Chemistry of zamoranic acid. Part 10. Homochiral hemisynthesis of pereniporin A

Article abstract of DOI:10.1039/a700377c

The synthetic versatility of 12-acetoxydrima-7,9(11)-diene 1 obtained from 15-hydroxylabda-7,13-dien-17-oic acid (zamoranic acid), as a key intermediate in the homochiral semisynthesis of highly functionalized drimanes such as pereniporin A 3, an important antibiotic, through the carbonate 2, is highlighted.

Full text of DOI:10.1039/a700377c

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Chemistry of zamoranic acid. Part 10.† Homochiral hemisynthesis
of pereniporin A
Julio G. Urones,* David Díez, Patricio M. Gómez, Isidro S. Marcos,
Pilar Basabe and Rosalina F. Moro
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de
Salamanca, Plaza de los Caídos 1-5, 37008, Salamanca, Spain
The synthetic versatility of 12-acetoxydrima-7,9(11)-diene 1 obtained from 15-hydroxylabda-7,13-dien-17-
oic acid (zamoranic acid), as a key intermediate in the homochiral semisynthesis of highly functionalized
drimanes such as pereniporin A 3, an important antibiotic, through the carbonate 2, is highlighted.
Introduction
OAc
The drimanes are sesquiterpenes that exhibit a wide range of
biological activities.1 Due to the importance of these properties,
H
much work has been carried out on their synthesis and semisyn-
thesis, using in the latter case a large number of natural prod-
1
ucts.2 For several years we have been studying the transform-
ation of zamoranic acid into active drimanes.3 Zamoranic acid
belongs to the labdane class of sesquiterpenes and was isolated
as the major component from Halimium viscosum.4 It is an ideal
O
HO
precursor 5 for antifeedant drimanes such as polygodial, isol-
ated from Polygonum hydropiper,6 warburganal, isolated from
Warburgia ugandensis,7 or antibiotic drimanes such as pereni-
porin A and B, isolated from the filtered culture of the basidi-
omycete Perenniporia medullaepanis.8 Pereniporin A exhibits
antimicrobial activity against Bacillus subtilis, it inhibits the
root elongation of lettuce and shows cytotoxicity against
O
O
O
OAc
HO
H
H
OH
3
2
Friend leukaemia cells at 130 µg mlϪ1
.
Scheme 1
6. Reduction of the ketone to the required β-hydroxy com-
pound 7 was achieved with DIBAL-H. Any attempt to select-
ively oxidize C-11 to an aldehyde failed, giving in all cases 8
(Scheme 2).
CH2OH
CO2H
CHO
CHO
H
H
OR
OR
R
OH
Polygodial
Zamoranic acid
OR3
OTBDMS
d
O
CHO
OH
H
H
CHO
R2 R1
R2 R1
O
HO
R1
H
R2
H
R3
R
R1
R2
H
H
H
R
R
OH
2
4
5
6
C
O
Ac
7 CH2OH
OH
a
c
e
Pereniporin B
Warburganal
C
O
O
O
O
Ac
8
CHO
O
b
H
H
H
H
H
TBDMS
Results and discussion
Scheme 2 Reagents and conditions: a, CrO3, HOAc, 52%; b, 5% K2CO3
in MeOH, 80%; c, TBDMSCl, DMAP, imidazole, DMF, 77%; d,
DIBAL-H, CH2Cl2, Ϫ78 ЊC, 95%; e, Swern, 34%
Recently we reported the preparation of carbonate 2 from diene
1, which was obtained from 15-hydroxylabda-7,13-dien-17-oic
acid (zamoranic acid).3 It was thought that allylic oxidation at
C-6 of compound 2, carbonate ring-opening and oxidation at
C-11 would lead to an aldehyde that after deprotection of the
hydroxy group at C-12 and cyclization would give pereniporin
A, 3 (Scheme 1).
Because of these results, a new route from 4 was designed.
