Journal of Natural Products
Article
mmol) were stirred overnight at rt. By dilution with 2 mL of THF a
0.25 M solution of Zn(BH4)2 was obtained.
acetone/dry ice cooling bath was removed, and the mixture was stirred
until it reached rt. After 30 min at rt the mixture was diluted with 5 mL
of H2O and extracted with 4 × 5 mL of Et2O. The combined organic
layers were dried over MgSO4 and filtered. Solvents were removed
under reduced pressure at 30 °C, and then crude dia-19 (23 mg) was
first filtered via column chromatography (PE/EtOAc, 95/5); the
slightly impure isomer dia-19 was obtained (1.7 mg, 4.0 μmoL) after
preparative HPLC as a colorless oil: Rf (80/20 PE/EtOAc) 0.33; Rf
(90/10 PE/EtOAc) 0.09; 1H NMR (CDCl3, 600 MHz) δ 0.07 [3H, s,
Si(CH3)], 0.09 [3H, s, Si(CH3)], 0.68 (1H, mc, H-9a), 0.82−0.87 (1H,
ii. Preparation of Title Compound 4. In a separate flask compound
dia-18 (9.7 mg, 30 μmol, 1.00 equiv) was dissolved in 1 mL of THF
and cooled to 0 °C. After the addition of 0.82 mL of a preformed 0.25
M Zn(BH4)2 solution (0.21 mmol, 8.00 equiv) the ice bath was
removed and the mixture was stirred for 1 h at rt. After addition of
saturated aqueous NH4Cl the layers were separated and the aqueous
layer was extracted four times with EtOAc. The combined organic
layers were washed with a saturated solution of NaCl. The organic
layer was dried over MgSO4, and the solvent was removed under
reduced pressure. Product 4 (6.6 mg, 18 μmol, 60%) was isolated by
column chromatography on silica (20/80 pentane/Et2O) as slight
traces of a white solid: Rf (EtOAc) 0.35; [α]2D0 −20.8 (c 0.66; CHCl3);
FT-IR νmax 3444, 3008, 2927, 2858, 1737, 1724, 1456, 1366, 1353,
3
m, H-9b), 0.89 (3H, t, J22,21 = 7.22 Hz, H-22), 0.90 [9H, s,
SiC(CH3)3], 1.12 (1H, mc, H-8), 1.24−1.27 (4H, m, H-20, H-21),
1.28−1.40 (3H, m, H-19, H-10), 1.53−1.55 (3H, m, H-4a, H-5),
1.67−1.74 (1H, m, H-4b), 1.81−1.84 (2H, m, H-6), 1.85−1.87 (2H,
m, H-3), 2.02 (2H, mc, H-18), 2.17−2.22 (2H, m, H-15), 2.41−2.46
(2H, m, H-2), 3.55 (1H, mc, H-14), 3.91 (1H, mc, H-13), 4.07 (1H,
1
1231, 1218, 1052 cm−1; H NMR (CDCl3, 600 MHz) δ 0.71 (1H,
ddd, 3J9a,10 = 8.5 Hz, 3J9a,8 = 5.1 Hz, 2J9a,9b = 5.1 Hz, H-9a), 0.88 (3H, t,
3J22,21 = 6.9 Hz, H-22), 0.89 (1H, m, H-9b, overlapped), 1.14 (1H, mc,
H-8), 122−1.38 (6H, m, H-19, H-20, H-21), 1.43 (1H, mc, H-10),
