Synthesis of (()-Allocyathin B
2
and (+)-Erinacine A
J . Org. Chem., Vol. 63, No. 14, 1998 4739
for an additional 10 min, and 357 mg (1.0 mmol) of PhNTf
2
in
mL of CH
2
Cl
2
was stirred under N
2
at room temperature for
), and concen-
2
0 mL of THF was added rapidly. The solution was warmed
12 h. The solution was filtered, dried (MgSO
4
to room temperature, diluted with Et
2
O, washed with satu-
). Re-
trated under reduced pressure to give 18 mg of crude 2. Flash
rated NaHCO
3
solution and brine, and dried (MgSO
4
chromatography of the residue on silica gel (10:1 hexane/
1
moval of the solvent under reduced pressure followed by flash
chromatography on silica gel (hexane followed by 100:1 hexane/
EtOAc) gave 14 mg (94%) of pure allocyathin B
2
:
H NMR
9.45 (s, 1), 6.82 (dd, 1, J ) 2.5, 8.3), 5.9 (d, 1, J ) 8.3), 3.72
(m, 1), 3.16 (dd, 1, J ) 5.8, 18.2), 2.83 (h, 1, J ) 6.8), 2.55 (br
d, 1, J ) 18.2), 2.53 (m, 1), 2.41 (m, 2), 1.76-1.63 (m, 4), 1.34
(ddd, 1, J ) 3.5, 3.7, 13.7), 1.05 (d, 3, J ) 6.8), 1.00 (s, 3), 0.97
(d, 3, J ) 6.8), 0.96 (s, 3); 13C NMR 194.1, 155.1, 146.4, 144.3,
141.8, 137.7, 119.3, 74.0, 49.1, 48.2, 38.3, 36.5, 33.7, 29.2, 29.0,
1
EtOAc) gave 76 mg (75%) of pure 39: H NMR 6.32 (d, 1, J )
2
3
1
1
1
.6), 6.11 (dd, 1, J ) 4.6, 11.7), 5.90 (ddd, 1, J ) 2.6, 2.6, 11.7),
.52 (m, 1), 2.56 (h, 1, J ) 6.8), 2.35 (ddd, 1, J ) 7.0, 10.4,
5.9), 2.24 (ddd, 1, J ) 1.4, 9.3, 15.9), 1.93 (ddd, 1, J ) 4.2,
3.9, 13.9), 1.79 (ddd, 1, J ) 1.4, 7.0, 12.2), 1.69-1.45 (m, 4),
.10 (s, 3), 1.07 (s, 3), 0.99 (d, 3, J ) 6.8), 0.95 (d, 3, J ) 6.8);
C NMR 203.0, 151.8, 144.7, 135.1, 122.3, 121.4, 56.7, 46.3,
2.7, 41.5, 34.9, 28.1, 26.4, 25.9, 25.1, 22.2, 21.3, 21.2 (2 carbons
4
27.0, 26.5, 23.9, 21.5, 21.5; IR (CCl ) 3588, 1683, 1570; UV
1
3
1
13
(EtOH) λmax (ꢀ) 338 (17 000), 201 (7700). The H and C NMR
spectral data are identical to those provided by Professor
Kawagishi.
4
not observed); IR (neat) 1686, 1639; UV (EtOH) λmax (ꢀ) 274
nm (3600).
Er in a cin e A Tr ia ceta te (42). To a solution containing 8
Met h yl (3a r,5a â,10a â)-2,3,3a ,4,5,5a ,6,10a -Oct a h yd r o-
a,5a-dim eth yl-1-(1-m eth yleth yl)-6-oxocycloh ept[e]in den e-
-ca r boxyla te (40). CO gas was bubbled through a stirred
2 3
mg (0.027 mmol) of racemic allocyathin B (2) in 2 mL of CH -
CN was added 92 mg (0.27 mmol) of 2,3,4-tri-O-acetyl-R-D-
xylopyranosyl bromide followed by 8 mg (0.032 mmol) of
3
8
solution containing 72 mg (0.17 mmol) of triflate 39, 0.1 mL
0.76 mmol) of diisopropylethylamine, 3 mg (0.013 mmol) of
Pd(OAc) , and 7 mg (0.027 mmol) of Ph P in 15 mL of MeOH
at room temperature for 2.5 h. The solution was diluted with
Et O, washed with 1 N HCl and brine, and dried (MgSO ).