The selective deprotection of C-12 with retention of the car-
bonate protecting group was achieved via reduction with four
equivalents of NaBH4 in THF–MeOH at 40 ЊC. Under these
conditions diol 9 was obtained (Scheme 2). The reaction of 9
under the usual conditions with TBDMSCl gave only mono-
protected product 10. It was necessary to use TBDMSOTf10 to
obtain compound 11. The selective hydrolysis of the carbonate
rather than the silyl groups was carefully undertaken, the best
conditions being 2  NaOH in dioxane, to give diol 12, a com-
The treatment of 2 with CrO3–HOAc9 gave the required
ketone 4 in an acceptable yield (52%). This ketone was hydro-
lysed to the triol 5 that was selectively protected with tert-
butyldimethylsilyl chloride (TBDMSCl) to give the compound
† For Part 9 in the series, see ref. 3.
J. Chem. Soc., Perkin Trans. 1, 1997
1815

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pound previously reported by Mori and Takaishi.11 After Swern
oxidation of 12 to obtain aldehyde 13, both silyl groups were
removed using TBAF, and the resulting triol cyclized to afford
eriochloroform and referenced to the residual peak of CHCl3 at
1
δ 7.26 and δ 77.0, for H and 13C respectively, in a Bruker WP-
200 SY spectrometer. Chemical shifts are reported in δ(ppm)
and coupling constants (J) are given in Hz. Mass spectra and
accurate mass measurements were recorded on an AEI MS-902
or a VG Micromass 7070E spectrometer. Microanalysis was
carried out using a Perkin-Elmer 2400 CHN Elemental Ana-
lyser. Optical Rotations were determined in a Perkin-Elmer 241
polarimeter in 1 dm cells and are given in units of 10Ϫ1 deg
cm2 gϪ1. Diethyl ether, THF and benzene were distilled from
sodium, and pyridine and dichloromethane were distilled from
calcium hydride under an Ar atmosphere. Ether refers to diethyl
ether.
1
pereniporin A, 3 (Scheme 3). The IR and H NMR spectra of
O
O
OR1
R
O
OH
OTBDMS
4
a
e
H
H
OR2
OTBDMS
R
R1
H
R2
9
H
H
12 CH2OH
13 CHO
Allylic oxidation of 12-acetoxy-9á,11-carbonyldioxydrim-7-ene
2: 12-acetoxy-9á,11-carbonyldioxydrim-7-en-6-one 4
b
c
f
d
10 TBDMS
11 TBDMS
TBDMS
To a stirred solution of 2 (24 mg, 0.07 mmol) in acetic acid (0.7
ml) was added CrO3 (70 mg, 0.7 mmol) at room temperature
and the mixture was stirred for 15 h, then it was diluted with
water (20 ml) and extracted with ether (3 × 20 ml). The com-
bined organic phases were washed with 5% aqueous Na2S2O3,
saturated aqueous NaHCO3 and brine, dried, filtered and evap-
orated. The residue was chromatographed (SiO2, n-hexane–
EtOAc 4:1) yielding 13 mg (52%) of 4, mp 129–130 ЊC (Found:
C, 64.27; H, 7.2. C18H24O6 requires C, 64.27; H, 7.2%); [α]D21
Ϫ62.1 (CHCl3, c 1.56); νmax(film)/cmϪ1 1805, 1745, 1682, 1380,
1222, 1126, 1065; δH 6.15 (1H, s, H-7), 4.87 (1H, d, J 14.0,
HA-12), 4.78 (1H, d, J 14.0, HB-12), 4.48 (2H, s, H-11), 2.73
(1H, s, H-5), 2.13 (3H, s, OCOCH3), 1.18, 1.17, 0.97 (3 × 3H,
3 × s, Me-15, Me-14, Me-13, respectively); δC see Table 1; m/z
336 ([M]ϩ, 6%), 294 (3), 276 (83), 232 (5), 212 (36), 170 (100),
149 (31), 126 (100), 109 (75), 91 (56), 69 (78) [Found: (EI) Mϩ,
336.1572. C18H24O6 requires M, 336.1573].
g
HO
O
HO
H
OH
Pereniporin A, 3
Scheme 3 Reagents and conditions: a, NaBH4, CeCl3, MeOH–THF,
40 ЊC, 82%; b, TBDMSCl, DMAP, imidazole, DMF, 90%; c, TBDMS-
OTf, 2,6-lutidine, CH2Cl2, 0 ЊC, 95%; d, c, 90%; e, 2  NaOH, 1,4-
dioxane, 79%; f, Swern, 93%; g, 1.1  TBAF in THF, 74%
the synthetic material were identical with those of natural
pereniporin A.8a
This semisynthesis of (Ϫ)-pereniporin A in eleven steps from
zamoranic acid, in 4.0% overall yield, demonstrates the
synthetic utility of diene 1.
