Synthesis and Absolute Configuration of Liverwort Diterpenes
purified by HPLC (Develosil 60-10, 20φ × 250 mm, hexane:
EtOAc ) 9:1, 9.0 mL/min) to yield 26 (65.8 mg, 21%), 27 (174
mg, 56%), and a mixture of other isomers (41.2 mg, 13%). 26:
oil; [R]19D -94.2 (c 1.2, CHCl3); FTIR 2230 cm-1; 1H NMR (600
MHz) δ 0.93 (3H, s), 1.39 (1H, qd, J ) 10.8, 1.2 Hz), 1.57-
1.73 (4H, m), 1.78 (3H, t, J ) 1.4 Hz), 1.85 (1H, br d, J ) 14.0
Hz), 2.04 (1H, dddd, J ) 13.7, 11.0, 8.2, 5.2 Hz), 2.10 (1H, dd,
J ) 14.0, 5.5 Hz), 2.11 (1H, m), 2.14 (1H, dtd, J ) 14.0, 10.2,
1.4 Hz), 3.04 (1H, td, J ) 9.9, 4.9 Hz), 5.41 (1H, ddt, J ) 8.9,
4.4, 1.4 Hz); 13C NMR (150 MHz) δ 17.7 (CH3), 23.8 (CH2), 26.6
(CH2), 27.0 (CH3), 32.3 (CH), 33.3 (CH2), 40.0 (CH2), 41.1 (CH2),
42.4 (C), 55.0 (CH), 122.1 (CH), 122.9 (C), 139.3 (C); MS (EI)
m/z 189 (M+), 174, 133, 121, 68 (base); HRMS (EI) found m/z
in THF at 0 °C, and the mixture was stirred overnight at room
temperature. Water was added, and the mixture was extracted
with ether. The organic layer was washed with brine, dried
(MgSO4), and evaporated to give a residue (29.4 mg), which
was used in the next step without purification. The residue
was dissolved in CH2Cl2 (5 mL), and was treated with PCC
(135.8 mg, 0.630 mmol) at room temperature for 24 h. After
filtration, the solvent was evaporated to give a residue (36.8
mg), which was purified by silica gel column chromatography
(elution with hexane-EtOAc gradient; 0-50%) to yield a
mixture of aldehydes 35 and 36 (14.4 mg, 63%): oil; FTIR 1670
cm-1; 1H NMR (300 MHz) δ 0.95 (t, J ) 9.9 Hz), 1.33 (s), 1.20-
1.74 (m), 2.11 (s), 1.88-2.19 (m), 2.32 (q, J ) 6.6 Hz), 2.46 (td,
J ) 10.8, 6.3 Hz), 2.62-2.81 (m), 3.58 (td, J ) 6.6, 6.3 Hz),
5.84 (d, J ) 8.1 Hz), 5.95 (dd, J ) 8.1, 0.9 Hz), 9.96 (d, J ) 8.1
Hz), 9.99 (d, J ) 8.1 Hz); 13C NMR (75 MHz) δ 14.6, 17.5, 23.1,
23.3, 26.8, 35.9, 39.9, 40.0, 41.1, 44.4, 53.1, 57.8, 60.0, 60.7,
127.8, 165.6, 189.8, 191.3; MS (EI) m/z 248 (M+), 230, 197, 159,
145, 119, 95 (base); HRMS (EI) found m/z 248.1799 (M+),
C16H24O2 requires 248.1776.
189.1525 (M+), C13H19N requires 189.1517. 27: [R]23 +66.2
D
(c 1.0, CHCl3); FTIR 2230 cm-1
;
1H NMR (400 MHz) δ 1.05
(3H, s), 1.55 (1H, ddd, J ) 13.2, 5.9, 3.7 Hz), 1.64 (3H, s), 1.67-
2.00 (6H, m), 2.00-2.23 (2H, m), 2.29 (1H, dd, J ) 15.8, 5.5
Hz), 2.57 (1H, d, J ) 15.8 Hz), 3.02 (1H, m), 5.26 (1H, br d, J
) 5.5 Hz); 13C NMR (100 MHz) δ 25.5 (CH3), 27.0 (CH2), 29.4
(CH2), 29.8 (CH3), 34.7 (CH2), 36.7 (CH), 37.0 (CH2), 41.6 (CH2),
45.9 (C), 51.1 (CH), 121.0 (CH), 121.4 (C), 136.7 (C); MS (EI)
m/z 189 (M+), 174, 133, 119, 81, 68 (base); HRMS (EI) found
m/z 189.1516 (M+), C13H19N requires 189.1517.
