Cascade radical cyclisations leading to polycyclic diterpenes. Total synthesis of (±)-spongian-16-one

Article abstract of DOI:10.1039/a708042e

A cascade of three consecutive 6-endo-trig radical cyclisations from the polyene acyl radical intermediate 12 derived from the selenoate 11 is used to construct the trans,anti,trans,anti,cis-tetracyclic keto lactone 20 in one step. Manipulation of the ketone function in 20 to the corresponding gem-dimethyl substituted carbon then completed a concise synthesis of the marine metabolite spongian-16-one 1.

Full text of DOI:10.1039/a708042e

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Cascade radical cyclisations leading to polycyclic diterpenes.
Total synthesis of ( )-spongian-16-one
Gerald Pattenden,* Lee Roberts and Alexander J. Blake
Department of Chemistry, Nottingham University, Nottingham, UK NG7 2RD
A cascade of three consecutive 6-endo-trig radical cyclisations from the polyene acyl radical intermediate
12 derived from the selenoate 11 is used to construct the trans,anti,trans,anti,cis-tetracyclic keto lactone 20
in one step. Manipulation of the ketone function in 20 to the corresponding gem-dimethyl substituted
carbon then completed a concise synthesis of the marine metabolite spongian-16-one 1.
A wide variety of oxygenated tetracyclic diterpenes have been
isolated from the marine sponge order Dictyoceratida, and
several of these metabolites show antimicrobial activity, whilst
others have been found to exhibit activity against Herpes sim-
plex virus, type 1, and P388 murine leukemia cells. Represen-
tative members of this family of diterpenes include: spongian-
16-one 1 and spongiandiyl acetate 21 isolated from Dictyoden-
drilla cavernosa2 and Chelonaplysilla violacea3 found off the
coasts of Australia and New Zealand; the spongianenones 3
and 4 produced by the Canary Island sponge Spongia
officinalis;4 and the furanoditerpenes spongiadiol 5 and iso-
spongiadiol 6 isolated from the deep water Caribbean sponge
Spongia linnaeus.5
nature elaborates the steroid ring system, via enzyme-mediated
electrophilic cyclisation of squalene oxide, the carbocyclic
backbones in the metabolites 1–6 are produced in nature via
electrophilic cyclisation of a preorganised geranylgeraniol sub-
strate, as indicated in 7→8 (Scheme 1). In several earlier publi-
cations8 we have developed the idea of elaborating linear and
angular six-membered fused carbocycles from polyene acyl rad-
ical precursors via consecutive 6-endo-trig modes of cyclisation,
viz 9→10 (Scheme 2).7 We have also applied this strategy in the
•
•
In spite of their interesting biological properties, until quite
recently very few synthetic studies amongst this class of com-
pound had been described.6,7 In a similar manner to the way
O
O
9
10
Scheme 2
O
OAc
O
synthesis of several steroidal ring systems, including aza-
steroids,9 and applied it in a concise total synthesis of ( )-
spongian-16-one 1.10 This paper describes the full details of this
total synthesis.
H
H
O
H
H
H
H
OAc
The overall strategy we followed for the total synthesis of
spongian-16-one 1 is shown in Scheme 3 and was based on
elaboration of the butenolide substituted polyene selenoate
11, followed by serial 6-endo-trig radical cyclisation from the
intermediate acyl radical 12 and manipulation of the ketone
functionality in the product 13. At the outset of our synthetic
work, although we were confident that the cascade cyclisation
12→13 would produce the required trans,anti,trans,anti-
stereochemistry for the A,B,C-ring system in the tetracyclic
ketone 13, we were less sure of the outcome of the ring C/D
stereochemistry in this product; we argued however that this
particular cyclisation would most likely lead ultimately to the
thermodynamically more stable (natural) cis-C/D ring junction
stereochemistry.
H
H
1
2
O
O
O
AcO
HO
O
H
H
H
H
OH
H
H
3
4
The butenolide substituted polyene selenoate 11 was pre-
pared from the known (E)-bromo alcohol11 14a as shown in
Scheme 4. Thus, protection of the bromo alcohol as its tetra-
hydropyranyl ether 14b followed by lithiation and reaction with
cyclopropyl methyl ketone,12 first led to the substituted cyclo-
propylmethanol 15 in 80% yield. Treatment of 15 with 48%
HBr at Ϫ20 ЊC, according to the procedure of Julia et al.,13
resulted in ring-opening of the cyclopropane and formation of
O
O
O
HO
O
H
H
HO
H
H
5
6
OH
OH
+
Enz
H
OH
OH
1–6
7
8
Enz
H
Scheme 1
J. Chem. Soc., Perkin Trans. 1, 1998
863

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O
O
O
H
H
O
O
O
1
H
•
H
PhSe
O
O
O
11
12
13
Scheme 3
R′
OH
ii
iii
Br
OR
THPO
OR
14
15
16
a R = H
b R = THP
a R = H; R′ = Br
b R = THP; R′ = Br
c R = THP; R′ = I
i
i
iv
v
O
O
O
PhS
vii, viii
x
vi
O
O
11
O
R
THPO
THPO
O
18
17
19
a R = H
b R = OH
ix
Scheme 4 Reagents: i, DHP, PPTS, 25 ЊC (95%); ii, Li, THF, 0 ЊC, methyl cyclopropyl ketone (80%); iii, 48% HBr, Ϫ20 ЊC (86%); iv, NaI, Me2CO,
25 ЊC (89%); v, 2-phenylthiobutyrolactone, LDA, HMPA, Ϫ78 ЊC (71%); vi, MCPBA, Ϫ78 ЊC to 0 ЊC, then ∆, C6H5Me, CaCO3 (∼80%); vii, PPTS,
EtOH, 55 ЊC (94%); viii, Dess–Martin periodinane (89%); ix, NaH2PO4, ButOH, H2O, NaClO2, 2-methylbut-2-ene (82%); x, N-phenylseleno-
phthalimide, Bu3P, Ϫ30 ЊC (86%)
sequential oxidation of the resulting alcohol using Dess–
Martin periodinane and sodium chlorite next led to the carb-
oxylic acid 19b, which was finally converted into the selenoate
11 in 86% yield using N-phenylselenophthalimide–tributyl-
phosphine.16
When a solution of the selenoate 11 in dry degassed benzene
was heated to reflux and treated dropwise over 8 h with a solu-
tion of Bu3SnH and AIBN in benzene,8 work-up and chrom-
atography gave the tetracyclic keto lactone 20 as colourless
needles, mp 178–180 ЊC, in 53% yield. The trans,anti,trans,anti,
cis-stereochemistry assigned to this tetracycle resulting from
the cascade of three consecutive 6-endo-trig radical cyclisations
from the acyl radical intermediate 12 followed from analysis of
its 13C NMR spectroscopic data and comparison of these data
with those of previously produced polycycles from our earlier
work.8 The geometry was also confirmed by X-ray crystallo-
graphic analysis (Fig. 1). A small amount of a minor diastereo-
isomer of the structure 20 was separated by chromatography
and the spectroscopic data for this compound support the
Fig. 1 X-Ray structure of tetracyclic keto lactone 20
cis,anti,trans,anti,cis-stereochemistry shown in 21;† it is pos-
sible that this isomer is produced as a result of specific epimer-
isation of the C5 centre in 20, either during the reaction or
during chromatographic purification rather than during the
the (E)-homoallylic bromide 16b accompanied by smaller
amounts of the deprotected bromide 16a, which could be repro-
tected leading to 16b in an overall 80% yield. The (E)-homo-
cascade radical cyclisation.
