Studies on the stereostructure of eudesmanolides from Umbelliferae: Total synthesis of (+)-decipienin A

Article abstract of DOI:10.1016/S0040-4020(00)00240-4

The first total synthesis of (+)-decipienin A has been achieved in 4% overall yield in seven steps from (+)-dihydrocarvone, thus confirming the stereostructure proposed by Holub et al. (Holub, M.; Budesinsky, M. Phytochemistry 1986, 25, 2015-2026) for thi

Full text of DOI:10.1016/S0040-4020(00)00240-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3409±3414
Studies on the Stereostructure of Eudesmanolides from
Umbelliferae: Total Synthesis of (1)-Decipienin A
a,
Francisco A. Macõas, Jose Marõa Aguilar, Jose Marõa G. Molinillo,
a
a
*
Â
Â
Â
Â
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Francisco Rodrõguez-Luõs, Isidro G. Collado, Guillermo M. Massanet and Frank R. Fronczek
a
a
a,
b
*
Â
Â
a
   Â
Departamento de Quõmica Organica, Facultad de Ciencias, Universidad de Cadiz, C/Republica Saharaui s/n, Apdo. 40,
Â
11510-Puerto Real, Cadiz, Spain
bDepartment of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Received 25 October 1999; revised 29 February 2000; accepted 16 March 2000
AbstractÐThe ®rst total synthesis of (1)-decipienin A has been achieved in 4% overall yield in seven steps from (1)-dihydrocarvone, thus
con®rming the stereostructure proposed by Holub et al. (Holub, M.; Budesinsky, M. Phytochemistry 1986, 25, 2015±2026) for this lactone
and the original assignments should be corrected as indicated in by formula (a) (6aH,7aH,10amethyl-eudesman-6,12-olide). Two different
strategies were used, the ®rst one an attempt to build the a-hydroxy-g-lactone moiety through functionalization of the C-6 position and the
second involved the introduction of the C-11 hydroxyl group at the ®nal steps of the synthetic scheme. q 2000 Elsevier Science Ltd. All
rights reserved.
Introduction
man-6,12-olide) instead of formula (b) (6bH,7aH,10b-
methyl-eudesman-6,12-olide)4 (Fig. 1).
Sesquiterpene lactones constitute the most characteristic
secondary metabolites isolated from Compositae.1 This
group of natural products shows a wide range of structural
types and very interesting biological activities.2,3
Previously we reported the synthesis of decipienin A (1)
having the stereostructure b.5 The observed differences
between spectroscopic and physical data of this compound
and those reported for the natural product led us to conclude
that the original proposed stereostructure6 is not correct. In
order to con®rm that a stereostructure type a should be
assigned, here we report the preparation of decipienin A
(1a) from (1)-dihydrocarvone (2).
Umbelliferae represent the second major source of natural
sesquiterpene lactones. Holub showed that the majority of
sesquiterpene lactones obtained from Umbelliferae have
a
different stereostructure than those isolated from
Compositae. Based on spectroscopic grounds, he proposed
that decipienin A and other eudesmanolides isolated from
Melanoselinum decipiens (Schrader±Wendl.) Hoffm.
(Umbelliferae, tribe Laserpietieae) have basic structure
represented by formula (a) (6aH,7aH,10amethyl-eudes-
Results and Discussion
The key intermediate in the synthesis was (2)-10-epi-a-
Figure 1.
Keywords: terpenoids; enolates; annulation; stereocontrol.
* Corresponding authors.: Tel.: 134-956-016370; fax: 134-956-016288; e-mail: famacias@uca.es
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00240-4

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F. A. Macõas et al. / Tetrahedron 56 (2000) 3409±3414
3410
Scheme 1.
cyperon (4), which is readily available from Robinson
annulation of (1)-dihydrocarvone (2) with ethylvinyl-
ketone.7 The product of this reaction is known to be ketol
3, which can be dehydrated by treatment with KOH in dry
MeOH to give 4 in high yield (Scheme 1).
Cyanohydrin 9 was obtained in 60% yield from methyl-
ketone 4. Hydrolysis of 9 gave the corresponding amide
11 in very low yield (below 5%), instead of the desired
a-hydroxyacid 10.