Hydrolysis of 4: 9á,11,12-trihydroxydrim-7-en-6-one 5
A solution of 3% K2CO3 in MeOH (0.47 ml) was added to
compound 4 (11 mg, 0.033 mmol). The reaction mixture was
stirred at room temperature for 15 min, then water was added
and the mixture extracted with EtOAc, washed with 2  HCl
and water, dried with Na2SO4, filtered and evaporated. The
crude reaction product was chromatographed (SiO2, n-hexane–
EtOAc 1:2) affording 7 mg (80%) of 5 (Found: C, 67.15; H,
9.00. C15H24O4 requires C, 67.14; H, 9.01%); [α]D20 Ϫ62.4
(CH3OH, c 0.94); νmax(film)/cmϪ1 3380, 1660, 1212, 1030, 870;
δH (CDCl3) 5.88 (1H, s, H-7), 4.50 (1H, d, J 13.8, HA-12), 4.30
(1H, d, J 13.8, HB-12), 3.87 (2H, s, H-11), 2.89 (1H, s, H-5),
Experimental
General details
Unless otherwise stated, all chemicals were purchased as the
highest purity commercially available and were used without
further purification. Melting points were determined with a
Kofler hot stage melting point apparatus and are uncorrected.
IR spectra were recorded on a BOMEM 100 FT IR spectro-
photometer. 1H and 13C NMR spectra were performed in deut-
Table 1 13C NMR data, δ(ppm) in CDCl3
C
4
5a
6
7
9a
32.3
19.1
45.4
35.1
10
31.4
18.0
43.9
34.2
46.7
64.8
11
31.5
17.9
44.1
33.9
47.3
65.3
134.0
132.8
87.2
39.6
63.8
66.4
32.0
24.5
17.6
12
32.4
13
33.5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
30.5
17.2
42.1
32.5
58.9
32.6
31.5
18.0
42.5
32.3
56.2
32.5
18.7
44.2
34.2
46.4
65.6
29.0
43.8
33.2
57.2
18.5
44.2
33.8
46.9
65.5
131.0
137.9
75.0
40.2
62.6
67.0
32.7
24.7
18.7
18.1
44.3
34.1
46.5
65.7
130.7
135.8
81.4
41.6
204.9
64.6
32.8
24.7
20.6
b
197.6 203.3 200.8
133.5 126.1 128.4
143.3 161.1 153.6
64.7
136.3 133.8
134.4 134.0
88.9
40.8
64.1
68.0
32.6
25.0
17.9
130.9
139.0
75.2
40.4
62.7
66.9
33.0
25.2
19.1
85.5
44.3
62.8
66.2
33.0
21.4
17.9
153.7
75.9
46.7
61.8
62.6
34.3
22.3
18.6
74.9
44.7
62.1
65.0
33.7
21.9
17.9
86.9
39.6
64.2
66.4
32.2
25.0
18.0
–OCOO–
ButCSi
ButCSi
Me2Si
CH3COO
CH3COO
151.6 152.4
18.5
154.8
18.2 (2)
26.1, 25.9
18.2
25.8
18.3
25.9
18.1 (2)
26.0, 25.7
18.3, 18.2
26.1, 25.9
25.9
Ϫ5.0, Ϫ5.2 Ϫ5.3, Ϫ5.0
Ϫ5.4, Ϫ5.3 Ϫ5.5 (2), Ϫ3.6 (2) Ϫ5.0 (2), Ϫ3.9, Ϫ3.1 Ϫ5.5 (2), Ϫ3.7, Ϫ3.3
170.1
20.5
a
In CD3OD. b Not observed.