allylic bromide 16b was next converted into the corresponding
With the complete tetracyclic core 20 of spongian-16-one
iodide 16c, under Finkelstein conditions, which was then used
now available, with the correct trans,anti,trans,anti,cis-stereo-
to alkylate the lithium enolate derived from 2-phenylthio-
chemistry, all that was needed to complete the total synthesis of
butyrolactone14 leading to the substituted butyrolactone 17.
Oxidation of 17 with m-chloroperbenzoic acid led to the corre-
sponding sulfoxide which readily eliminated the elements of
† This stereochemistry follows from inspection and comparison of
phenylsulfinic acid on heating in toluene for 3 h,15 producing
NMR data with model compounds prepared during these studies and
in earlier work.8
the butenolide 18 in 61% yield. Deprotection of 18, followed by
864
J. Chem. Soc., Perkin Trans. 1, 1998

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( )-1 was to manipulate the ring A ketone function in 20 to the
corresponding gem-dimethyl substituted carbon. This conver-
sion was readily accomplished following methylenation of 20
using Lombardo’s conditions,17 leading to 22, then Simmons–
Smith cyclopropanation of 22 to the corresponding cyclo-
propane 23, and finally hydrogenolysis18 of 23 (Scheme 5). The
cm3). The combined organic extracts were dried (MgSO4) and
then evaporated in vacuo. Chromatography of the residue on
silica using ethyl acetate–light petroleum (bp 40–60 ЊC) (1:4)
as eluent gave the alcohol (2.8 g, 80%) as a colourless oil;
νmax(film)/cmϪ1 3454 and 1654; δH(250 MHz, CDCl3) 5.16 (1H,
br t, J ∼6.7 Hz, ᎐CH᎐), 4.57 (1H, br s, CH CHO ), 3.91–3.83
᎐
2
2
(1H, m), 3.76–3.72 (1H, m), 3.53–3.43 (1H, m), 3.41–3.35 (1H,
m), 2.16–1.98 (4H, m), 1.73–1.48 (12H, m), 1.59 (3H, s, Me),
1.12 (3H, s, Me), 0.91 (1H, d, J 6.4 Hz) and 0.39–0.32 (4H, m,
2 × ϪCH2); δC(67.8 MHz, CDCl3) 135.1 (s), 124.6 (d), 98.7 (d),
71.0 (s), 67.5, 62.2, 42.9, 39.3, 30.7, 29.2, 25.8, 25.4, 24.4, 22.6,
20.9, 19.6, 15.8, 0.5 (t) and 0.4 (t); m/z (EI) 208.1822 (Mϩ Ϫ
THPOH, C14H24O requires 208.1827).
O
O
H
H
Bu3SnH
AlBN
O
O
+
11
H
H
H
H
H
H
O
O
20
21
(E,E)-2-[(12-Bromo-5,9-dimethyldodeca-5,9-dienyl)oxy]tetra-
hydro-2H-pyran 16b
i
The alcohol 15 (2.75 g, 8.86 mmol) was added dropwise over
5 min to vigorously stirred 48% HBr (5 cm3) at Ϫ20 ЊC.13 The
mixture was stirred for a further 1 h at this temperature and
then diluted with diethyl ether (100 cm3) and water (50 cm3).
The organic layer was washed with saturated aqueous sodium
hydrogen carbonate (50 cm3) and brine (50 cm3), and then both
of the separated aqueous phases were extracted with diethyl
ether (2 × 100 cm3). The combined organic extracts were dried
(MgSO4) and then evaporated in vacuo. Chromatography of the
residue on silica gel using ethyl acetate–light petroleum (bp 40–
60 ЊC) (1:9 to 1:4) as eluent gave (i) the tetrahydropyran
homoallylic bromide (eluted first) (2.0 g, 59%) as a colourless oil
(Found: C, 61.4; H, 9.1. C19H33BrO2 requires C, 61.1; H, 8.9%);
νmax(film)/cmϪ1 1661; δH(250 MHz, CDCl3) 5.15–5.10 (2H, m,
O
O
H
H
H
H
ii
iii
O
O
1
H
H
H
H
22
23
Scheme 5 Reagents: i, Zn, TiCl4, CH2Br2, 0 ЊC (79%); ii, CH2I2,
Zn(Cu), Et2O (95%); iii, PtO2, H2, HOAc, 25 ЊC (80%)
synthetic ( )-spongianone was obtained as colourless crystals,
and had 1H and 13C NMR spectroscopic data which were super-
imposable on those recorded for the natural product isolated
from D. cavernosa.2,19
2 × ᎐CH᎐), 4.57 (1H, br s, CH CHO ), 3.87–3.82 (1H, m),
᎐
2
2
3.75–3.71 (1H, m), 3.51–3.46 (1H, m), 3.40–3.29 (3H, m), 2.61–
2.55 (2H, m), 2.10–1.97 (4H, m), 1.84–1.45 (12H, m), 1.62 (3H,
s, Me) and 1.58 (3H, s, Me); δC(67.8 MHz, CDCl3) 138.5 (s),
135.1 (s), 124.0 (d), 120.8 (d), 98.8 (d), 67.5 (t), 62.3 (t), 39.6 (t),
39.4 (t), 32.8 (t), 31.7 (t), 30.7 (t), 29.2 (t), 26.3 (t), 25.5 (t), 24.5
(t), 19.7 (t), 16.2 (q) and 15.8 (q); and (ii) the alcohol 16a (eluted
second) (688 mg, 27%) as a colourless oil; νmax(film)/cmϪ1 3356
Experimental
For general experimental details, see ref. 8.