1.49−1.59 (3H, m, H-5, H-4a), 1.70 (1H, mc, H-4b), 1,83 (2H, mc, H-
6), 1.85 (2H, mc, H-3), 2.00−2.06 (2H, m, H-18), 2.14−2.22 (1H, m,
H-15a), 2.23−2.31 (1H, m, H-15b), 2.40−2.47 (2H, m, H-2), 3.67
(1H, mc, H-14), 4.08 (1H, mc, H-13), 4.13 (1H, mc, H-7), 5.34 (1H,
3
3
mc, H-7), 5.30 (1H, dd, J11,10 = 8.52 Hz, J11,12 = 14.78 Hz, H-11),
5.36−5.40 (1H, m, H-16), 5.45−5.48 (1H, m, H-17), 5.49 (1H, dd,
3
3J12,13 = 6.14 Hz, J12,11 = 15.21 Hz, H-12); 13C NMR (CDCl3, 151
MHz) δ −4.4 [Si(CH3)], −4.0 [Si(CH3)], 12.3 (C-9), 14.2 (C-22),
18.3 [SiC(CH3)3], 19.5 (C-10), 22.7 (C-21), 24.4 (C-5), 24.8 (C-8),
26.0 [SiC(CH3)3], 26.7 (C-4), 27.6 (C-18), 29.3 (C-19), 29.4 (C-3),
31.8 (C-15), 31.9 (C-20), 32.9 (C-2), 37.4 (C-6), 73.3 (C-13), 75.5
(C-14), 81.8 (C-7), 124.6 (C-16), 129.2 (C-12), 132.7 (C-17), 133.9
(C-11), 176.8 (C-1); HPLC [Chiralpak IC, 250 × 10 mm, Fa. Daicel;
heptane/2-propanol 90/10; 2.5 mL/min; 25 bar (const.), 205 nm], tR
= 18.01 min.
3
3
4
ddd, J11,12 = 15.5 Hz, J11,10 = 8.8 Hz, J11,13 = 0.9 Hz, H-11), 5.39
(1H, dt, 3J16,17 = 10.7 Hz, 3J16,15 = 7.6 Hz, H-16), 5.56 (1H, dt, 3J17,16
10.7 Hz, 3J17,18 7.3 Hz, H-17), 5.62 (1H, dd, 3J12,11 = 15.4 Hz, 3J12,13
=
=
7.3 Hz, H-12); 13C NMR (CDCl3, 151 MHz) δ 12.3 (C-9), 14.2 (C-
22), 19.5 (C-10), 22.7 (C-20 or C-21), 24.3 (C-5), 25.1 (C-8), 26.7
(C-4), 27.6 (C-18), 29.3 (C-3), 29.4 (C-19), 30.2 (C-15), 31.7 (C-20
or C-21), 32.9 (C-2), 37.3 (C-6), 74.0 (C-14), 75.2 (C-13), 81.4 (C-
7), 124.8 (C-16), 126.3 (C-12), 133.9 (C-17), 136.5 (C-11), 176.7 (C-
1); HRMS m/z 387.2506 [M + Na]+ (calcd for C22H36O4Na,
387.2506)].
(13R)-Alcohol 19. Compound 19 (11 mg, 23 μmol, 38%) was
prepared in analogy with preparation of diastereomeric compound dia-
19 using 60 μmol (30 mg, 1.0 equiv) of the HWE compound 10 and
90 μmol (23 mg, 1.5 equiv) of CeCl3 diluted in 0.3 mL of THF. For
the reduction, 3.7 mg of NaBH4 (98 μmol, 1.6 equiv) was used: Rf
(80/20 PE/EtOAc) 0.36; 1H NMR (600 MHz, CDCl3) δ 0.07 [3H, s,
Si(CH3)], 0.09 [3H, s, Si(CH3)], 0.68 (1H, mc, H-9a), 0.83−0.86 (1H,
m, overlapped, H-9b), 0.88 (3H, t, 3J22,21 = 7.16 Hz, H-22), 0.90 [9H,
s, SiC(CH3)3], 1.11 (1H, mc, H-8), 1.24−1.27 (4H, m, overlapped, H-
20, H-21), 1.28−1.40 (3H, m, H-19, H-10), 1.51−1.56 (3H, m, H-4a,
H-5), 1.68−1.72 (1H, m, H-4b), 1.81−1.84 (2H, m, H-6), 1.85−1.87