1816
J. Chem. Soc., Perkin Trans. 1, 1997

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1.19, 1.15, 0.94 (3 × 3H, 3 × s, Me-15, Me-14, Me-13, respect-
ively); δH (CD3OD) 6.01 (1H, s, H-7), 4.41 (2H, s, H-12), 3.71
(2H, s, H-11), 2.90 (1H, s, H-5), 1.17, 1.11, 1.02 (3 × 3H, 3 × s,
Me-15, Me-14, Me-13, respectively); δC see Table 1; m/z 268
([M]ϩ, 3%), 250 (11), 237 (34), 220 (12), 207 (6), 189 (11), 163
(11), 144 (37), 126 (83), 109 (61), 97 (39), 81 (53), 69 (100)
[Found: (EI) Mϩ, 268.1676. C15H24O4 requires M, 268.1675].
HCl, 5% aqueous NaHCO3 and water, dried (Na2SO4), filtered
and evaporated yielding, after chromatography (SiO2, n-
hexane–EtOAc 19:1), 5 mg (34%) of 8 (Found: C, 66.27; H,
9.52. C21H36O4Si requires C, 66.27; H, 9.58%); νmax(film)/cmϪ1
3380, 1710, 1666, 1460, 1250, 1060, 835; δH 9.92 (1H, s, H-11),
5.96 (1H, s, H-7), 4.20 (2H, s, H-12), 2.83 (1H, s, H-5), 1.29,
1.21, 1.16 (3 × 3H, 3 × s, Me-15, Me-14, Me-13, respectively),
0.89 (9H, s, But), 0.06 (6H, s, Me2Si).
Selective protection of 5: 12-tert-butyldimethylsilyloxy-9á,11-
dihydroxydrim-7-en-6-one 6
Reduction of 4: 9á,11-carbonyldioxydrim-7-ene-6â,12-diol 9
To a solution of 4 (100 mg, 0.30 mmol) and CeCl3 (150 mg, 0.61
mmol) in methanol (3 ml) and THF (3 ml) was added NaBH4
(11 mg, 0.29 mmol) and the mixture warmed to 40 ЊC and
stirred for 20 h, diluted with saturated aqueous NH4Cl (15 ml)
and extracted with ether, washed with brine, dried (Na2SO4),
filtered and evaporated. The residue was chromatographed
(SiO2, n-hexane–EtOAc 1:2) yielding 72 mg (82%) of 9 (Found:
C, 64.88; H, 8.22. C16H24O5 requires C, 64.84; H, 8.16%); [α]D21
Ϫ134.9 (CH3OH, c 0.86); νmax(film)/cmϪ1 3380, 1740, 1260,
1068, 1008, 925; δH (CD3OD) 5.99 (1H, d, J 5.5, H-7), 4.64 (1H,
d, J 9.5, HA-12), 4.40 (1H, m, H-6), 4.36 (1H, d, J 9.5, HB-12),
4.14 (1H, d, J 12.0, HA-11), 4.02 (1H, d, J 12.0, HB-11), 1.20
(3H, s), 0.97 (6H, s); δC see Table 1.
To a solution of the triol 5 (33 mg, 0.12 mmol) in DMF (0.05
ml), catalytic 4-(N,N-dimethylamino)pyridine and imidazole
(34 mg, 0.50 mmol) at room temperature under argon was
added tert-butyldimethylsilyl chloride (23 mg, 0.15 mmol) and
the resulting mixture was stirred for 22 h at room temperature.
Then it was diluted with water, extracted with CH2Cl2, dried,
evaporated and chromatographed (SiO2, n-hexane–EtOAc
19:1) affording 36 mg (77%) of protected alcohol 6 (Found: C,
65.96; H, 9.95. C21H38O4Si requires C, 65.92; H, 10.01%);
νmax(film)/cmϪ1 3440, 1660, 1460, 1255, 1095, 965, 840; δH 5.85
(1H, s, H-7), 4.46 (1H, d, J 13.0, HA-12), 4.36 (1H, d, J 13.0,
HB-12), 3.90–3.60 (3H, m, 2H-11, -OH), 2.84 (1H, s, H-5), 1.21,
1.16, 0.98 (3 × 3H, 3 × s, Me-15, Me-14, Me-13, respectively),
0.93 (9H, s, But), 0.14, 0.13 (2 × 3H, 2 × s, Me2Si); δC see Table
1; m/z 382 ([M]ϩ, 2%), 351 (11), 307 (14), 277 (17), 256 (8), 233
(7), 203 (24), 183 (35), 109 (43), 91 (29), 75 (100) [Found: (EI)
Mϩ, 382.2540. C21H38O4Si requires M, 382.2539].