(E)-2-[(8-Bromo-5-methyloct-5-enyl)oxy]tetrahydro-2H-pyran
14b
and 1653; δ (250 MHz, CDCl ) 5.16–5.10 (2H, m, 2 × ᎐CH᎐),
᎐
H
3
A solution of 8-bromo-5-methyloct-5-en-1-ol11 (2.60 g, 11.8
mmol), dihydropyran (1.61 cm3, 1.48 g, 17.6 mmol) and pyrid-
inium toluene-p-sulfonate (297 mg, 1.18 mmol) in dichloro-
methane (35 cm3) was stirred at room temperature for 4 h. The
solution was diluted with diethyl ether (150 cm3) and then
washed with 1:1 saturated brine–water (50 cm3). The organic
phase was dried (MgSO4) and then evaporated in vacuo. Chro-
matography of the residue on silica gel using ethyl acetate–light
petroleum (bp 40–60 ЊC) (1:19) as eluent gave the tetrahydro-
pyran (3.4 g, 95%) as a colourless oil; νmax(film)/cmϪ1 1654;
3.89–3.82 (2H, m, CH2OH), 3.37–3.30 (2H, m, CH2Br), 2.61–
2.53 (2H, m), 2.11–2.00 (6H, m), 1.71–1.41 (4H, m), 1.63 (3H, s,
Me) and 1.59 (3H, s, Me); δC(67.8 MHz, CDCl3) 138.5 (s), 135.0
(s), 124.1 (d), 120.9 (d), 62.9 (t), 39.6 (t), 39.3 (t), 32.9 (t), 32.3
(t), 31.6 (t), 26.3 (t), 24.0 (t), 16.2 (q) and 15.8 (q); m/z (EI)
208.1835 (Mϩ Ϫ HBr, C14H24O requires 208.1827). The alcohol
16a was reprotected using the following procedure: a solution
of the alcohol (688 mg, 2.38 mmol), dihydropyran (326 µl, 300
mg, 3.57 mmol) and pyridinium toluene-p-sulfonate (60 mg,
0.238 mmol) in dichloromethane (10 cm3) was stirred at room
temperature for 18 h. The reaction was diluted with diethyl
ether (100 cm3) and then washed with 1:1 saturated brine–
water (50 cm3). The separated aqueous layer was extracted with
diethyl ether (75 cm3) and the combined organic extracts were
dried (MgSO4) and then evaporated in vacuo. Chromatography
of the residue on silica gel using ethyl acetate–light petroleum
(bp 40–60 ЊC) (1:9) as eluent gave the tetrahydropyran 16b (751
mg, 85%) as a colourless oil.
δ (270 MHz, CDCl ) 5.16–5.10 (1H, m, ᎐CH᎐), 4.57 (1H, br s,
᎐
H
3
CH2CHO2), 3.89–3.82 (1H, m), 3.77–3.69 (1H, m), 3.51–3.29
(4H, m), 2.60–2.52 (2H, m), 2.08–1.99 (2H, m), 1.84–1.53
(10H, m) and 1.70 (3H, s, Me); δC(67.8 MHz, CDCl3) 138.5 (s),
120.9 (d), 98.8 (d), 67.4 (t), 62.3 (t), 39.3 (t), 32.8 (t), 31.6 (t),
30.7 (t), 29.2 (t), 25.4 (t), 24.3 (t), 19.6 (t) and 16.0 (q); m/z (EI)
202.0354 (Mϩ Ϫ THPOH, C9H15Br requires 202.0357).
(E)-2-[(9-Cyclopropyl-9-hydroxy-5-methyldec-5-enyl)oxy]tetra-
hydro-2H-pyran 15
(E,E)-2-[(5,9-Dimethyl-12-iodododeca-5,9-dienyl)oxy]tetra-
hydro-2H-pyran 16c
One third of a solution of the bromide 14b (3.38 g, 11.1 mmol)
and methyl cyclopropyl ketone12 (3.30 cm3, 2.79 g, 33.2 mmol)
in THF (13 cm3) was added to lithium wire (1 mm) (461 mg,
66.4 mmol) under THF (57 cm3) in an atmosphere of argon at
0 ЊC. The remainder of the solution was added over 25 min and
the mixture was then stirred at 0 ЊC for 4 h. Excess lithium was
removed with tweezers and the reaction was then diluted with
diethyl ether (150 cm3). The mixture was washed with saturated
aqueous ammonium chloride (75 cm3) and saturated aqueous
sodium hydrogen carbonate (75 cm3), and then each of the
separated aqueous phases was extracted with diethyl ether (100
A mixture of the bromide 16b (2.84 g, 7.61 mmol) and sodium
iodide (2.85 g, 19.0 mmol) in acetone (25 cm3) was stirred at
room temperature for 48 h. The solvent was removed in vacuo
and the residue was then partitioned between diethyl ether (100
cm3) and water (50 cm3). The separated diethyl ether layer
was washed with saturated aqueous sodium thiosulfate (25 cm3)
and brine (25 cm3) and then each of the aqueous layers was
extracted with diethyl ether (75 cm3). The combined organic
extracts were dried (MgSO4) and then evaporated in vacuo.
Chromatography of the residue on silica gel using ethyl acetate–
J. Chem. Soc., Perkin Trans. 1, 1998
865

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light petroleum (bp 40–60 ЊC) (1:9) as eluent gave the iodide
(2.8 g, 89%) as a pale yellow oil; νmax(film)/cmϪ1 1654; δH(400
25.8 (t), 25.7 (t), 24.8 (t), 20.0 (t), 16.4 (q) and 16.1 (q); m/z (EI)
274.1939 (Mϩ Ϫ THPOH, C18H26O2 requires 274.1933).
MHz, CDCl ) 5.11 (2H, m, 2 × ᎐CH᎐), 4.59 (1H, br s,
᎐
3
CH2CHO2), 3.90–3.85 (1H, m), 3.75–3.71 (1H, m), 3.52–3.50
(1H, m), 3.40–3.38 (1H, m), 3.14–3.08 (2H, m), 2.62–2.58 (2H,
m), 2.10–1.96 (8H, m), 1.85–1.46 (8H, m), 1.61 (3H, s, Me) and
1.60 (3H, s, Me); δC(67.8 MHz, CDCl3) 138.0 (s), 135.0 (s),
124.0 (d), 122.9 (d), 98.7 (d), 67.4 (t), 62.2 (t), 39.5 (t), 39.3 (t),
30.7 (t), 29.2 (t), 26.2 (t), 25.4 (t), 24.2 (t), 22.3 (t), 19.6 (t), 16.2
(q), 15.8 (q) and 6.0 (t); m/z (EI) 420.1522 (Mϩ, C19H33IO2
requires 420.1525).