Meth yl 13(15)E,16E-3â,4â-Epoxy-19,20-din or sph en oloba-
13(15),16-d ien e-18-ca r boxyla te (37) a n d Meth yl 13(15)Z,-
16E-3â,4â-Ep oxy-19,20-d in or sp h en oloba -13(15),16-d ien e-
18-ca r boxyla te (38). To a solution of trimethyl phosphonoace-
tate (58.1 mg, 0.32 mmol) in THF (2 mL) was added a solution
of LHMDS (1 M, 0.24 mL, 0.24 mmol) in THF at room
temperature over 1.5 h. A solution of aldehydes 35 and 36 (14.4
mg, 0.058 mmol) in THF (3 mL) was added, and the mixture
was stirred for 3 h. Water was added at 0 °C, and the mixture
was extracted with ether. The organic layer was washed with
brine, dried (MgSO4), and evaporated to give a residue, which
was purified by silica gel column chromatography (elution with
hexane-EtOAc gradient; 0-30%) and HPLC (Nucleosil 50-5,
4.6φ × 250 mm, hexane:EtOAc ) 3:1, 1.0 mL/min) to yield
(1S,7R,8S)-8-Acet yl-1,4-d im et h ylb icyclo[5.3.0]d ec-3-
en e (30). A solution of 26 (46.6 mg, 0.25 mmol) in ether (1.2
mL) was treated with MeLi (1.14 M, 1.1 mL, 1.3 mmol) in ether
at 0 °C and stirred overnight at room temperature. Water was
added, and the mixture was extracted with ether. The organic
layer was washed with brine, dried (MgSO4), and evaporated
to give a residue (39.7 mg). The residue was dissolved in MeOH
(4 mL), and K2CO3 (266 mg, 1.9 mmol) was added. The mixture
was heated at 45 °C for 24 h. Water was added, and the solvent
was evaporated. The residue was extracted with ether and the
organic layer was washed with brine, dried (MgSO4), and
evaporated to give ketone 30 (37.3 mg), which was used in
esters 37 and 38 (3.9 mg, 22%): oil; FTIR 1720, 1630 cm-1
;
the next step without purification: oil; [R]19 +35.5 (c 0.7,
D
1H NMR (300 MHz, C6D6) δ 0.50 (s), 0.59 (s), 0.68 (s), 0.88-
1.48 (m), 1.22 (s), 1.36 (d, J ) 1.2 Hz), 1.48-1.71 (m), 1.85 (td,
J ) 13.8, 6.3 Hz), 2.01-2.20 (m), 2.53-2.65 (m), 3.04 (td, J )
10.8, 6.3 Hz), 3.49 (s), 3.54 (s), 5.85 (d, J ) 12.3 Hz), 5.92 (d,
J ) 12.3 Hz), 6.03 (d, J ) 15.0 Hz), 6.04 (d, J ) 15.3 Hz), 7.90
(dd, J ) 15.3, 11.7 Hz), 8.02 (dd, J ) 15.0, 11.7 Hz); 13C NMR
(75 MHz, C6D6) δ 13.6, 17.8, 17.9, 20.0, 23.8, 24.0, 26.5, 26.8,
36.9, 37.0, 40.5, 40.7, 42.0, 42.1, 44.6, 44.7, 44.9, 51.5, 53.9,
58.2, 58.6, 59.7, 60.7, 119.9, 120.3, 125.1, 126.8, 140.6, 141.7,
151.3, 151.5, 168.1, 168.2; MS (EI) m/z 304 (M+), 286, 178, 145,
125, 93 (base); HRMS (EI) found m/z 304.2050 (M+), C19H28O3
requires 304.2039.
CHCl3); FTIR 1710 cm-1; H NMR (300 MHz) δ 0.74 (3H, s),
1
1.10-1.27 (1H, m), 1.43 (1H, q, J ) 3.0 Hz), 1.47 (1H, dd, J )
8.7, 5.7 Hz), 1.41-1.51 (1H, m), 1.57-1.71 (2H, m), 1.74 (3H,
s), 1.78 (1H, td, J ) 11.1, 3.0 Hz), 1.89-2.15 (4H, m), 2.15
(3H, s), 2.67 (1H, td, J ) 11.1, 6.3 Hz), 5.38 (1H, m); 13C NMR
(75 MHz) δ 18.1 (CH3), 24.7 (CH2), 25.2 (CH2), 27.1 (CH3), 29.7
(CH3), 33.8 (CH2), 40.2 (CH2), 40.5 (CH2), 42.2 (C), 56.3 (CH),
56.7 (CH), 122.3 (CH), 139.4 (C), 212.2 (C); MS (EI) m/z 206
(M+), 188, 163, 121, 107, 95 (base); HRMS (EI) found m/z
206.1684 (M+), C14H22O requires 206.1670.
