMR (300 MHz in
Combined organic layer was then dried over MgSO . After
4
1
filtration, the solvent was evaporated in vacuo and the
residue was chromatographed over silica gel. Elution with
n-hexane/ethyl acetate (1:1–4:5) afforded a mixture of 6
and 12 (715 mg, 71%, 6/12¼3.4:1) as a white solid, whose
spectral data were identical to those of the product obtained
by stepwise reactions.
CDCl ) for a-OH-isomer: d¼1.36 (3H, d, J¼6.3 Hz),
3
1
(
.26–1.51 (2H, m), 1.90–2.29 (2H, m), 2.35 (3H, s), 2.71
1H, m), 4.42 (1H, m), 5.36 (1H, m).
3
1
.2.3. 6,8-Dihydroxy-3-methyl-3,4,4a,5,6,7-hexahydro-
H-isochromen-1-one [12 and (D)-6-hydroxyramulosin
(
1
6)]—stepwise reaction. To a stirring solution of hemiacetal
1 (48 mg, 0.24 mmol) in dry benzene (3 ml) was added
K CO (1.2 mg, 3.5 mol %) and 18-crown-6 (10.2 mg,
3.2.5. 8-Hydroxy-3-methyl-3,4,4a,5-tetrahydro-1H-
isochromen-1-one (13). To a stirring solution of bicyclic
diol 6+12 (135 mg, 0.681 mmol) in chloroform (12 ml)
2
3
ꢁ
1
6 mol %). This mixture was then refluxed for 2 h and
was added Martin sulfurane (1 equiv) at 0 C. After 3 h,
cooled to room temperature. The solvent was evaporated
in vacuo and the residue was chromatographed over silica
gel. Elution with n-hexane/ethyl acetate (1:1) afforded a
mixture of 6 and 12 (45 mg, 94%, 6/12¼3.4:1) as a white
solid. Diastereomers were separated by preparative TLC
using diethyl ether as the developing solvent to afford 6
solvent was evaporated in vacuo and the residue was chro-
matographed over silica gel. Elution with n-hexane/ethyl
acetate (4:1) afforded 13 (91 mg, 74%) as a white solid.
ꢁ
26
Mp 83–84 C. [a]D +174 (c 0.40, CHCl ). IR (KBr):
3
n¼3435, 3000–2800, 1647, 1575, 1388, 1313, 1248, 1185,
ꢀ1
1
(
35 mg, 73%) and 12 (4.1 mg, 8.6%). Both of the isomers
were recrystallized from ethyl acetate/n-hexane to give
1146, 1092, 873, 799 cm
.
H NMR (300 MHz in
CDCl ): d¼1.41 (3H, d, J¼6.3 Hz), 1.51 (1H, m), 1.92–
3
colorless needles.
2.07 (2H, m), 2.34 (1H, dt, J¼17.1, 6.3 Hz), 2.87 (1H, m),
13
4
.39 (1H, m), 6.07 (1H, dd, J¼9.9, 3.3 Hz), 6.44 (1H, ddd,
ꢁ
24
D
(
+)-6-Hydroxyramulosin (6): mp 134–135 C. [a] +91
J¼9.9, 6.9, 2.1 Hz), 12.84 (1H, s). C NMR (75 MHz in
(
1
1
c 0.43, MeOH). IR (KBr): n¼3448, 3000–2840, 1639,
CDCl ): d¼21.3, 29.8, 30.5, 36.6, 74.7, 92.5, 124.5, 139.4,
3
599, 1444, 1401, 1352, 1289, 1257, 1233, 1166, 1145,
H NMR
168.0, 171.8. ESI-HRMS m/z calcd for C H O Na
1
0 12 3
ꢀ1
1
+
107, 1062, 1028, 944, 867, 830 cm
.
[M+Na] 203.0679, found 203.0699.
(
300 MHz in CDCl ): d¼1.25–1.46 (2H, m), 1.40 (3H, d,
3
J¼6.3 Hz), 1.66 (1H, d, J¼3.0 Hz), 1.92 (1H, m), 2.01
3.2.6. (3R,4aS)-(D)-Ramulosin (5). According to the method
of Pietrusiewicz, reduction of diene 13 (¼A) (45.5 mg,
0.253 mmol) afforded 5 (37.1 mg, 81%) as a white solid.
2
9
(
4
4
1H, m), 2.41 (1H, d, J¼19.5 Hz), 2.66 (1H, ddd, J¼19.5,
.5, 2.4 Hz), 2.92 (1H, br t, J¼11.1 Hz), 4.37 (1H, br s),
3
1
3
.52 (1H, m), 13.18 (1H, s). C NMR (75 MHz, CDCl ):
ꢁ
21
d¼21.7, 26.4, 35.7, 36.8, 37.5, 63.7, 76.8, 96.4, 171.4,
Mp 118–119 C. [a]D +19 (c 0.50, EtOH). IR (KBr):
n¼3422, 3000–2800, 1643, 1618, 1446, 1407, 1387, 1354,
1304, 1273, 1235, 1172, 1145, 1105, 1065, 1019, 957,
+
1
2
6
71.6. ESI-HRMS m/z calcd for C H O Na [M+Na]
10 14 4
21.0784, found 221.0812. Anal. Calcd for C H O : C,
1
0 14 4
ꢀ
1
1
0.59; H, 7.12. Found: C, 60.42; H, 6.87.
892, 831, 774 cm
.
H NMR (300 MHz in CDCl3):
d¼1.09–1.34 (2H, m), 1.38 (3H, d, J¼6.3 Hz), 1.62 (1H,
ꢁ
18
Compound 12: mp 127–128 C. [a]D +21 (c 0.07, MeOH).
IR (KBr): n¼3400 (br), 3000–2840, 1639, 1599, 1411,
m), 1.85–1.96 (3H, m), 2.38 (2H, m), 2.52 (1H, m), 4.46
(1H, m), 13.26 (1H, s). C NMR (75 MHz in CDCl3):
1
3
ꢀ
1
1
1
295, 1231, 1176, 1105, 1058, 870 cm
.
H NMR
d¼20.9, 21.7, 29.0, 29.5, 32.9, 37.4, 76.0, 96.8, 171.8,
+
(
300 MHz in CDCl ): d¼1.21–1.45 (2H, m), 1.39 (3H, d,
174.7. ESI-HRMS m/z calcd for C H O Na [M+Na]
10 14 3
3
J¼6.6 Hz), 1.67 (1H, d, J¼4.8 Hz), 1.97 (1H, m), 2.12
205.0835, found 205.0853.
(
1H, m), 2.35 (1H, ddd, J¼18.3, 9.9, 2.4 Hz), 2.60 (1H, br
t, J¼11.1 Hz), 2.80 (1H, dd, J¼18.3, 6.3 Hz), 4.04 (1H,
3.2.7. (R)-(L)-Mellein (1).
3.2.7.1. Aromatization by DDQ. To a stirring solution
of diene 13 (26.1 mg, 0.144 mmol) in dry benzene (2 ml)
m), 4.46 (1H, m), 13.14 (1H, s). ESI-HRMS m/z calcd for
C H O Na [M+Na] 221.0784, found 221.0744.
+
1
0 14 4