(()-Isosteviol and (()-Beyer-15-ene-3â,19-diol
J . Org. Chem., Vol. 63, No. 22, 1998 7951
reaction was stirred for 8 h and quenched with water (2 mL),
followed by 15% aqueous NaOH (2 mL) and another portion
of water (6 mL). Filtration and further evaporation of the
solvent gave 3.15 g (98%) of 22: 1H NMR 5.73 (ddt, 1, J )
16.6, 10.0, 6.4), 5.38 (dt, 1, J ) 1.0, 6.8), 5.22 (br t, 1, J ) 6.7),
5.03 (br d, 1, J ) 16.6), 4.98 (br d, 1, J ) 10.0), 4.71 (br s, 1),
4.68 (br s, 1), 3.95 (br s, 2), 2.79 (br d, 2, J ) 6.4), 2.23-1.95
(m, 8), 1.71 (s, 3), 1.65 (s, 3), 1.46 (br s, 1, OH); 13C NMR 145.4,
136.4, 136.1, 134.6, 125.7, 125.5, 115.0, 109.8, 68.6, 37.8, 36.4,
34.8, 26.1, 25.9, 22.3, 13.5; IR (neat) 3323, 3076, 1648, 1637,
995, 911, 887. Anal. Calcd for C16H26O: C, 81.99; H, 11.18.
Found: C, 81.68; H, 10.62.
1.74 (m, 2), 1.62-1.05 (m, 11), 1.35 (s, 3), 1.26 (t, 3, J ) 7.1),
1.06 (s, 3), 1.04 (s, 3); 13C NMR 209.0, 173.7, 159.7, 101.4, 61.0,
58.5, 57.6, 57.0, 54.8, 43.9, 42.1, 41.2, 41.0, 40.6, 40.2, 37.7,
36.6, 23.7, 22.3, 21.1, 20.9, 13.9, 13.2; IR (neat) 1714, 1652.
Anal. Calcd for C23H34O3: C, 77.05; H, 9.56. Found: C, 76.66;
H, 9.22.
1
Data for the epimer of 2 at C4: H NMR 4.74 (br s, 1), 4.64
(br s, 1), 4.26-4.10 (m, 2), 2.80 (br d, 1, J ) 15.6), 2.57 (ddd,
1, J ) 16.8, 12.2, 7.0), 2.44 (ddd, 1, J ) 16.8, 6.4, 3.1), 2.30-
0.92 (m, 15), 1.34 (s, 3), 1.25 (t, 3, J ) 7.0), 1.07 (s, 3), 1.05 (s,
3); 13C NMR 211.0, 173.3, 159.6, 101.6, 61.2, 61.0, 57.1, 55.1,
51.5, 43.9, 42.2, 41.2 (2 C), 39.8, 37.7, 36.3, 34.5, 23.8, 22.6,
20.7, 17.0, 14.7, 14.1.
1-Br om o-2,10-dim eth yl-6-(2-pr open yl)-2E,6E,10-u n deca-
tr ien e (23). Et3N (0.92 mL, 6.6 mmol) was added dropwise
to a mixture of alcohol 22 (780 mg, 3.3 mmol) and MsCl (0.4
mL, 5.0 mmol) in 25 mL of THF at -45 °C. The reaction was
stirred for 1 h and then warmed to 0 °C at which time a
solution of LiBr (1.15 g, 13.2 mmol) in 5 mL of THF was added
via cannula. The resulting mixture was stirred for 2 h at 0
°C and then diluted with ice-cold water and extracted with
hexane. The combined organic extracts were washed with
saturated NaHCO3, water, and brine and dried (MgSO4). The
solvent was removed under reduced pressure giving 1.00 g of
crude product. Purification by flash chromatography on silica
gel (100:1 hexane/EtOAc followed by 50:1 hexane/EtOAc)
afforded 705 mg (72%) of pure bromide 23: 1H NMR 5.73 (ddt,
1, J ) 16.6, 10.0, 6.4), 5.57 (br t, 1, J ) 6.3), 5.21 (br t, 1, J )
6.8), 5.03 (br d, 1, J ) 16.6), 4.98 (br d, 1, J ) 10.0), 4.71 (br
s, 1), 4.68 (br s, 1), 3.96 (br s, 2), 2.78 (br d, 2, J ) 6.4), 2.21-
1.98 (m, 8), 1.74 (s, 3), 1.72 (s, 3); 13C NMR 145.5, 136.1, 136.0,
131.9, 131.1, 126.0, 115.1, 109.9, 41.7, 37.9, 36.0, 34.8, 26.8,
26.0, 22.4, 14.6; IR (neat) 3075, 1649, 1636, 993, 912, 888.