(E,E)-3-(4,8-Dimethyl-12-oxododeca-3,7-dienyl)furan-2(5H)-
one 19a
(a) Pyridinium toluene-p-sulfonate (60 mg, 0.238 mmol) was
added to a solution of the furanone 18 (896 mg, 2.38 mmol) in
ethanol (19 cm3), and the mixture was then warmed to 55 ЊC for
4 h. The mixture was cooled and then evaporated in vacuo.
Chromatography of the residue on silica gel using ethyl acetate–
light petroleum (bp 40–60 ЊC) (1:1) as eluent gave (E,E)-3-(4,8-
dimethyl-12-hydroxydodeca-3,7-dienyl)furan-2(5H)-one (610
mg, 88%) as a colourless oil; νmax(film)/cmϪ1 3426, 1748 and
(E,E)-4,5-Dihydro-3-[4,8-dimethyl-12-[(tetrahydro-2H-pyran-2-
yl)oxy]dodeca-3,7-dienyl]-3-phenylthiofuran-2(3H)-one 17
1650; δ (250 MHz, CDCl ) 7.12 (1H, t, J 1.8 Hz, ᎐CH᎐), 5.12
᎐
H
3
n-Butyllithium (8.94 cm3, 14.3 mmol, 1.6  in hexanes) was
added to a solution of diisopropylamine (2.51 cm3, 1.81 g, 17.9
mmol) in THF (25 cm3) cooled to 0 ЊC. After 15 min the solu-
tion was cooled to Ϫ78 ЊC, where it was stirred for a further 15
min and then 2-phenylthiobutyrolactone14 (2.31 g, 11.9 mmol)
in THF (10 cm3) was added dropwise over 30 min. The mixture
was allowed to warm to Ϫ50 ЊC over 2 h. The reaction was
recooled to Ϫ78 ЊC and then a solution of the iodide 16c (2.51
g, 5.98 mmol) and HMPA (2.08 cm3, 2.14 g, 11.9 mmol) in THF
(10 cm3) was added dropwise over 5 min. The mixture was
stirred at Ϫ78 ЊC for 1 h and then allowed to warm to room
temperature overnight when it was diluted with diethyl ether
(150 cm3) and water (50 cm3). The separated ethereal layer was
washed with brine (50 cm3) and both aqueous phases were then
extracted with diethyl ether (100 cm3). The combined organic
extracts were dried (MgSO4) and then evaporated in vacuo.
Chromatography of the residue on silica gel using ethyl acetate–
light petroleum (bp 40–60 ЊC) as eluent (1:4) gave the dihydro-
furanone (2.1 g, 71%) as a colourless oil; νmax(film)/cmϪ1 1769
and 1669; δH(250 MHz, CDCl3) 7.56–7.54 (2H, m, 2 × aryl-H),
(2H, m, 2 × ᎐CH᎐), 4.78 (2H, d, J 1.8 Hz, CH O), 3.86 (2H, t,
᎐
2
J 6.5 Hz, CH2OH), 2.33–2.26 (4H, m), 2.09–1.95 (6H, m), 1.69–
1.39 (4H, m) and 1.61 (6H, s, 2 × Me); δC(67.8 MHz, CDCl3)
174.7 (s), 144.3 (d), 136.5 (s), 135.1 (s), 134.0 (s), 124.2 (d), 122.7
(d), 70.1 (t), 62.9 (t), 39.6 (t), 39.3 (t), 32.3 (t), 26.4 (t), 25.6 (t),
25.4 (t), 24.0 (t), 16.0 (q) and 15.8 (q); m/z (EI) 292.2060 (Mϩ,
C18H28O3 requires 292.2039).
(b) Dess–Martin periodinane (1.09 g, 2.56 mmol) was added
portionwise over 5 min to a stirred solution of the alcohol from
(a) (500 mg, 1.71 mmol) in dichloromethane (15 cm3) at room
temperature. The mixture was stirred at room temperature for
1 h, then diluted with diethyl ether (40 cm3) and stirred with a
solution of sodium hydrogen carbonate (1 g) and sodium thio-
sulfate (3.25 g) in water (50 cm3) for 30 min until two layers had
formed. The separated ethereal layer was washed with brine (50
cm3), and both aqueous layers were then extracted with diethyl
ether (2 × 50 cm3). The combined organic extracts were dried
(MgSO4) and then evaporated in vacuo. Chromatography of the
residue on silica gel using ethyl acetate–light petroleum (bp 40–
60 ЊC) (1:2) as eluent gave the aldehyde (436 mg, 89%) as a
colourless oil; νmax(film)/cmϪ1 1754, 1722 and 1652; δH(250
MHz, CDCl3) 9.76 (1H, t, J 1.7 Hz, CHO), 7.11 (1H, br s,
7.44–7.33 (3H, m, 3 × aryl-H), 5.09 (2H, m, 2 × ᎐CH᎐), 4.58
᎐
(1H, br s, CH2CHO2), 4.26–4.22 (2H, m, CH2O), 3.92–3.86
(1H, m), 3.75–3.74 (1H, m), 3.51–3.48 (1H, m), 3.40–3.38 (1H,
m), 2.50–2.20 (6H, m), 2.06–1.40 (16H, m) and 1.61 (6H, s,
2 × Me); δC(67.8 MHz, CDCl3) 176.1, 137.0, 136.4, 135.0,
129.4, 128.9, 127.5, 124.1, 122.5, 98.8, 67.5, 64.9, 62.3, 53.9,
39.6, 39.4, 34.6, 34.3, 30.7, 29.2, 26.4, 25.4, 24.5, 23.1, 19.7, 16.1
and 15.8; m/z (ES) 509.2667 (Mϩ ϩ Na, C29H42O4SNa requires
509.2701).
᎐CH᎐), 5.13–5.09 (2H, m, 2 × ᎐CH᎐), 4.77 (2H, m, CH O),
᎐
᎐
2
2.42–2.25 (6H, m), 2.08–1.97 (6H, m), 1.76–1.67 (2H, m), 1.60
(3H, s, Me) and 1.58 (3H, s, Me); δC(67.8 MHz, CDCl3) 203.1
(s), 174.5 (s), 144.7 (d), 136.8 (s), 134.3 (s), 134.2 (s), 125.6 (d),
123.1 (d), 70.4 (t), 43.5 (t), 39.8 (t), 39.1 (t), 26.8 (t), 26.0 (t),
25.8 (t), 20.5 (t), 16.4 (q) and 16.0 (q); m/z (EI) 290.1883 (Mϩ,
C18H26O3 requires 290.1882).