The second option consisted of different approach (Scheme
4) which involved the introduction of the C-11 hydroxyl
group in the ®nal steps of the sequence.
The ®rst attempt to build the a-hydroxy-g-lactone moiety
through functionalization of the C-6 position in hydroxy
acid 7 was planned as shown in Scheme 2.
Hydroboration of 4 with B2H6 in THF under N2 atmosphere
gave the primary alcohol 12 in 76% yield which was
treated with Jones reagent to afford a complex mixture
from which the corresponding acid could not be
isolated. However when oxidation with Jones reagent
was followed by treatment with phenyltrimethylammo-
nium bromide in dioxane, the dibromoacid derivative 13
was `trapped' as the corresponding lactone 14 in 60%
yield. In this case, dibromide intermediate 13 presents
the correct con®guration at C-6 to allow the obtention
of the cis-lactone by nucleophilic displacement of the
bromine atom.
Oxidation of 4 with m-chloroperbenzoic acid afforded
epoxide 5 in 90% yield, which was converted to diol 6 by
opening of the oxirane ring with different acids [HClO4(3.0,
0.5, 0.25, 0.125 M)/THF, p-TsOH, H2SO4/(CH3)2CO] in a
ca 10±20% yield. Attempted oxidation of 6 with chromium
trioxide-pyridine, or pyridine chlorochromate, led to a
mixture of products in a 15% overall yield. The major
product isolated from these mixtures was the methyl ketone
8, derived from the oxidative cleavage of the diol. There-
fore, we explored the sequence outlined in Scheme 3, using
this ketone 8 as starting material (Scheme 3).
Scheme 2.
Scheme 3.

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F. A. Macõas et al. / Tetrahedron 56 (2000) 3409±3414
3411
Scheme 4.
The absolute con®guration, established by the X-ray
analysis8 of 14 (Fig. 2), con®rmed that con®guration at
the chiral centres C-6, C-7, and C-10 ®t the stereochemical
requirements proposed by Holub for the eudesmanolides
isolated from plants of the Umbelliferae (6aH, 7aH, 14b-
methyl). Elimination of the bromine atom at C-2 was
accomplished by treatment with Li2CO3 in DMF to provide
dienone 15 in 75% yield.
Hydroxylation of 15 using this procedure gave 16 in 57%
yield. Esteri®cation of 16 with angelic chloride in pyridine
proceeded with isomerization of the double bond to give the
tiglate derivative. When the reaction was carried out using
the mixed anhydride obtained from angelic acid and 2,4,6-
trichlorobenzoyl chloride, (1)-decipienin A (1) was
obtained in 32% yield. The synthetic decipienin A was iden-
tical with the natural product isolated from Melanoselinum
decipiens.6
The introduction of the hydroxyl group at C-11 in lactone 15
presented several problems as we have described previously
for related compounds.9 Treatment with Vedejs' reagent10
resulted in the formation of complex mixtures, and the use
of a ¯ow of molecular oxygen in THF and LDA effected
lactone decarbonylation to give the corresponding methyl-
ketone instead of the hydroxylation product.
In conclusion, the total synthesis of (1)-decipienin A (1)
has been achieved for the ®rst time in 6% overall yield in
®ve steps from cyperon 4, thus con®rming the stereo-
structure proposed by Holub et al. for this lactone and that
the original assignments should be corrected as indicated in
Fig. 1a.
In the course of our studies on chemical transformations of
sesquiterpene lactones we have reported a new method for
hydroxylation at the C-11 position,11 where the enolate is
generated by deprotonation with potassium hexamethyl-
disilazide (KHMDS), trapped by using a ¯ow of molecular
oxygen in THF, and reduced `in situ' with triethyl
phosphite, that avoid the decarboxylation problems.4,8
Experimental
Materials and general procedures
Infrared spectra were recorded on a Perkin±Elmer 257 spec-
trometer in ®lm. 1H NMR and 13C NMR spectra were made
Figure 2. X-Ray structure of 14.

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F. A. Macõas et al. / Tetrahedron 56 (2000) 3409±3414
3412
on Varian Gemini-200 and Bruker AM-400 spectrometers,
using CDCl3 as internal standard. Mass spectra were
recorded on a VG 12±250 spectrometer using 70 eV.