E t h yl 2,6,14-Tr im et h yl-3-oxo-10-(2-p r op en yl)-6E,10E,
14-pen tadecatr ien oate (1). Ethyl 2-methylacetoacetate (5.26
g, 36.5 mmol) was added dropwise to a solution of NaH (1.53
g, 38.3 mmol) and HMPA (3.81 mL, 21.9 mmol) in THF (240
mL) at 0 °C. The reaction was stirred for 1 h and then treated
with n-BuLi (15.3 mL, 38.3 mmol of 2.5 M in hexane). The
resulting mixture was stirred for 1 h, and a solution of bromide
23 (2.71 g, 9.1 mmol) in THF (10 mL) was transferred to the
reaction via cannula. The reaction mixture was stirred for 2
h, quenched with saturated NH4Cl solution, and extracted with
Et2O. The combined organic layers were washed with water
and brine, dried (MgSO4), and concentrated. Flash chroma-
tography of the residue on silica gel (50:1 hexane/EtOAc) gave
2.74 g (83%) of pure 1: 1H NMR 5.73 (ddt, 1, J ) 16.6, 10.0,
6.4), 5.20 (br t, 1, J ) 6.8), 5.11 (dt, 1, J ) 1.4, 6.8), 5.03 (br d,
1, J ) 16.6), 4.98 (br d, 1, J ) 10.0), 4.71 (br s, 1), 4.68 (br s,
1), 4.19 (q, 2, J ) 7.1), 3.52 (q, 1, J ) 7.1), 2.78 (br d, 2, J )
6.4), 2.67 (dt, 1, J ) 17.1, 7.8), 2.58 (dt, 1, J ) 17.1, 7.4), 2.25
(br t, 2, J ) 7.8), 2.20-1.98 (m, 8), 1.72 (s, 3), 1.59 (s, 3), 1.33
(d, 3, J ) 7.1), 1.27 (t, 3, J ) 7.1); 13C NMR 205.5, 170.5, 145.6,
136.6, 136.3, 133.3, 125.5, 125.0, 115.0, 109.9, 61.2, 52.9, 40.1,
37.9, 36.8, 34.9, 33.2, 26.6, 26.0, 22.4, 16.0, 14.1, 12.7; IR (neat)
3075, 1745, 1716, 1650, 1448, 910, 887.
Partial data for 32 were determined from the mixture: 1H
NMR 5.76 (d, 1, J ) 11.0), 5.66 (ddd, 1, J ) 11.0, 9.3, 9.3).
Data for 33: 1H NMR 6.42 (d, 1, J ) 11.0), 5.47 (ddd, 1, J
) 11.0, 8.8, 8.8), 5.24 (br t, 1, J ) 7.4), 4.71 (br s, 1), 4.67 (br
s, 1), 4.25-4.05 (m, 2), 2.95 (ddd, 1, J ) 14.5, 14.5, 6.4), 2.85-
0.85 (m, 13), 2.37 (ddd, 1, J ) 14.5, 4.7, 2.4), 1.71 (s, 3), 1.32
(s, 3), 1.25 (t, 3, J ) 7.1), 1.07 (s, 3).
Eth yl (4r,8â,13â)-3-Hyd r oxy-13-m eth yl-16-k a u r en -18-
oa te (34). Sodium borohydride (22.0 mg, 5.8 mmol) was added
to a solution of 2 (51.5 mg, 0.14 mmol) in EtOH (1 mL) at 0
°C, and the resulting mixture was stirred for 1 h. The reaction
was warmed to room temperature, quenched with 1 M HCl,
and extracted with CH2Cl2. The combined organic extracts
were washed with water and brine and dried (MgSO4).
Removal of the solvent afforded 50.5 mg (99%) of 34: mp 99.0-
99.5 °C; 1H NMR 4.71 (br s, 1), 4.61 (br s, 1), 4.21-4.05 (m, 2),
3.45 (d, 1, J ) 12.0, OH), 3.06 (ddd, 1, J ) 12.0, 12.0, 4.5),
2.75 (br d, 1, J ) 16.7), 2.09-0.93 (m, 16), 1.92 (br d, 1, J )
16.7), 1.40 (s, 3), 1.30 (t, 3, J ) 7.1), 1.03 (s, 3), 0.79 (s, 3); 13
C
NMR 178.0, 160.0, 101.2, 78.4, 60.2, 57.1, 56.8, 55.4, 48.9, 43.9,
42.1, 41.3, 41.0, 41.0, 38.7, 37.7, 28.1, 23.8, 23.8, 21.8, 20.8,
14.1, 13.4; IR (neat) 3537, 3068, 1699, 1653, 872. Anal. Calcd
for C23H36O3: C, 76.62; H, 10.07. Found: C, 76.43; H, 9.82.
Eth yl (4r,8â,13â)-3-Hyd r oxy-13-m eth yl-16-oxo-17-n or -
k a u r a n -18-oa te (35). OsO4 (25 µL, 1.9 × 10-6 mmol of 2.5%
solution in tert-butyl alcohol) was added to a mixture of 34
(50.3 mg, 0.14 mmol), NaHCO3 (163 mg, 1.94 mmol), and
NaIO4 (249 mg, 1.16 mmol) in tert-butyl alcohol (3.6 mL) and
water (0.72 mL) at room temperature. The reaction was
stirred for 4 h, and another portion of OsO4 (25 µL) was added.