(E,E)-3-[4,8-Dimethyl-12-[(tetrahydro-2H-pyran-2-yl)oxy]-
dodeca-3,7-dienyl]furan-2(5H)-one 18
(E,E)-5,9-Dimethyl-12-(2-oxo-5H-furan-3-yl)dodeca-5,9-dienoic
acid 19b
m-Chloroperoxybenzoic acid (962 mg, 4.74 mmol, 85%) was
added in one portion to a solution of the thioether 17 (1.92 g,
3.95 mmol) in dichloromethane (20 cm3) at Ϫ78 ЊC. The stirred
mixture was allowed to warm to 0 ЊC over 3 h and then diethyl
ether (125 cm3) was added. The resulting solution was washed
with a mixture of saturated aqueous sodium thiosulfate (50
cm3) and saturated aqueous sodium hydrogen carbonate (150
cm3), and the separated organic layer was then dried (MgSO4)
and evaporated in vacuo. The crude product was dissolved in
toluene (20 cm3) and solid calcium carbonate (1.0 g) was then
added. The reaction was heated under reflux for 3 h, then
cooled, filtered through Florisil, and evaporated in vacuo.
Chromatography of the residue on silica gel using ethyl acetate–
light petroleum (bp 40–60 ЊC) (1:4) as eluent gave (i) recovered
starting material (eluted first) (410 mg, 23%), and (ii) the
furanone (eluted second) (912 mg, 61%) as a colourless oil;
A solution of sodium chlorite (1.75 g, 15.4 mmol, 80% tech) in
water (7.4 cm3) was added to a vigorously stirred mixture of the
aldehyde 19a (430 mg, 1.48 mmol) and sodium dihydrogen
phosphate (1.75 g, 11.2 mmol) in tert-butyl alcohol (36 cm3),
2-methylbut-2-ene (7.4 cm3) and water (7.4 cm3) at room tem-
perature. The mixture was stirred at room temperature for 5 h,
and then evaporated in vacuo. The residue was partitioned
between ethyl acetate (50 cm3) and water (10 cm3), and then the
aqueous layer was extracted with ethyl acetate (2 × 50 cm3). The
combined organic extracts were washed with brine (35 cm3)
then dried (MgSO4) and evaporated in vacuo to leave the acid
(370 mg, 82%) as a colourless oil; νmax(film)/cmϪ1 3676–2377,
1747, 1709 and 1651; δH(400 MHz, CDCl3) 7.11 (1H, br s,
᎐CH᎐), 5.16–5.05 (2H, m, 2 × ᎐CH᎐), 4.76 (2H, br s, CH O),
᎐
᎐
2
2.33–2.28 (6H, m), 2.06–1.99 (6H, m), 1.75–1.53 (2H, m), 1.60
(3H, s, Me) and 1.59 (3H, s, Me); δC(67.8 MHz, CDCl3) 179.0
(s), 174.8 (s), 144.5 (d), 136.4 (s), 134.1 (s), 133.9 (s), 125.1 (d),
122.8 (d), 70.1 (t), 39.5 (t), 38.7 (t), 33.2 (t), 26.3 (t), 25.6 (t),
25.4 (t), 22.6 (t), 16.0 (q) and 15.7 (q).
νmax(film)/cmϪ1 1755; δ (250 MHz, CDCl ) 7.11 (1H, m, ᎐CH᎐),
᎐
H
3
5.12–5.08 (2H, m, 2 × ᎐CH᎐), 4.76–4.74 (2H, m, CH O), 4.55
᎐
2
(1H, br s, CH2CHO2), 3.89–3.82 (1H, m), 3.77–3.68 (1H, m),
3.53–3.46 (1H, m), 3.43–3.31 (1H, m), 2.30–2.25 (4H, m), 2.04–
1.95 (6H, m), 1.89–1.40 (10H, m), 1.59 (3H, s, Me) and 1.58
(3H, s, Me); δC(67.8 MHz, CDCl3) 174.4 (s), 144.7 (d), 137.0 (s),
135.3 (s), 134.2 (s), 124.5 (d), 122.9 (d), 99.2 (d), 70.4 (t), 67.8
(t), 62.7 (t), 39.9 (t), 39.7 (t), 31.1 (t), 29.6 (t), 26.8 (t), 26.0 (t),
Se-Phenyl (E,E)-5,9-dimethyl-12-(2-oxo-5H-furan-3-yl)dodeca-
5,9-dieneselenoate 11
Tributylphosphine (164 µl, 133 mg, 0.653 mmol) was added
dropwise over 5 min to a stirred solution of the acid 19b (100
866
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
mg, 0.326 mmol) in dichloromethane (6.0 cm3) at Ϫ30 ЊC. After
5 min N-phenylselenophthalimide (197 mg, 0.653 mmol) was
added in one portion, and the mixture was then stirred at
Ϫ30 ЊC for 3 h. The mixture was diluted with dichloromethane
(20 cm3) and then washed with water (20 cm3) and brine (20
cm3). The separated aqueous layers were extracted with dichloro-
methane (20 cm3), and the combined organic extracts dried
(MgSO4) and then evaporated in vacuo. Chromatography of the
residue on silica gel using ethyl acetate–light petroleum (bp 40–
60 ЊC) (1:4) as eluent gave the selenyl ester (116 mg, 80%) as a
colourless oil; νmax(film)/cmϪ1 1754 and 1722; δH(250 MHz,
CDCl3) 7.53–7.49 (2H, m, 2 × aryl-H), 7.40–7.38 (3H, m, 3 ×
aryl-H), 7.10 (1H, br s, ᎐CH᎐), 5.15–5.07 (2H, m, 2 × ᎐CH᎐),
4.75 (2H, br s, CH2O), 2.67 (2H, t, J 7.3 Hz), 2.32–2.26 (4H, m),
2.06–1.98 (6H, m), 1.85–1.67 (2H, m) and 1.58 (6H, s, 2 × Me);
δC(67.8 MHz, CDCl3) 201.0 (s), 174.5 (s), 144.3 (d), 136.1 (s),
135.7 (d), 133.9 (s), 133.6 (s), 129.2 (d), 128.8 (d), 125.5 (d),
125.4 (s), 122.8 (d), 70.1 (t), 46.8 (t), 39.5 (t), 38.5 (t), 26.5 (t),
25.7 (t), 25.4 (t), 23.4 (t), 16.0 (q) and 15.7 (q); m/z (EI) 289.1811
(Mϩ Ϫ PhSe, C18H25O3 requires 289.1804).
reflections measured to 2θmax = 50Њ, giving 1830 with F у 4σ(F )
and 2679 which were retained in all calculations. Slight crystal
decay (4%) was observed and corrected for during data process-
ing; no corrections were applied for absorption.