Chromatographic separations were made on silica gel
(Merck), employing hexane, ethyl acetate mixtures as
eluent.
mixture of i-propanol and water (8:2) and MCPBA (200 mg,
1.16 mmol) was added. After 20 h the reaction mixture was
neutralized with a solution of aq. NaOH (5%), and extracted
with ethyl ether (5£5 mL). The organic layer was chroma-
tographed (Hexane:Et2O, 7:3) to yield 73 mg (0.31 mmol,
85%) of 5 as colourless oil. Different methods for opening
the epoxide were tested, including HClO4 (0.125, 0.25, 0.5,
3.0 M) in THF, p-toluensulfonic acid, H2SO4/acetone,
obtaining low yields of 6 in all cases (ca 15% yield) as
colourless oil. Subsequent oxidation of this compound
with KMnO4 afforded methylketone 8 (53%) as yellow
oil, instead of the corresponding a-hydroxyacid 7.
8a-Hydroxy-4aa-methyl-7b-(propen-2-yl)-perhydro-
naphtalen-2-one (3)
A solution of dry ethanol (1.2 mL) and KOH (366 mg,
6.5 mmol) was added to a solution of dihydrocarvone (5 g,
32.9 mmol) in ethyl ether (10 mL) at 08C under N2
atmosphere. After the mixture has been stirred for 10 min
a solution of ethylvinylketone (1.25 g, 14.9 mmol) in ethyl
ether (7.2 mL) was introduced dropwise during one hour.
The mixture was stirred for one hour, then it reached 308C
and allowed to stand for 1.5 h. The solution was neutralized
with aq. HCl (5%) turning from orange to yellowish and
then extracted with ethyl ether (5£10 mL). The ether layer
was washed with brine and dried with Na2SO4. Then, the
solvent was removed under reduced pressure. The residue
was chromatographed (Hexane:AcOEt 4:1) to give 3
(2.46 g, 10.43 mmol, 70%) as colourless oil.
5: IR (KBr)neat max: 1656 (a,b-unsaturated ketone) cm21
n ;
MS, m/z (relative intensity), C15H22O2: 234 [M]1 (20), 219
[M2CH3]1 (13), 203 [M2CH2O]1 (66), 176 [M2C3OH6]
(78); dH (200 MHz, CDCl3): 2.85 (1H, ddd, Jˆ15, 2, 2 Hz,
H-2) 2.75±2.68 (3H, m, H-6, H-60, H-7), 2.60 (1H, d,
Jˆ6 Hz, H-12), 2.48 (1H, d, Jˆ6 Hz, H-120), 2.33 (1H,
ddd, Jˆ15, 6.5, 1.5 Hz, H-20), 1.81 (3H, s, H-15), 1.69±
1.24 (6H, m, H-1, H-8, H-9), 1.36 (3H, s, H-13), 1.21
(3H, s, H-14). HREIMS: M1, found 234.1620. C15H22O2
requires 234.1620.
6: IR (KBr)neat
nmax: 3480 (hydroxyl group), 1650 (a,b-
unsaturated ketone) cm21; MS, m/z (relative intensity)