Protection of 9: 12-tert-butyldimethylsilyloxy-9á,11-carbonyl-
dioxydrim-7-en-6â-ol 10
To a solution of 9 (72 mg, 0.24 mmol) in DMF (50
µl), catalytic 4-(N,N-dimethylamino)pyridine and imidazole (66
mg, 0.97 mmol) at room temperature under argon was added
tert-butyldimethylsilyl chloride (91 mg, 0.61 mmol) and the
resulting mixture stirred for 1 day at room temperature. Then it
was diluted with water, extracted with CH2Cl2, dried, evapor-
ated and chromatographed (SiO2, n-hexane–EtOAc 4:1) afford-
ing 90 mg (90%) of protected alcohol 10 (Found: C, 64.40; H,
9.30. C22H38O5Si requires C, 64.35; H, 9.33%); [α]D20 Ϫ79.2
(CHCl3, c 0.36); νmax(film)/cmϪ1 3500, 1785, 1460, 1380, 1246,
1135, 1060, 835; δH 6.08 (1H, d, J 4.0, H-7), 4.77 (1H, d, J 9.0,
HA-12), 4.56 (1H, m, H-6), 4.33 (1H, d, J 9.0, HB-12), 4.23 (2H,
s, H-11), 1.30 (3H, s), 1.09 (6H, s), 0.90 (9H, s, But), 0.10, 0.09
(2 × 3H, 2 × s, Me2Si); δC see Table 1.
Reduction of 6 with DIBAL-H: 12-tert-butyldimethylsilyloxy-
drim-7-ene-6â,9á,11-triol 7 and 12-tert-butyldimethylsilyloxy-
drim-7-ene-6á,9á,11-triol, C-6 epimer of 7
DIBAL-H (1.5  in toluene; 0.16 ml, 0.24 mmol) was added to
a solution of 6 (21 mg, 0.055 mmol) in dry CH2Cl2 (1 ml) at
Ϫ78 ЊC under argon and the reaction mixture was stirred for 20
min at Ϫ78 ЊC. Water (0.01 ml, 0.55 mmol) was added and the
reaction mixture was warmed to room temperature then dried
with Na2SO4, filtered and evaporated to give, after chroma-
tography (SiO2, n-hexane–EtOAc 9:1), 20 mg (95%) of 7 and
1 mg (5%) of the C-6 epimer of 7.
Compound 7. (Found: C, 65.60; H, 10.52. C21H40O4Si requires
C, 65.58; H, 10.48%); νmax(film)/cmϪ1 3440, 1460, 1250, 1045,
940, 828; δH 5.86 (1H, d, J 5.2, H-7), 4.46 (1H, dd, J 5.2, 4.4, H-
6), 4.35 (1H, d, J 12.7, HA-12), 4.27 (1H, d, J 12.7, HB-12), 3.82
(1H, d, J 10.7, HA-11), 3.63 (1H, d, J 10.7, HB-11), 1.73 (1H, d,
J 4.4, H-5), 1.33, 1.12, 1.07 (3 × 3H, 3 × s, Me-15, Me-14, Me-
13, respectively), 0.91 (9H, s, But), 0.12 (6H, s, Me2Si); δC see
Table 1; m/z 386 ([Mϩ ϩ 2], 14%), 368 (11), 353 (31), 341 (15),
323 (9), 309 (13), 284 (63), 256 (100), 242 (23), 149 (15), 109
(21), 95 (28), 81 (53), 69 (100), 55 (100).
C-6 Epimer of compound 7. (Found: C, 65.57; H, 10.50.