Structure solution and refinement. Automatic direct
methods20 (all non-H atoms). Full-matrix least squares refine-
ment21 with all non-H atoms anisotropic; hydrogen atoms were
included at geometrically calculated positions and refined freely
with Uiso(H) = xUeq(C) [x = 1.5 for methyl hydrogens and 1.2
for others]. The weighting scheme wϪ1 = [σ2(Fc) ϩ (0.039P)2 ϩ
2
0.35P], P = 1/3[MAX(Fo ,0) ϩ 2Fc2], gave satisfactory agree-
ment analyses. Final R1 [F у 4σ(F )] = 0.0426, wR2 [all data] =
0.1039, S[F2] = 1.05 for 269 refined parameters. An extinction
correction21 refined to 0.0051(9) and the final ∆F synthesis
showed no peaks above 0.14 e ÅϪ3. Fig. 1 was produced
using SHELXTL/PC.22
Full crystallographic details, excluding structure factor
tables, have been deposited at the Cambridge Crystallo-
graphic Data Centre (CCDC). For details of the
deposition scheme, see ‘Instructions for Authors’, J. Chem.
Soc., Perkin Trans. 1, available via the RSC Web pages
(http://chemistry.rsc.org/rsc/p1pifa.htm). Any request to the
CCDC for this material should quote the full literature citation
and the reference number 207/183.
᎐
᎐
(5â,13á)- and (5á,13á)-8-Methyl-18-nor-16-oxaandrostan-4,17-
dione 20
A solution of the phenylselenyl ester 11 (111 mg, 0.249 mmol)
and AIBN (15 mg) in dry degassed benzene (25 cm3) was
warmed to reflux under argon and then treated dropwise over
8 h with a solution of tributyltin hydride (101 µl, 109 mg,
0.3742 mmol) and AIBN (15 mg) in benzene (6 cm3). The mix-
ture was heated under reflux for a further 12 h, then cooled and
the solvent removed in vacuo. Chromatography of the residue
on silica gel using ethyl acetate–light petroleum (bp 40–60 ЊC)
(3:7) as eluent gave (i) the cis,anti,trans,anti,cis-diastereoisomer
of the tetracycle (eluted first) (9 mg, 12%) as a white amorphous
solid; νmax(CH2Cl2) 1764 and 1708; δH(360 MHz, CDCl3) 4.20
(1H, d, J 9.9 Hz, H-15), 4.10 (1H, dd, J 9.9, 5.3 Hz, H-15), 2.54
(1H, dd, J 7.9, 7.9 Hz, H-13), 2.39–2.22 (4H, m), 2.18 (1H, br s),
2.09 (1H, dd, J 7.9, 5.3 Hz, H-14), 2.06–2.03 (1H, m), 1.96–1.25
(8H, m), 1.11 (3H, s, Me), 1.08–1.04 (1H, m), 0.91 (3H, s, Me)
and 0.88–0.80 (1H, m); δC(90.6 MHz, CDCl3) 212.7 (s), 178.8
(s), 67.6 (t), 55.5 (d), 50.1 (d), 45.1 (d), 41.4 (t), 40.1 (s), 38.6 (t),
37.3 (d), 35.4 (s), 35.4 (t), 25.5 (q), 22.1 (t), 20.1 (t), 17.6 (t), 16.5
(t) and 15.3 (q); m/z (EI) 290.1884 (Mϩ, C18H26O3 requires
290.1882); and (ii) the trans,anti,trans,anti,cis-diastereoisomer
of the tetracycle (eluted second) (38 mg, 53%) as white needles,
mp 178–180 ЊC (from ethyl acetate–light petroleum); νmax(CH2-
Cl2)/cmϪ1 1764 and 1708; δH(500 MHz, CDCl3) 4.22 (1H, d,
J 9.9 Hz, H-15), 4.12 (1H, dd, J 9.9, 5.4 Hz, H-15), 2.58 (1H,
dd, J 7.9, 7.9 Hz, H-13), 2.35 (1H, m), 2.29 (1H, dd, J 4.6, 4.6
Hz), 2.17 (1H, dd, J 11.6, 3.5 Hz), 2.12 (1H, dd, J 7.9, 5.4 Hz,
H-14), 2.00–1.92 (2H, m), 1.91–1.86 (1H, m), 1.83 (1H, app. dt,
J 13.1, 13.2 Hz), 1.73–1.50 (4H, m), 1.39–1.28 (2H, m), 1.04
(1H, dd, J 12.2, 1.9 Hz), 0.98–0.88 (2H, m), 0.88 (3H, s, Me)
and 0.72 (3H, s, Me); δC(125 MHz, CDCl3) 212.6 (s), 178.7 (s),
67.4 (t), 59.6 (d), 53.8 (d), 50.3 (d), 42.6 (s), 40.5 (t), 39.0 (t),
38.4 (t), 37.2 (d), 35.4 (s), 22.1 (t), 21.9 (t), 18.1 (t), 16.6 (t), 15.1
(q) and 14.2 (q); m/z (EI) 290.1885 (Mϩ, C18H26O3 requires
290.1882).
(5á,13á)-8-Methyl-4-methylene-18-nor-16-oxaandrostan-17-one
22
A solution of titanium tetrachloride (10 cm3, 10.0 mmol, 1.0 
in CH2Cl2) was added dropwise over 10 min to a vigorously
stirred suspension of activated zinc dust (2.87 g, 44.0 mmol)
and dibromomethane (1.01 cm3, 2.43 g, 14.0 mmol) in THF (25
cm3) at Ϫ40 ЊC. The mixture was warmed to 0 ЊC, and then
stirred in a cold room at 0 ЊC for 18 h. A portion (0.5 cm3) of
this Lombardo reagent was added dropwise over 5 min to a
solution of the ketone 20 (10 mg, 0.0344 mmol) in dichloro-
methane (1 cm3) at 0 ЊC, and the reaction was then stirred
at 0 ЊC for 30 min. The mixture was poured into saturated
aqueous sodium hydrogen carbonate (15 cm3) and then
extracted with diethyl ether (20 cm3). The separated organic
phase was washed with water (20 cm3), and both separated
aqueous layers were then extracted with diethyl ether (20 cm3).