C15H24O3: 252 [M]1 (4), 234 [M2H2O]1 (17), 221
[M2CH3O] (21); dH (200 MHz, CDCl3): 3.81 (1H, d,
Jˆ9.5 Hz, H-12), 3.62 (1H, d, Jˆ9.5 Hz, H-120), 2.87
(1H, ddd, Jˆ15, 2, 2 Hz, H-2), 2.72-2.48 (3H, m, H-6,
H-60 and H-7), 2.39 (1H, ddd, Jˆ15, 6, 2 Hz, H-20), 1.99
(3H, brs, H-15), 1.70±1.28 (6H, m, H-1, H-8, H-9), 1.35
(3H, s, H-13), 1.18 (3H, s, H-14). HREIMS: M1, found
252.1730. C15H24O3 requires 252.1725.
3: IR (KBr)neat nmax: 3500 (hydroxyl group), 1694 (ketone),
1638 (C±C double bond) cm21; MS, m/z (relative intensity),
C15H24O2: 236 [M]1 (13), 218 [M2H2O]1 (6), 109
[C8H13]1 (100); dH (200 MHz, CDCl3): 4.68±4.65 (1H, m,
H-12), 4.64±4.62 (1H, m, H-120), 2.83 (1H, dq, Jˆ7, 1 Hz,
H-4), 2.55 (1H, dddd, Jˆ14, 14, 7, 1 Hz, H-2), 2.30 (1H,
ddd, Jˆ14, 5, 2 Hz, H-20), 2.23±2.20 (1H, m, H-7), 1.85±
1.70 (2H, m, H-6 and H-60), 1.65 (3H, dd, Jˆ1, 1 Hz, H-13),
1.58±1.20 (6H, m, H-1, H-8, H-9), 1.21 (3H, s, H-14), 1.01
(3H, s, H-15).
8: IR (KBr)neat
nmax: 1714 (ketone), 1645 (a,b-unsaturated
ketone), 1604 (C±C-double bond) cm21; MS, m/z (relative
intensity), C14H20O2: 220 [M]1 (8), 205 [M2CH3]1 (4), 178
[M2C2HO]1 (23), 43 [CH3CO]1 (100); dH (200 MHz,
CDCl3): 2.74 (1H, ddd, Jˆ16, 3, 2 Hz, H-2), 2.63±2.34
(3H, m, H-6, H-60, H-7), 2.21 (1H, brdd, Jˆ16, 6 Hz,
H-20), 2.16 (3H, s, H-13), 1.79 (3H, brs, H-15), 1.67±1.27
(6H, m, H-1, H-8, H-9), 1.23 (3H, s, H-14). HREIMS: M1,
found 220.1469. C14H20O2 requires 220.1463.
(2)-10-epi-a-Cyperon (4)
Alcohol 3 (1.3 g, 5.5 mmol) was dissolved in 20 mL of a
solution of KOH (10%) in dry MeOH. The mixture was
heated at re¯ux under N2 atmosphere for 8 h, after which
it was cooled, diluted with water (25 mL), and neutralized
with aq. HCl (5%). The mixture was extracted with ethyl
ether (5£15 mL), and the organic layer was washed with
brine and dried with Na2SO4. Then, the solvent was
removed under reduced pressure. The residue was chroma-
2-[1,2,3,4,4a,5-Hexahydro-4aa,8-dimethyl-7(6H)-oxo-
napht-2-yl]-2-hydroxy-propanenitrile (9)
tographed (Hexane:AcOEt 49:1) to give
5.05 mmol, 92%) as colourless oil.
4 (1.1 g,
Ketone 8 (44 mg, 0.2 mmol) was dissolved in THF/H2O
(2.5 mL) and a few drops of HClO4 and KCN (20 mg,
0.31 mmol) were added. The reaction was monitorized by
TLC, and when it was complete was neutralized with a
solution of aq. HCl (5%), and extracted with ethyl ether
(5£5 mL). Chromatography (Hexane:AcOEt, 3:1) afforded
9 (30 mg, 0.12 mmol, 60%) as yellow oil.
4: [a]2D0ˆ2171.6 (c 0.1, CHCl3); IR (KBr)neat
nmax: 1654
(a,b-unsaturated ketone), 1603 (C±C double bond) cm21
;
MS, m/z (relative intensity), C15H22O: 218 [M]1 (58), 203
[M2CH3]1 (36); dH (200 MHz, CDCl3): 4.80 (1H, brs,
H-12), 4.62 (1H, brs, H-120), 2.89 (1H, ddd, Jˆ16, 2,
2 Hz, H-2), 2.36 (1H, ddd, Jˆ16, 6.5, 1.5 Hz, H-20), 2.7±
2.3 (3H, m, H-6, H-60 and H-7a), 1.81 (3H, s, H-15), 1.72
(3H, dd, Jˆ1, 1 Hz, H-13), 1.65±1.20 (6H, m, H-1, H-8,
H-9), 1.24 (3H, s, H-14). HREIMS: M1, found 218.1668.
C15H22O requires 218.1671.