(2H, m, H-3), 2.01 (2H, mc, H-18), 2.17−2.21 (2H, m, H-15), 2.41−
2.46 (2H, m, H-2), 3.55 (1H, mc, H-14), 3.89 (1H, mc, H-13), 4.07
(13S,14R)-Diastereomer 2. Compound 18 (10 mg, 30 μmol, 1.0
equiv) was dissolved in 1 mL of THF and cooled to 0 °C. After the
addition of 0.82 mL of a 0.25 M Zn(BH4)2 solution (0.21 mmol, 8.00
equiv) the ice bath was removed. The mixture was stirred for 1 h at rt;
then saturated aqueous NH4Cl was added. The aqueous layer was
extracted four times with EtOAc, and the combined organic layers
were washed with brine. The organic layer was dried over MgSO4, and
the solvent was removed under reduced pressure. Product 2 (5.2 mg,
14 μmol, 52%) was isolated after chromatography on silica (20/80
pentane/Et2O) as slight traces of a white solid: Rf (EtOAc) 0.35, Rf
(Et2O) 0.20, Rf (50/50 PE/EtOAc) 0.25; [α]2D0 −12.2 (c 0.18;
CHCl3); FT-IR νmax 3433, 3003, 2963, 2927, 2860, 1717, 1464, 1449,
1350, 1328, 1237, 1135, 1052, 1044, 1001, 969 cm−1; 1H NMR
3
3
(1H, mc, H-7), 5.27 (1H, dd, J11,10 = 8.40 Hz, J11,12 = 15.33 Hz, H-
11), 5.37 (1H, dtt, 3J16,17 = 10.7 Hz, 3J16,15 = 7.4 Hz, 4J16,14 = 1.6 Hz, H-
16), 5.45−5.49 (1H, m, H-17), 5.48 (1H, dd, 3J12,13 = 6.41 Hz, 3J12,11
=
15.59 Hz, H-12); 13C NMR (CDCl3, 151 MHz) δ −4.4 [Si(CH3)],
−4.0 [Si(CH3)], 12.1 (C-9), 14.2 (C-22), 18.3 [SiC(CH3)3], 19.6 (C-
10), 22.7 (C-21), 24.4 (C-5), 24.9 (C-8), 26.0 [SiC(CH3)3], 26.7 (C-
4), 27.6 (C-18), 29.3 (C-19), 29.4 (C-3), 31.7 (C-15), 31.9 (C-20),
32.9 (C-2), 37.4 (C-6), 73.4 (C-14), 75.5 (C-13), 81.8 (C-7), 124.6
(C-16), 129.2 (C-12), 132.8 (C-17), 134.3 (C-11), 176.7 (C-1).
(13S,14S)-Diastereomer 3 (Solandelactone I). Crude com-
pound dia-19 (39 mg, 80 μmol, 1.0 equiv) was dissolved in 1.0 mL of
THF and cooled to 0 °C. After the addition of TBAF (26 mg, 80
μmol, 1.0 equiv) the reaction was stirred for 4.5 h at rt; then 10 mL of
H2O was added. The aqueous layer was extracted with 5 × 10 mL of
Et2O, and the combined organic layers were dried over MgSO4 and
filtered. The solvent was evaporated at 30 °C using a rotary
evaporator; then crude 3 (22 mg, 78%) was purified by preparative
HPLC. Solandelactone I (3) (11 mg, 30 μmol, 38%) was obtained as a
colorless oil: Rf (Et2O) 0.46; Rf (PE/EtOAc 80/20) 0.03; Rf (EtOAc)
0.68; [α]2D5 −30.6 (c 1.00; CHCl3), [α]2D5 −48.6 (c 1.00; MeOH); FT-