The combined organic extracts were dried (MgSO4) and then
evaporated in vacuo. Chromatography of the residue on silica
gel using ethyl acetate–light petroleum (bp 40–60 ЊC) (3:17) as
eluent gave the alkene (7.8 mg, 79%) as white needles, mp 130–
135 ЊC (from diethyl ether–light petroleum); νmax(CH2Cl2)/cmϪ1
1771 and 1645; δ (500 MHz, CDCl ) 4.72 (1H, s, ᎐CHH), 4.47
᎐
H
3
(1H, s, ᎐CHH), 4.23 (1H, d, J 9.8 Hz, H-15), 4.12 (1H, d, J 9.8,
᎐
5.4 Hz, H-15), 2.57 (1H, dd, J 8.0, 8.0 Hz, H-13), 2.34 (1H, dd,
J 14.0, 4.4 Hz), 2.28 (1H, dd, J 13.0, 4.4 Hz), 2.13 (1H, dd, J 8.0,
5.4 Hz, H-14), 1.98 (1H, ddd, J 13.0, 13.0, 5.9 Hz), 1.86–1.79
(2H, m), 1.72–1.41 (5H, m), 1.39–1.17 (2H, m), 1.08 (1H, ddd,
J 12.9, 12.9, 4.0 Hz), 1.01 (1H, ddd, J 13.0, 13.0, 4.8 Hz), 0.97–
0.83 (2H, m), 0.89 (3H, s, Me) and 0.65 (3H, s, Me); δC(125
MHz, CDCl3) 179.0 (s), 150.5 (s), 105.4 (t), 67.5 (t), 54.0 (d),
52.5 (d), 50.4 (d), 40.3 (t), 39.7 (t), 39.1 (s), 37.4 (d), 36.3 (t),
35.7 (s), 23.0 (t), 22.4 (t), 20.4 (t), 18.0 (t), 15.2 (q) and 13.8 (q);
m/z (EI) 288.2099 (Mϩ, C19H28O2 requires 288.2089).
X-Ray crystal structure determination of 20
A colourless block was mounted on a glass fibre and transferred
to the diffractometer.
(5á,13á)-8Ј-Methylspiro[cyclopropane-1,4Ј-[18]nor[16]oxa-
androstan[17]one] 23
Crystal data. C18H26O3, M = 290.39, monoclinic, a =
A solution of diiodomethane (6.5 µl, 21.7 mg, 0.081 mmol) in
diethyl ether (0.2 cm3) was added dropwise over 2 h to a reflux-
ing mixture of zinc–copper couple (9 mg, 0.135 mmol) and the
alkene 22 (3.9 mg, 0.0135 mmol) in diethyl ether (0.5 cm3). The
mixture was heated under reflux for a further 60 h, then cooled
and diluted with diethyl ether (20 cm3) and water (20 cm3). The
separated aqueous layer was extracted with diethyl ether (20
cm3) and the combined organic extracts were dried (MgSO4)
and evaporated in vacuo. Chromatography of the residue on
7.561(2), b = 17.779(2), c = 11.949(2) Å, β = 106.99(2)Њ, V =
1536.1(5) Å3 [from 2θ values of 48 reflections measured at
ω
(28 р 2θ р 34Њ, λ = 0.710 73 Å, T = 298 K)], space group P21/c
(No. 14), Z = 4, Dx = 1.256 g cmϪ3, colourless block 0.42 ×
0.35 × 0.27 mm, µ(Mo-Kα) = 0.084 mmϪ1.
Data collection and processing. Stoe Stadi-4 four-circle dif-
fractometer, ω/θ scans with ω scan width (0.90 ϩ 0.35 tan θ)Њ,
graphite-monochromated Mo-Kα X-radiation; 2689 unique
J. Chem. Soc., Perkin Trans. 1, 1998
867

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3 T. W. Hambley, A. Poiner and W. C. Taylor, Aust. J. Chem., 1990, 43,
silica gel using ethyl acetate–light petroleum (bp 40–60 ЊC)
(3:17) as eluent gave the cyclopropane (4.1 mg, 95%) as white
needles, mp 144–148 ЊC (from diethyl ether–light petroleum);
νmax(CH2Cl2)/cmϪ1 2929, 2850 and 1770; δH(500 MHz, CDCl3)
4.20 (1H, d, J 9.8 Hz, H-15), 4.11 (1H, dd, J 9.8, 5.4 Hz, H-15),
2.55 (1H, dd, J 8.0, 7.8 Hz, H-13), 2.32 (1H, dd, J 14.0, 5.2 Hz),
2.10 (1H, dd, J 7.8, 5.4 Hz, H-14), 1.84 (1H, br d, J 12.5 Hz),
1.78–1.74 (2H, m), 1.72–1.55 (4H, m), 1.48–1.41 (2H, m), 1.31
(1H, ddd, J 12.8, 12.8, 4.9 Hz), 1.09–0.81 (4H, m), 0.85 (6H, s,
2 × Me), 0.79 (1H, dd, J 12.4, 2.0 Hz), 0.46–0.41 (2H, m,
2 × cyclopropyl), 0.25–0.22 (H, m, cyclopropyl) and Ϫ0.16 to
Ϫ0.19 (1H, m, cyclopropyl); δC(125 MHz, CDCl3) 179.2 (s),
67.6 (t), 54.5 (d), 50.6 (d), 48.9 (d), 40.8 (t), 40.1 (t), 38.8 (t), 38.4
(s), 37.5 (d), 35.6 (s), 22.5 (t), 20.7 (t), 19.0 (s), 17.6 (2 × t), 15.5
(q), 14.7 (q), 9.3 (t) and 6.1 (t); m/z (EI) 302.2242 (Mϩ, C20H30O2
requires 302.2246).
1861.
4 A. G. Gonzalez, D. M. Estrada, J. D. Martin, V. S. Martin, C. Perez
and R. Perez, Tetrahedron, 1984, 40, 4109.
5 S. Kohmoto, O. J. McConnell, A. Wright and S. Cross, Chem. Lett.,
1987, 168; R. Kazauskas, P. T. Murphy, R. J. Wells, K. Noack,
W. E. Oberhansli and P. Schonoholzer, Aust. J. Chem., 1979, 32, 867.
6 T. Nakano and M. I. Hernández, Tetrahedron Lett., 1982, 1423;
D. S. de Miranda, G. Brendolan, P. M. Imamura, M. González-
Sierra, A. J. Marsaioli and E. A. Rúveda, J. Org. Chem., 1981,
46, 4851; P. M. Imamura, M. González-Sierra and E. A. Rúveda,
J. Chem. Soc., Chem. Commun., 1981, 734; T. Nakano, M. I.
Hernández, M. Gomez and J. D. Medina, J. Chem. Res. Synop.,
1989, 54; M. G. Sierra, M. P. Mischne and E. A. Rúveda, Synth.
Commun., 1985, 15, 27; T. Sakamoto and K. Kanematsu,
Tetrahedron, 1995, 51, 5771.
7 For studies of oxidative radical cyclisations of polyenes and
applications to the synthesis of ( )-isospongiadiol see: P. A. Zoretic,
M. Wang, Y. Zhang and Z. Shen, J. Org. Chem., 1996, 61, 1806
and references cited therein.