The resulting mixture was stirred overnight and then quenched
with 10% Na2S2O4. After being stirred for 30 min, the mixture
was extracted with ether. The combined organic extracts were
washed with water and brine and dried (MgSO4). Evaporation
of the solvent afforded 47 mg (93%) of 35: 1H NMR 4.14 (q, 2,
J ) 7.1), 3.44 (d, 1, J ) 12.1, OH), 3.08 (ddd, 1, J ) 12.1, 12.1,
4.2), 2.60 (dd, 1, J ) 18.5, 3.8), 2.00 (dddd, 1, J ) 13.5, 12.1,
11.2, 3.4), 1.93-1.00 (m, 15), 1.81 (d, 1, J ) 18.5), 1.42 (s, 3),
1.28 (t, 3, J ) 7.1), 0.98 (s, 3), 0.74 (s, 3); 13C NMR 222.1, 177.7,
78.2, 60.4, 56.6, 54.6, 54.1, 48.9, 48.8, 48.3, 41.4, 39.3, 38.6,
37.7, 37.3, 28.0, 23.8, 21.7, 20.5, 19.8, 14.0, 13.6; IR (CCl4) 3546,
1740, 1704.
E t h yl (4r,8â,13â)-13-Met h yl-3-oxo-16-k a u r en -18-oa t e
(2). A solution of â-keto ester 1 (2.74 g, 7.6 mmol) in MeOH
(10 mL) was added to a degassed solution of Mn(OAc)3‚2H2O
(4.08 g, 15.2 mmol) and Cu(OAc)2 (1.38 g, 7.6 mmol) in MeOH
(160 mL), and the resulting mixture was stirred for 2.5 h at
room temperature. The reaction was diluted with water and
extracted with CH2Cl2. The combined organic layers were
washed with saturated NaHCO3 solution, water, and brine and
dried (MgSO4). Evaporation of the solvent afforded 2.59 g of
crude product. Flash chromatography on silica gel (impreg-
nated with 20% AgNO3) (24:1 hexane/EtOAc) gave 940 mg
(35%) of pure 2, followed 10 mg (0.4%) of the epimer of 2 at
C4, 50 mg of 80% pure 32 (1.5%), 64 mg (2%) of 33, 57 mg
(1%) of 50% pure 33, and 397 mg of unidentified products with
2-propenyl and 4-methyl-4-pentenyl side chains, and polymeric
material.
Eth yl (4r,8â,13â)-13-Meth yl-16-oxo-17-n or k a u r -3-en -18-
oa te (36). A mixture of 35 (18.4 mg, 0.051 mmol), PPh3 (53.3
mg, 0.2 mmol), and DEAD (32 µL, 0.2 mmol) in 1.0 mL of THF
was heated at reflux overnight. Evaporation of the solvent
and partial purification of the reaction mixture by flash
chromatography on silica gel (10:1 hexane/EtOAc) afforded
23.4 mg of 50% pure 36 that was carried on to the next step
without purification: 1H NMR 5.61 (br s, 2), 4.09 (q, 2, J )
7.1), 2.59 (dd, 1, J ) 18.7, 3.8), 2.04 (br d, 1, J ) 17.0), 1.97
(br d, 1, J ) 12.0), 1.81 (d, 1, J ) 18.7), 1.71-1.20 (m, 12),
1.30 (s, 3), 1.23 (t, 3, J ) 7.1), 0.99 (s, 3), 0.81 (s, 3).
Eth yl (4r,8â,13â)-13-Meth yl-16-oxo-17-n or k a u r a n -18-
oa t e (37). The 50% pure 36 (23.4 mg, approximately 0.03
mmol) and 5 mg of 5% Pd on carbon in EtOH (3 mL) was
stirred under 1 atm of H2 overnight. Filtration and removal
of the solvent gave 17.2 mg of crude 37. Flash chromatography
on silica gel (50:1 hexane/EtOAc) afforded 14 mg (79% for two
steps) of pure 37: 1H NMR 4.10 (q, 2, J ) 7.1), 2.64 (dd, 1, J
) 18.7, 3.7), 2.18 (br d, 1, J ) 13.5), 1.90 (dddd, 1, J ) 14.5,
3.8, 3.8, 3.8), 1.86-1.10 (m, 14), 1.80 (d, 1, J ) 18.7), 1.26 (t,
1
Data for 2: mp 87.0-88.0 °C; H NMR 4.73 (br s, 1), 4.63
(br s, 1), 4.23-4.04 (m, 2), 2.94 (ddd, 1, J ) 14.8, 14.8, 6.6),
2.81 (dd, 1, J ) 17.0, 2.4), 2.36 (ddd, 1, J ) 14.8, 4.8, 2.4),
2.05 (ddd, 1, J ) 13.2, 6.6, 2.4), 1.97 (dt, 1, J ) 17.0, 2.4), 1.90-