C21H40O4Si requires C, 65.58; H, 10.48%); νmax(film)/ cmϪ1 3340,
1470, 1250, 1215, 1055, 1005, 960, 835; δH 5.73 (1H, s, H-7),
4.37 (1H, d, J 12.0, HA-12), 4.22 (1H, m, H-6), 4.19 (1H, d, J
12.0, HB-12), 3.94 (1H, br s, OH), 3.8–3.6 (2H, m, H-11), 3.48
(1H, br s, OH), 1.70 (1H, d, J 10.3, H-5), 1.26, 1.18, 1.10
(3 × 3H, 3 × s, Me-15, Me-14, Me-13, respectively), 0.91 (9H, s,
But), 0.13, 0.11 (2 × 3H, s, 2 × Me2Si); m/z 386 ([Mϩ ϩ 2], 1%),
353 (32), 291 (16), 261 (10), 235 (15), 187 (47), 161 (18), 105
(52), 75 (100), 69 (59), 55 (59).
Protection of 9: 6â,12-bis(tert-butyldimethylsilyloxy)-9á,11-
carbonyldioxydrim-7-ene 11
To a solution of 9 (17 mg, 0.057 mmol) in CH2Cl2 (0.26 ml) and
2,6-lutidine (2,6-dimethylpyridine) (29 µl, 0.25 mmol) at 0 ЊC
under argon was added tert-butyldimethylsilyl trifluorometh-
anesulfonate (52 µl, 0.228 mmol) and the resulting mixture
stirred for 15 h at room temperature. Then it was diluted with
water, extracted with CH2Cl2, dried, evaporated and chromato-
graphed (SiO2, n-hexane–EtOAc 19:1) affording 27 mg (90%)
of diprotected alcohol 11 (Found: C, 64.00; H, 10.52.
C28H52O5Si2 requires C, 64.07; H, 9.99%); [α]D22 Ϫ116.3 (CHCl3,
c 1.24); νmax(film)/cmϪ1 1810, 1470, 1260, 1232, 1115, 960, 840;
δH 6.04 (1H, d, J 4.7, H-7), 4.70 (1H, d, J 9.5, HA-12), 4.54 (1H,
m, H-6), 4.32 (1H, d, J 9.5, HB-12), 4.23 (1H, d, J 12.0, HA-11),
4.13 (1H, d, J 12.0, HB-11), 1.24, 1.10, 1.03 (3 × 3H, 3 × s,
Me-15, Me-14, Me-13, respectively), 0.90, 0.88 (2 × 9H, 2 × s,
But), 0.14 (6H, s, Me2Si), 0.09 (6H, s, Me2Si); δC see Table 1.
Hydrolysis of 11: 6â,12-bis(tert-butyldimethylsilyloxy)drim-7-
ene-9á,11-diol 12
Swern oxidation of 7: 12-tert-butyldimethylsilyloxy-9á-hydroxy-
6-oxodrim-7-en-11-al 8
Aqueous 2  NaOH (0.22 ml) was added to 11 (12 mg, 0.023
mmol) in 1,4-dioxane (0.41 ml) and stirred at room temper-
ature for 2 h. The reaction mixture was extracted with ether,
washed with 2  HCl and water. The combined organic layers
were dried (Na2SO4), filtered and evaporated. The residue was
chromatographed (SiO2, n-hexane–EtOAc 49:1) affording 4 mg
(33%) of starting material 11 and 6 mg (79% of the transformed
11) of 12. [α]D22 Ϫ102.3 (CHCl3, c 0.6) (Found: C, 65.40; H, 10.43.
C27H54O4Si2 requires C, 65.00; H, 10.91%); νmax(film)/cmϪ1
Oxalyl chloride (3.5 µl, 0.04 mmol) in CH2Cl2 (0.1 ml) was
cooled to Ϫ60 ЊC. A solution of DMSO (6 µl, 0.08 mmol) in
CH2Cl2 (0.1 ml) was slowly added over a 5 min period. A solu-
tion of 7 (15 mg, 0.039 mmol) in CH2Cl2 (0.2 ml) was added
dropwise and stirred for 50 min at Ϫ60 ЊC. Triethylamine (27 µl,
0.19 mmol) was added and the reaction kept at Ϫ60 ЊC for 5
min, warmed to room temperature and then quenched with
water, extracted with ether and washed successively with 0.5 
J. Chem. Soc., Perkin Trans. 1, 1997
1817

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3480–3200, 1460, 1250, 1110, 1075, 970, 840; δH 5.73 (1H, d, J
5.2, H-7), 4.46 (1H, t, J 5, H-6), 4.35 (1H, d, J 12.0, HA-12),
4.17 (1H, d, J 12.0, HB-12), 3.80–3.60 (2H, m, H-11), 3.40 (1H,
s, -OH), 1.23, 1.09, 0.99 (3 × 3H, 3 × s, Me-15, Me-14, Me-13,
respectively), 0.89, 0.86 (2 × 9H, 2 × s, But), 0.10 (12H, s,
2 × Me2Si); δC see Table 1.