(5á,13á)-4,4,8-Trimethyl-18-nor-16-oxaandrostan-17-one
(spongian-16-one) 1
8 L. Chen, G. B. Gill, G. Pattenden and H. Simonian, J. Chem. Soc.,
Perkin Trans. 1, 1996, 31; A. Batsanov, L. Chen, G. B. Gill and
G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1996, 45 and references
cited therein.
Platinum() oxide (1.5 mg, 0.0066 mmol, 50 mol%) was added
to a solution of the cyclopropane 23 (4 mg, 0.0132 mmol) in
distilled glacial acetic acid (0.2 cm3), and the mixture was then
stirred under an atmosphere of hydrogen for 40 h. The mixture
was diluted with diethyl ether (20 cm3) and then washed with
saturated aqueous sodium hydrogen carbonate (2 × 15 cm3).
The combined organic extracts were dried (MgSO4) and then
evaporated in vacuo. Chromatography of the residue on silica
gel using ethyl acetate–light petroleum (bp 40–60 ЊC) (3:17) as
eluent gave ( )-spongian-16-one (3.2 mg, 80%) as white needles,
mp 137–139 ЊC (from diethyl ether–light petroleum) (Found: C,
78.2; H, 10.6. C20H32O2 requires C, 78.1; H, 10.7%); νmax(CH2-
Cl2)/cmϪ1 2977, 2928, 2869, 1768, 1444, 1386 and 1111; δH(500
MHz, CDCl3) 4.22 (1H, d, J 9.8 Hz, H-15), 4.11 (1H, dd, J 9.8,
5.4 Hz, H-15), 2.54 (1H, dd, J 7.8, 7.8 Hz, H-13), 2.31 (1H, dd,
J 14.1, 5.0 Hz), 2.09 (1H, dd, J 7.8, 5.4 Hz, H-14), 1.84 (1H,
ddd, J 12.7, 3.2, 3.2 Hz), 1.74 (1H, br d, J 12.7 Hz), 1.69–1.50
(4H, m), 1.44–1.24 (5H, m), 1.14 (1H, ddd, J 13.2, 13.2, 4.1 Hz),
1.04 (1H, ddd, J 12.9, 12.9, 3.8 Hz), 0.87 (3H, s, Me), 0.86 (3H,
s, Me), 0.83 (3H, s, Me), 0.82 (3H, s, Me), 0.89–0.79 (1H, m)
and 0.76 (1H, dd, J 12.0, 2.4 Hz); δC(125 MHz, CDCl3) 179.0
(s), 67.6 (t), 56.7 (d), 56.4 (d), 50.6 (d), 42.2 (t), 42.0 (t), 40.0 (t),
37.4 (d), 37.4 (s), 35.7 (s), 33.4 (q), 33.4 (s), 22.4 (t), 21.5 (q),
18.5 (t), 17.9 (t), 17.3 (t), 16.3 (q) and 15.5 (q); m/z (EI) 304.2345
(Mϩ, C20H32O2 requires 304.2402).
9 P. Double and G. Pattenden, unpublished work.
10 G. Pattenden and L. Roberts, Tetrahedron Lett., 1996, 37, 4191.
11 S. Hatakeyama, H. Numata, K. Osanai and S. Takano, J. Chem.
Soc., Chem. Commun., 1989, 1893; cf. G. Cahiez, A. Alexakis and
J. F. Normant, Tetrahedron Lett., 1978, 3013; S. A. Godleski,
D. J. Heacock, J. D. Meinhart and S. Van Wallendael, J. Org. Chem.,
1983, 48, 2101; S. A. Stanton, S. W. Felman, C. S. Parkhurst and
S. A. Godleski, J. Am. Chem. Soc., 1983, 105, 19.
12 W. S. Johnson, R. A. Buchanan, W. R. Bartlett, F. S. Tham and
R. K. Knullnig, J. Am. Chem. Soc., 1993, 115, 504.
13 M. Julia, S. Julia and R. Guegan, Bull. Soc. Chim. Fr., 1960, 1072.
14 K. Iwai, H. Kosugi, H. Uda and M. Kawai, Bull. Chem. Soc. Jpn.,
1977, 50, 242.
15 B. M. Trost, M. K.-T. Mao, J. M. Balkovec and P. Buhlmayer,
J. Am. Chem. Soc., 1986, 108, 4965.
16 K. C. Nicolaou, N. A. Petasis and D. A. Claremon, Tetrahedron,
1985, 41, 4835.
17 L. Lombardo, Org. Synth., 1987, 81.
18 P. A. Wender and S. L. Eck, Tetrahedron Lett., 1982, 1871; B. M.
Trost and H. Hiemstra, J. Am. Chem. Soc., 1982, 104, 886;
W. Oppolzer and T. Godel, J. Am. Chem. Soc., 1978, 100, 2583.
19 The data reported by Cambie (ref. 2) for natural spongian-16-one
isolated from D. cavernosa [mp 155–159 ЊC; [α]D ϩ53 (c 0.0011,
CHCl3)] differ somewhat to the data [mp 200 ЊC, [α]D Ϫ6.7 (c 1.0),
certain shift data in the 1H NMR spectrum] reported for spongian-
16-one from C. violacea (ref. 3). A stereoisomer of 1, with the
opposite stereochemistry at C13 (i.e. trans ring fused lactone) has
been characterised amongst the products of hydrogenation of
natural 3, a metabolite from Spongia officinalis (ref. 4); this
compound is non-crystalline and shows [α]D ϩ14.2 (c, 0.9
CHCHl3).
Acknowledgements
We thank Professor R. C. Cambie (The University of Auck-
20 G. M. Sheldrick, SHELXS-86, Acta Crystallogr., Sect. A, 1990, 46,
1
land, New Zealand) for supplying copies of the H and 13C
467.
21 G. M. Sheldrick, SHELXL-93, University of Göttingen, Germany,
1993.
22 G. M. Sheldrick, SHELXTL/PC, version 5.03, Siemens Analytical
Instruments Inc., Madison, WI, 1995.
NMR spectra of natural spongian-16-one from D. cavernosa.
We also thank Glaxo Wellcome (formally Glaxo Group
Research) for a Research Fellowship (to L. R.) and Dr D.
Tapolczay for his interest in this study.
References
1 G. Cimino, R. Morrone and G. Sodano, Tetrahedron Lett., 1982, 23,
Paper 7/08042E
Received 7th November 1997
Accepted 17th December 1997
4139.
2 M. R. Kernan, R. C. Cambie and P. R. Bergquist, J. Nat. Prod., 1990,
53, 724.
868
J. Chem. Soc., Perkin Trans. 1, 1998