2 2
Hg(CN) and 8 mg (0.030 mmol) of HgCl at room temperature.
The solution was stirred at room temperature for 3.5 min and
diluted immediately with 40 mL of benzene. The solution was
(
2
3
washed three times with H
2
O and once with brine, dried
2
4
(MgSO ), and concentrated under reduced pressure to give 68
4
Removal of the solvent under reduced pressure followed by
mg of a crude yellow oil. Flash chromatography of the residue
on silica gel (5:1 hexane/EtOAc) gave 4 mg (50%) of recovered
flash chromatography on silica gel (25:1 hexane/EtOAc) gave
1
4
(
2 mg (75%) of pure 40: H NMR 7.22 (d, 1, J ) 1.6), 6.31
allocyathin B followed by 5 mg (34%, 68% from recovered
2
allocyathin B ) of a 1:1 mixture of 42 and 43. The diastere-
2
ddd, 1, J ) 1.6, 2.6, 11.3), 5.99 (dd, 1, J ) 5.0, 11.3), 3.83 (s,
3
1
1
1
), 3.43 (m, 1), 2.56 (h, 1, J ) 6.9), 2.34 (ddd, 1, J ) 7.1, 10.3,
5.6), 2.22 (ddd, 1, J ) 1.2, 9.2, 15.6), 1.89 (ddd, 1, J ) 1.2,
3.8, 13.8), 1.77 (ddd, 1, J ) 1.2, 7.1, 12.1), 1.73-1.43 (m, 4),
.12 (s, 3), 1.05 (s, 3), 0.96 (d, 3, J ) 6.9), 0.93 (d, 3, J ) 6.9);
C NMR 207.4, 166.1, 144.3, 140.8, 137.3, 135.6, 134.0, 123.3,
9.4, 52.5, 46.4, 42.3, 41.6, 34.8, 28.0, 26.2, 25.1, 24.9, 21.8,
1.4, 21.1; IR (neat) 1727, 1682; UV (EtOH) λmax (ꢀ) 286 nm
omeric glycosides were efficiently separated by further chro-
matography on silica gel (5:1 hexane/EtOAc).
Data for erinacine A triacetate diastereomer 43: 1H NMR
9.39 (s, 1), 6.69 (dd, 1, J ) 2.0, 8.1), 5.80 (d, 1, J ) 8.1), 5.12
(dd, 1, J ) 9.0, 9.0), 4.94 (ddd, 1, J ) 5.1, 9.0, 9.2), 4.82 (dd, 1,
J ) 6.9, 9.0), 4.39 (d, 1, J ) 6.9), 4.08 (dd, 1, J ) 5.1, 11.6),
3.83 (d, 1, J ) 6.1), 3.32 (dd, 1, J ) 9.2, 11.6), 3.17 (dd, 1, J )
6.1, 18.5), 2.80 (h, 1, J ) 6.9), 2.50-1.25 (series of m, 9), 2.04
(s, 3), 1.99 (s, 3), 1.94 (s, 3), 1.02 (d, 3, J ) 6.9), 0.99 (s, 3),
0.98 (s, 3), 0.95 (d, 3, J ) 6.9); 13C NMR 193.6, 169.9, 169.9,
168.9, 155.1, 146.0, 145.1, 142.2, 137.1, 119.6, 96.8, 71.7, 71.0,
69.2, 62.2, 49.4, 47.0, 38.3, 36.5, 33.5, 28.9, 26.9, 26.6, 23.7,
23.5, 21.5, 21.5, 20.7, 20.7, 20.7, one carbon not observed.