1390, 1365, 1130, 1090, 1050, 1030, 1010, 915, 865;
δH (CD3OD) 5.69 (1H, ddd, J 4.0, 2.0, 1.5, H-7), 5.35 (1H, s,
H-11), 4.58 (1H, dt, J 12.5, 2.0, HA-12), 4.50 (1H, m, H-6), 4.21
(1H, dt, J 12.5, 1.5, HB-12), 1.39, 1.19, 1.13 (3 × 3H, 3 × s,
Me-15, Me-14, Me-13, respectively).
Acknowledgements
Swern oxidation of 12: 6â,12-bis(tert-butyldimethylsilyloxy)-9á-
hydroxydrim-7-en-11-al 13
The authors thank the Universidad de Salamanca, Spain, for a
doctoral fellowship to P. M. G. and the Junta de Castilla y León
for financial support.
Oxalyl chloride (3 µl, 0.04 mmol) in CH2Cl2 (0.2 ml) was cooled
at Ϫ60 ЊC. A solution of DMSO (6 µl, 0.08 mmol) in CH2Cl2 (0.2
ml) was slowly added over a 5 min period. A solution of 12 (6.5
mg, 0.013 mmol) in CH2Cl2 (0.4 ml) was added dropwise and
the mixture stirred for 1 h at Ϫ60 ЊC. Triethylamine (18
µl, 0.13 mmol) was added and the reaction kept at Ϫ60 ЊC for 5
min, warmed to room temperature and quenched with water
and extracted with ether. The combined extracts were washed
successively with 0.5  HCl, 5% aqueous NaHCO3 and water,
dried, filtered and evaporated yielding, after chromatography
(SiO2, n-hexane–EtOAc 49:1), 6 mg (93%) of 13 (Found: C,
65.28; H, 10.53. C27H52O4Si2 requires C, 65.27; H, 10.55%);
νmax(film)/cmϪ1 3460, 1715, 1460, 1255, 1070, 955, 835; δH 9.86
(1H, s, H-11), 5.91 (1H, d, J 5.2, H-7), 4.51 (1H, m, H-6), 4.06
(1H, d, J 11.7, HA-12), 3.96 (1H, d, J 11.7, HB-12), 1.42, 1.24,
1.00 (3 × 3H, 3 × s, Me-15, Me-14, Me-13, respectively), 0.89,
0.86 (2 × 9H, 2 × s, But), 0.13 (6H, s, Me2Si), 0.02 (3H, s, MeSi),
0.01 (3H, s, MeSi); δC see Table 1.
References
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1845 and references cited therein.
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Deprotection of 13: pereniporin A 3
Dry tetra-n-butylammonium fluoride (1.1  solution in THF;
0.35 ml, 0.39 mmol) was added to 13 (6 mg, 0.012 mmol) at
room temperature and the mixture was stirred for 4 h at 50 ЊC
and then for 1 day at room temperature. The mixture was
poured into water (1 ml) and extracted with ethyl acetate. The
organic layers were combined and washed with brine, dried over
Na2SO4, filtered and evaporated under reduced pressure. The
residue was chromatographed (SiO2, n-hexane–EtOAc 7:3)
affording 2.4 mg (74%) of 3, [α]D22 Ϫ170.5 (MeOH, c 0.24);
νmax(film)/cmϪ1 3450, 3430, 3390, 2980, 2940, 2900, 1465, 1425,
Paper 7/00377C
Received 15th January 1997
Accepted 18th March 1997
1818
J. Chem. Soc., Perkin Trans. 1, 1997