Cyanohydrin 9 (10 mg, 0.04 mmol) was dissolved in THF
(5 mL) and 2.0 mL of aq. H2SO4 (5%) were added. After
12 h it was neutralized with a solution of aq. NaOH (5%),
and extracted with ethyl ether (5£5 mL). The organic layer
was chromatographed (Hexane: Et2O, 7:3) to give the corre-
sponding amide 11 in very low yield (below 5%) as colour-
less oil, instead of the desired a-hydroxyacid 10.
11,12-Epoxycyperon (5)
Alkene 4 (80 mg, 0.37 mmol) was dissolved in 5 mL of a

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F. A. Macõas et al. / Tetrahedron 56 (2000) 3409±3414
3413
9: IR (KBr)neat
n
max: 3400 (hydroxyl group), 2245 (nitrile),
chromatography an epimeric mixture of bromolactone 14
was obtained (659 mg, 2.02 mmol, 60%) as yellow crystals.
1640 (a,b-unsaturated ketone) cm21; MS, m/z (relative
intensity), C15H21NO2: 247 [M]1 (3), 221 [M2CN]1 (4),
229 [M2H2O]1 (24); dH (200 MHz, CDCl3): 2.65 (1H,
ddd, Jˆ16, 2, 1 Hz, H-2), 2.54±2.30 (3H, m, H-6, H-60,
H-7), 2.15 (1H, ddd, Jˆ16, 7, 1 Hz, H-20), 1.80 (3H, brs,
H-15), 1.71±1.28 (6H, m, H-1, H-8, H-9), 1.35 (3H, s,
H-13), 1.21 (3H, s, H-14). HREIMS: M1, found 247.1570.
C15H21NO2 requires 247.1572.
14: IR (KBr)neat
unsaturated) cm21
n
max: 1762 (g-lactone), 1650 (ketone a,b-
MS, m/z (relative intensity),
;
C15H19BrO3: 326 [M]1 (8), 328 [M12]1 (8), 247 [M2Br]1
(80), 233 [M2Br±CH3]1 (14), 219 [M2Br±CO]1 (40); dH
(400 MHz, CDCl3): 5.17 (1H, d, Jˆ5 Hz, H-6), 4.94 (1H, dd,
Jˆ9.5, 9.5 Hz, H-2), 2.88 (1H, dq, Jˆ7, 7 Hz, H-11), 2.59
(1H, dd, Jˆ14, 9.5 Hz, H-1), 2.38 (1H, dd, Jˆ14, 9.5 Hz,
H-10), 1.94 (3H, s, H-15), 1.62±1.38 (5H, m, H-7a, H-8a,
H-8b, H-9a, H-9b), 1.28 (3H, s, H-14), 1.24 (3H, d,
Jˆ7 Hz, H-13). HREIMS: M1, found 326.0522.
C15H19BrO3 requires 326.0518.
11: IR (KBr)neat
nmax: 3450 (hydroxyl group), 3330, 3150
(H±N, amide), 1650 (a,b-unsaturated ketone and amide)
cm21. MS, m/z (relative intensity), C15H23NO3: 265 [M]1
(10), 247 [M2H2O]1 (23); dH (200 MHz, CDCl3): 2.68
(1H, ddd, Jˆ15, 2, 1 Hz, H-2), 2.62±2.30 (3H, m, H-6, H-
60, H-7), 2.20 (1H, ddd, Jˆ15, 6, 2 Hz, H-20), 1.78 (3H, s,
H-15) 1.73±1.30 (6H, m, H-1, H-8, H-9), 1.34 (3H, s, H-13),
1.24 (3H, s, H-14). HREIMS: M1, found 265.1681.
C15H23NO3 requires 265.1678.
Isomer of a-santonin 15
To a suspension of dry LiBr (64 mg, 0.74 mmol) and
Li2CO3 (84 mg, 1.14 mmol) in dry DMF (20 mL) at
1208C under nitrogen atmosphere was added 14 (120 mg,
0.37 mmol). After the mixture was stirred for 75 min at
120±1258C, it was cooled and aq. acetic acid (5%) was
added. The reaction mixture was extracted with AcOEt
(5£20 mL), and the organic layer concentrated under
reduced pressure. Chromatography (Hexane:AcOEt, 1:1)
yielded 64 mg (0.26 mmol, 70%) of lactone 15 as colourless
oil.