(1S,3R,4S,7R,8S)-8-Acetyl-3,4-epoxy-1,4-dim eth ylbicyclo-
[5.3.0]d eca n e (28). A solution of ketone 30 (37.3 mg, 0.18
mmol) in CH2Cl2 (4 mL) was treated with mCPBA (70%, 78.9
mg, 0.32 mmol) at 0 °C for 1.5 h. Na2S2O3 (2 M) solution was
added, and the mixture was extracted with ether. The organic
layer was washed with 2 M Na2S2O3 solution and brine, dried
(MgSO4), and evaporated to give a residue, which was purified
by silica gel column chromatography (elution with hexane-
EtOAc gradient; 0-50%) to yield epoxide 28 (20.5 mg, 51%):
oil; [R]19D +37.2 (c 1.0, CHCl3); FTIR 1710 cm-1; 1H NMR (600
MHz) δ 0.92 (3H, s), 1.29 (1H, dq, J ) 13.2, 1.1 Hz), 1.31 (1H,
dd, J ) 11.3, 6.9 Hz), 1.33 (3H, s), 1.43 (1H, d, J ) 13.7 Hz),
1.47 (1H, dd, J ) 8.8, 5.5 Hz), 1.53 (1H, ddq, J ) 14.1, 6.6, 1.4
Hz), 1.60-1.66 (2H, m), 1.68 (1H, td, J ) 11.3, 2.7 Hz), 2.00-
2.08 (2H, m), 2.14 (3H, s), 2.28 (1H, q, J ) 6.9 Hz), 2.69 (1H,
td, J ) 11.3, 6.9 Hz), 2.74 (1H, t, J ) 7.2 Hz); 13C NMR (150
MHz) δ 17.4 (CH3), 23.3 (CH3), 23.7 (CH2), 25.3 (CH2), 29.6
(CH3), 35.8 (CH2), 39.5 (CH2), 40.6 (CH2), 44.3 (C), 55.5 (CH),
56.4 (CH), 60.0 (C), 60.7 (CH), 211.4 (C); MS (EI) m/z 222 (M+),
207, 179, 161, 137, 121, 107, 93 (base); HRMS (EI) found m/z
222.1606 (M+), C14H22O2 requires 222.1620.
(-)-13(15)E,16E-3â,4â-E p oxy-18-h yd r oxysp h en olob a -
13(15),16-d ien e (4) a n d (-)-13(15)Z,16E-3â,4â-Ep oxy-18-
h yd r oxysp h en oloba -13(15),16-d ien e (5). A solution of the
mixture of esters 37 and 38 (3.9 mg, 0.013 mmol) in ether (1.5
mL) was treated with MeLi (1.14 M, 0.045 mL, 0.051 mmol)
in ether at 0 °C for 3 h. Water was added, and the mixture
was extracted with ether. The organic layer was washed with
brine, dried (MgSO4), and evaporated to give a residue, which
was purified by HPLC (Nucleosil 50-5, 7.5φ × 250 mm, hexane:
EtOAc ) 75:15, 1.0 mL/min) to yield 4 (2.1 mg, 54%) and 5
(1.2 mg, 31%). 4: oil; [R]22 -37.4 (c 0.66, CHCl3); FTIR 3430
D
cm-1 1H NMR (400 MHz) δ 0.92 (3H, s), 1.32 (3H, s), 1.35
;
(6H, s), 1.68 (3H, d, J ) 1.1 Hz), 1.76-1.89 (1H, m), 2.03 (1H,
dd, J ) 13.5, 6.6 Hz), 2.25-2.37 (2H, m), 2.76 (1H, t, J ) 7.3
Hz), 5.73 (1H, d, J ) 15.4 Hz), 5.81 (1H, d, J ) 10.6 Hz), 6.44
(1H, dd, J ) 15.4, 10.6 Hz); 13C NMR (75 MHz) δ 13.0 (CH3),
17.5 (CH3), 23.2 (CH2), 23.4 (CH3), 26.2 (CH2), 29.9 (CH3), 29.9
(CH3), 36.1 (CH2), 39.9 (CH2), 41.3 (CH2), 44.0 (CH2), 52.7 (C),
57.5 (CH), 60.2 (C), 61.1 (C), 71.0 (C), 122.9 (CH), 125.2 (C),
139.2 (CH), 140.3 (C); MS (EI) m/z 304 (M+), 286, 268, 197,
159, 119, 107 (base); HRMS (EI) found m/z 304.2404 (M+),
C20H32O2 requires 304.2402. 5: oil; [R]23D -42.0 (c 0.84, CHCl3);
1H NMR (400 MHz) δ 0.97 (3H, s), 1.33 (3H, s), 1.34 (6H, s),
1.56 (3H, s), 1.76-1.89 (1H, m), 2.03 (1H, dd, J ) 13.2, 5.8
Hz), 2.30 (1H, dd, 13.6, 7.0 Hz), 2.77 (1H, t, J ) 7.0 Hz), 2.99
13(15)E-3â,4â-Ep oxy-17,18,19,20-tetr a n or sp h en olob-13-
(15)-en -16-a l (35) a n d 13(15)Z-3â,4â-Ep oxy-17,18,19,20-
tetr a n or sp h en olob-13(15)-en -16-a l (36). A solution of ep-
oxide 28 (20.5 mg, 0.092 mmol) in THF (1 mL) was treated
with vinylmagnesium bromide (0.95 M, 0.6 mL, 0.57 mmol)
J . Org. Chem, Vol. 67, No. 17, 2002 6039