Data for synthetic erinacine A triacetate (42): 9.39 (s, 1),
6.72 (dd, 1, J ) 1.9, 8.2), 5.82 (d, 1, J ) 8.2), 5.08 (dd, 1, J )
8.1, 8.1), 4.87 (dd, 1, J ) 6.4, 8.1), 4.85 (ddd, 1, J ) 5.0, 7.8,
8.1), 4.57 (d, 1, J ) 6.4), 3.96 (dd, 1, J ) 5.0, 11.8), 3.57 (d, 1,
J ) 6.3), 3.31 (dd, 1, J ) 7.8, 11.8), 3.22 (dd, 1, J ) 6.3, 17.8),
2.81 (h, 1, J ) 6.7), 2.53 (br d, 1, J ) 17.8), 2.43-1.24 (series
of m, 8), 2.03 (s, 3), 2.01 (s, 3), 1.99 (s, 3), 1.02 (d, 3, J ) 6.7),
0.98 (s, 3), 0.95 (d, 3, J ) 6.7), 0.93 (s, 3); 13C NMR 193.7,
170.0, 169.7, 169.0, 152.8, 145.1, 145.0, 141.8, 138.5, 120.1,
102.2, 84.9, 71.4, 71.0, 68.7, 61.7, 49.2, 47.7, 38.3, 36.6, 33.0,
28.9, 27.0, 26.9, 26.5, 23.8, 21.5, 21.5, 20.8, 20.7, 20.7. The
1
3
5
2
(1900).
Meth yl (3a r,5a â)-2,3,3a ,4,5,5a ,6,7-Octa h yd r o-3a ,5a -d i-
m eth yl-1-(1-m eth yleth yl)-6-oxocycloh ep t[e]in d en e-8-ca r -
boxyla te (41). A solution containing 35 mg (0.11 mmol) of
4
°
0 and 0.2 mL of Et
C in a sealed tube for 12 h. The solution was cooled, diluted
with Et O, washed with 1 N HCl and brine, dried (MgSO ),
3
N in 5 mL of MeOH was heated at 100
2
4
and concentrated to give 34 mg of nearly pure 41. Further
purification by flash chromatography on silica gel (25:1 hexane/
EtOAc) gave 33 mg (94%) of pure 41 as a yellow oil: 1H NMR
7
.27 (ddd, 1, J ) 0.7, 1.9, 6.3), 5.95 (d, 1, J ) 6.3), 3.86 (d, 1,
J ) 11.0), 3.80 (s, 3), 3.39 (ddd, 1, J ) 1.0, 1.9, 11.0), 2.87 (h,
1
1
3
1
4
1
, J ) 6.9), 2.41 (m, 2), 2.02 (ddd, 1, J ) 4.6, 13.0, 13.0), 1.81-
.57 (m, 4), 1.44 (ddd, 1, J ) 4.0, 4.0, 13.4), 1.17 (s, 3), 1.05 (d,
, J ) 6.9), 1.02 (s, 3), 1.00 (d, 3, J ) 6.9); 13C NMR 205.2,
66.1, 148.7, 144.2, 139.8, 135.8, 123.7, 121.9, 56.9, 52.3, 49.3,
0.6, 38.6, 36.0, 34.2, 28.6, 26.8, 23.8, 22.4, 21.5, 21.5; IR (neat)
715, 1587; UV (EtOH) λmax (ꢀ) 314 nm (9100), 261 nm (5500).
1
13
H and C NMR spectral data are identical to those of an
(
3a r,5a â,6r)-2,3,3a ,4,5,5a ,6,7-Octa h yd r o-6-h yd r oxy-3a ,-
authentic sample.