1,8a,4,4a,5,6,7,8-Octahydro-7b-(2-hydroxy-isopropyl)-
1,4aa-dimethyl-naphtalen-2(3H)-one (12)
3.7 mL of borane tetrahydrofuran complex solution (1 M)
were added to a solution of alkene 4 (436 mg, 2 mmol) in
dry THF (10 mL) under N2 atmosphere and allowed to stand
for 1 h. Then, 0.3 mL of water, 1.0 mL of NaOH 3N, and
1.0 mL of H2O2 (30%) were added. The mixture was stirred
during 1 h, and then NaCl was added until the solution was
saturated. The mixture was extracted with AcOEt
(5£10 mL), and the organic layer washed with brine.
Chromatography (Hexane:AcOEt, 3:1) afforded alcohol 12
(359 mg, 1.52 mmol, 76%) as colourless gum.
15: [a]2D0ˆ269.8 (c 0.2, CHCl3); IR (KBr)neat
nmax: 1755
(g-lactone), 1640 (ketone a,b-unsaturated) cm21. MS, m/z
(relative intensity), C15H18O3: 246 [M]1 (15), 231
[M2CH3]1 (21), 218 [M2CO]1 (32); dH (200 MHz,
CDCl3): 6.72 (1H, d, Jˆ10 Hz, H-1), 6.23 (1H, d,
Jˆ10 Hz, H-2), 5.21 (1H, d, Jˆ5 Hz, H-6), 2.90 (1H, dq,
Jˆ7, 7 Hz, H-11), 2.02 (3H, s, H-15), 1.75±1.46 (5H, m,
H-7a, H-8a, H-8b, H-9a, H-9b), 1.30 (3H, s, H-14), 1.25
(3H, d, Jˆ7 Hz, H-13). HREIMS: M1, found 246.1253.
C15H18O3 requires 246.1256.
12: [a]2D0ˆ2160.3 (c 0.12, CHCl3); IR (KBr)neat nmax: 3440
(hydroxyl group), 1640 (a,b-unsaturated ketone), 1600
(double bond) cm21
; MS, m/z (relative intensity),
C15H24O2: 236 [M]1 (11), 221 [M2CH3]1 (13), 218 [M2
H2O]1 (2), 203 [M2H2O±CH3]1 (9), 177 [M2C3H7O]1
(100); dH (200 MHz, CDCl3): 3.67 (1H, dd, Jˆ10.5,
3.5 Hz, H-12), 3.45 (1H, dd, Jˆ10.5, 3.5 Hz, H-120), 2.72
(1H, ddd, Jˆ15, 3, 2 Hz, H-2), 2.62±2.35 (3H, m, H-6, H-60,
H-11), 2.19 (1H, brdd, Jˆ15, 7 Hz, H-20), 1.76 (3H, d,
Jˆ1 Hz, H-15), 1.69±1.26 (7H, m, H-1, H-7a, H-8, H-9),
1.21 (3H, s, H-14), 0.95 (3H, d, Jˆ7 Hz, H-13). HREIMS:
M1, found 236.1781. C15H24O2 requires 236.1776.
6b,10a-a-Santonin (16)
Lactone 15 (75 mg, 0.30 mmol) was dissolved in dry THF
(15 mL). A 0.4 M solution of KHMDS (1.5 mL, 0.4 mmol)
in THF was added at 2738C with continuous stirring. The
solution immediately turned red. Triethyl phosphite
(1.5 mL) was added and the mixture was stirred for 1 h.
Then, a current of oxygen was bubbled through the solution
for 1 h and the system was warmed to 2208C. Neutrali-
zation was carefully accomplished by addition of 30%
solution of dry acetic acid in THF (until the colour turned
to yellowish). A Sorensen buffer solution (pHˆ7) was
added and organic solvents and water evaporated under
reduced pressure. The solid was extracted with AcOEt
(5£10 mL) at 508C. The crude extract was chromatographed
(Hexane:AcOEt, 4:1) to give 16 (46 mg, 0.18 mmol, 57%)
as colourless oil.