IR νmax 3405, 3007, 2925, 2857, 1717, 1453, 1350, 1328, 1235, 1184,
3
3
(CDCl3, 600 MHz) δ 0.71 (1H, ddd, J9a,10 = 8.5 Hz, J9a,8 = 5.1 Hz,
2J9a,9b = 5.1 Hz, H-9a), 0.89 (3H, t, J22,21 = 7.1 Hz, H-22), 0.90 (1H,
3
m, H-9b, overlapped), 1.14 (1H, mc, H-8), 1.21−1.40 (6H, m, H-19,
H-20, H-21), 1.43 (1H, mc, H-10), 1.50−1.56 (3H, m, H-5, H-4a),
1.70 (1H, mc, H-4b), 1.83 (2H, mc, H-6), 1.87 (2H, mc, H-3), 2.00−
2.07 (2H, m, H-18), 2.17−2.21 (1H, m, H-15a), 2.23−2.31 (1H, m,
H-15b), 2.41−2.47 (2H, m, H-2), 3.67 (1H, mc, H-14), 4.08 (1H, mc,
3
3
H-13), 4.13 (1H, mc, H-7), 5.34 (1H, ddd, J11,12 = 15.5 Hz, J11,10
=
4
3
8.7 Hz, J11,13 = 1.0 Hz, H-11), 5.39 (1H, d, J16,17 = 10.8 Hz, H-16),
3
3
5.57 (1H, dt, J17,16 = 10.8 Hz, J174,18 7.3 Hz, H-17), 5.62 (1H, ddd,
3J12,11 = 15.5 Hz, J12,13 = 7.3 Hz, J12,10 = 0.6 Hz, H-12); 13C NMR
3
(CDCl3, 151 MHz) δ 12.4 (C-9), 14.2 (C-22), 19.5 (C-10), 22.7 (C-
20 or C-21), 24.4 (C-5), 25.1 (C-8), 26.7 (C-4), 27.6 (C-18), 29.3 (C-
3), 29.4 (C-19), 30.2 (C-15), 31.7 (C-20 or C-21), 32.9 (C-2), 37.4
(C-6), 74.0 (C-14), 75.1 (C-13), 81.4 (C-7), 124.8 (C-16), 126.2 (C-
12), 133.8 (C-17), 136.4 (C-11), 176.7 (C-1); HRMS m/z 387.2507
[M + Na]+ (calcd for C22H36O4Na, 387.2506).
1
1162, 1138, 1050, 1003, 985, 964, 869, 755, 665 cm−1; H NMR
3
(CDCl3, 600 MHz) δ 0.71 (1H, mc, H-9a), 0.89 (3H, t, J22,21 = 6.6
Hz, H-22), 0.87−0.90 (1H, m, H-9b), 1.14 (1H, mc, H-8), 1.25−1.31
(4H, m, H-21, H-20), 1.32−1.37 (2H, m, H-19), 1.38−1.44 (1H, m,
H-10), 1.51−1.54 (2H, m, H-5), 1.56 (1H, m, H-4a), 1.68−1.72 (1H,
m, H-4b), 1.80−1.84 (2H, m, H-6), 1.85−1.88 (2H, m, H-3), 2.04
(2H, mc, 18-H), 2.21−2.30 (2H, m, 15-H), 2.40−2.47 (2H, m, 2-H),
3.48 (1H, mc, H-14), 3.91 (1H, mc, H-13), 4.12 (1H, mc, H-7), 5.38
(1H, dd, 3J11,10 = 8.80 Hz, 3J11,12 = 15.63 Hz, H-11), 5.42 (1H, mc, H-
(13S)-Alcohol dia-19. Under inert conditions, CeCl3 (80 μmoL,
19 mg, 1.4 equiv) was added to a solution of HWE reaction product
dia-10 (50 μmoL, 26 mg, 1.0 equiv) in 0.26 mL of THF. The
suspension was stirred for 1 h at rt. Afterward the suspension was
cooled to −78 °C and 80 μmoL of NaBH4 (3.0 mg, 1.4 equiv) and a
further 0.1 mL of THF were added. After further stirring of the
reaction mixture for 3 h at −78 °C 0.2 mL of H2O was added, the
H
J. Nat. Prod. XXXX, XXX, XXX−XXX