(+)-Er in a cin e A Dia ster eom er 44 a n d (+)-Er in a cin e A
(4). To 3 mg of each triacetate diastereomer 42 and 43 in 2
5
a -d im e t h yl-1-(1-m e t h yle t h yl)cycloh e p t [e]in d e n e -8-
m eth a n ol. To a solution containing 21 mg (0.064 mmol) of
1 in 10 mL of Et O was added 10 mg (0.26 mmol) of LAH at
78 °C. The reaction was stirred for 10 min at -78 °C and
the solution was warmed to room temperature. The solution
was quenched by the addition of 2 mL of H O, diluted with
Et O, washed with H O and brine, and dried (MgSO ).
4
2
mL of MeOH was added 5 mg of K
stirred at room temperature for 1 h, diluted with 20 mL of
EtOAc, and washed twice with H O. The combined aqueous
2 3
CO . Each solution was
-
2
2
washings were extracted three times with EtOAc and all
organic extracts were combined, washed with brine, and dried
2
2
4
Removal of the solvent under reduced pressure gave 20 mg of
crude diol as a single isomer. Flash chromatography of the
residue on silica gel (5:1 followed by 2:1 hexane/EtOAc) gave
4
(MgSO ). Removal of the solvent under reduced pressure gave
the pure deprotected glycosides 4 and 44 in 90-100% yield.
Further purification was achieved by flash chromatography
on silica gel (EtOAc).
1
7 mg (89%) of pure diol as a clear viscous oil: 1H NMR 6.04
(
dddd, 1, J ) 1.3, 1.3, 2.5, 8.0), 5.59 (d, 1, J ) 8.0), 4.11 (br s,
Data for (+)-erinacine A diastereomer 44: 1H NMR 9.41 (s,
1), 6.80 (dd, 1, J ) 2.3, 8.1), 5.87 (d, 1, J ) 8.1), 4.23 (d, 1, J
) 6.8), 4.02 (dd, 1, J ) 4.9, 11.6), 3.89 (d, 1, J ) 5.9), 3.70 (m,
1), 3.49 (br dd, 1, J ) 9.1, 9.2), 3.30 (dd, 1, J ) 6.2, 18.1), 3.30
(dd, 1, J ) 9.2, 11.6), 3.22 (ddd, 1, J ) 2.4, 6.8, 9.1), 2.87 (m,
1, OH), 2.83 (h, 1, J ) 6.8), 2.54-2.40 (m, 2), 2.40 (m, 2), 2.25
(d, 1, J ) 2.4, OH), 1.76-1.60 (m, 4), 1.33 (ddd, 1, J ) 3.2, 3.7,
13.5), 1.04 (d, 3, J ) 6.8), 1.02 (s, 3), 0.97 (s, 3), 0.96 (d, 3, J )
6.8); 13C NMR 193.9, 155.3, 145.8, 145.8, 142.0, 137.5, 119.6,
99.2, 75.3, 73.1, 69.6, 65.1, 49.3, 47.1, 38.3, 36.4, 33.5, 29.0,
2
2
2
3
1
3
3
), 3.59 (m, 1), 2.83 (h, 1, J ) 6.9), 2.72 (br d, 1, J ) 17.5),
.59 (dd, 1, J ) 5.9, 17.5), 2.46 (ddd, 1, J ) 9.2, 13.7), 2.34 (m,
), 1.75-1.54 (m, 4), 1.24 (ddd, 1, J ) 3.6, 3.6, 12.6), 1.00 (d,
, J ) 6.9), 0.95 (s, 3), 0.94 (d, 3, J ) 6.9), 0.93 (s, 3); 13C NMR
43.8, 143.1, 141.9, 138.0, 121.5, 119.3, 74.5, 68.8, 48.3, 47.2,
8.4, 36.8, 34.1, 32.9, 28.5, 26.7, 26.2, 23.9, 21.6, 21.5; IR (neat)
377, 1596.
Allocya th in B
2
(2). A suspension of 43 mg (0.5 mmol) of
MnO in a solution containing 15 mg (0.05 mmol) of diol in 10
2