(2S)-Bromo-1,2-dehydro-6b, 10a, 11b-a-santonin (14)
Alcohol 12 (800 mg, 3.39 mmol) was dissolved in acetone
(40.3 mL) and then Jones' reagent (5.7 mL; 63% CrO3/
H2SO4 cc) was added. After 1 h, water, AcOEt and
Na2CO3 were added until the pH was approximately 4.
The mixture was extracted with AcOEt (5£25 mL), the
organic layer washed with brine, dried with Na2SO4 and
the solvent evaporated under reduced pressure. The mixture
was dissolved in dioxan (30 mL) and small portions of
phenyltrimethylammonium perbromide (2.5 g) and an
excess of Na2CO3 (until an amount is deposited at the
bottom) were added. After 1.5 h, an excess of Na2S2O3
was added and stirred for 30 min. The reaction was
neutralized with a solution of aq. HCl (5%), and extracted
with CHCl3 (5£25 mL) and AcOEt (5£20 mL). After
16: [a]2D0ˆ220.4 (c 0.1, CHCl3); IR (KBr)neat
nmax: 3450
(hydroxyl group), 1790 (g-lactone), 1650 (a,b-unsaturated
ketone) cm21; MS, m/z (relative intensity), C15H18O4: 262
[M]1 (3), 247 [M2CH3]1 (3), 244 [M2H2O]1 (10), 218
[M-CO2]1 (1), 123 (11), 69 (72), 55 (100); dH (200 MHz,
CDCl3): 6.75 (1H, d, Jˆ10 Hz, H-1), 6.21 (1H, d, Jˆ10 Hz,

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F. A. Macõas et al. / Tetrahedron 56 (2000) 3409±3414
3414
H-2), 5.62 (1H, dq, Jˆ7, 1.5 Hz, H-6), 2.92 (1H, ddd, Jˆ7,
7, 7 Hz, H-7), 2.05 (3H, d, Jˆ1.5 Hz, H-15), 1.81±1.79 (1H,
m, H-8a), 1.70±1.48 (3H, m, H-8b, H-9a, H-9b), 1.33 (3H,
s, H-13), 1.28 (3H, s, H-14); dC (100 MHz, CDCl3): 188.3
(s, C-3), 179.6 (s, C-12), 158.0 (d, C-1), 153.6 (s, C-5),
136.8 (s, C-4), 127.2 (d, C-2), 78.5 (d, C-6), 76.8 (s, C-11,
47.4 (d, C-7), 41.4 (s, C-10), 34.6 (t, C-9), 28.9 (q, C-14),
22.2 (q, C-13), 20.1 (t, C-8), 14.4 (q, C-15); HREIMS: M1,
found 262.1201. C15H18O4 requires 262.1205.
[M2HOAng]1, found 244.1091. C15H16O3 requires
244.1089.
Acknowledgements
Â
This research was supported by Direccion General de
Investigacion Cientõ®ca y Tecnica, Spain (DGICYT, Project
Â
Â
Â
PB95-1231). We thank Drs Alan F. Thomas and Sina Escher
Á
from Firmenich S.A., Geneve (Suisse) for providing angelic
acid.
(1)-Decipienin A (1)
To a stirred solution of angelic acid (25 mg, 0.25 mmol) in
dry toluene:DCM (1:1; 3 mL) under argon was added 2,4,6-
trichlorobenzoyl chloride (38.6 mL, 0.25 mmol) and
triethylamine (34.9 mL, 0.25 mmol). The resulting mixture
was stirred for 2 h at 208C and then treated with 16 (10 mg,
0.038 mmol). The mixture was stirred for 4 days at room
temperature and was then diluted with ether (2 mL) and
®ltered. The ®ltrate was concentrated under reduced
pressure and the resulting crude mixture puri®ed by HPLC
using a silica gel column (Hexane:AcOEt, 6:4) to give 1
(4.2 mg, 0.012 mmol, 32%).
References
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1: Colourless crystals, mp 182±1848C; [a]2D0ˆ154.3 (c 0.1,
CHCl3) [lit.6 [a]2D5ˆ154.9 (c 0.2, CHCl3)]; IR (KBr)neat
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d, Jˆ10 Hz, H-2), 6.20 (1H, qq, Jˆ7, 1.5 Hz, H-30), 5.62
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Executive Secretary, International Union of Crystallography, 5
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Â
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