Total synthesis of (±)-zearalanone

Article abstract of DOI:10.1007/s007060170067

A new approach to the macrocyclic lactone zearalanone is described utilizing an alkenol and an arene trifluoromethanesulfonate as starting materials. The key step is a Pd(0)-catalyzed cross-coupling of the arene trifluoromethanesulfonate with a 9-alkyl-9-

Full text of DOI:10.1007/s007060170067

Monatshefte fuÈr Chemie 132, 805±811 (2001)
Total Synthesis of (Æ)-Zearalanonea
Ã
Franz Bracher and JuÈrgen Krauss
È
È
Department Pharmazie ± Zentrum fuÈr Pharmaforschung, Ludwig-Maximilians-Universitat Munchen,
D-81377 MuÈnchen, Germany
Summary. A new approach to the macrocyclic lactone zearalanone is described utilizing an alkenol
and an arene tri¯uoromethanesulfonate as starting materials. The key step is a Pd(0)-catalyzed cross-
coupling of the arene tri¯uoromethanesulfonate with a 9-alkyl-9-borabicyclo[3.3.1]nonane derived
from the alkenol. The title compound is obtained by macrolactonization of a hydroxy acid under
Mitsunobu conditions.
Keywords. Macrocyclic lactones; Hydroboration; Palladium-catalyzed cross-coupling; Zearalanone;
Natural product.
Introduction
In 1962, Stob et al. [1] have isolated the ꢀ-resorcylic lactone zearalenone (1) from
the mycelia of the fungus Giberella zeae (Fusarium graminearum). Later, numerous
related macrocyclic lactones have been isolated from fungi. These lactones and their
semisynthetic derivatives [2] have been shown to exhibit interesting estrogenic,
anabolic, immunomodulating, and antimicrobial properties [3]. (S)-Zearalanone
((S)-2) has ®rst been obtained by catalytic hydrogenation of natural 1 [2]. Later on,
zearalanone (2) has been identi®ed as a metabolite of the fungus Fusarium
reticulatum. The absolute con®guration of this constituent has not been determined
[4]. (R)-Zearalanone ((R)-2) has been prepared in nine steps (2.36% overall yield)
from natural (S)-1 by cleavage of the lactone, inversion of the resulting chiral
secondary alcohol, and relactonization [5]. An eleven-step synthesis of racemic
zearalanone has been described by Hurd et al. [6]. Because of the poor availability
Scheme 1
a
Dedicated to Professor Dr. Eberhard Reimann, Munich, on the occasion of his 65th birthday
Ã
Corresponding author

806
F. Bracher and J. Krauss
of 1 semisynthetic methods do not offer an ef®cient approach to zearalanone.
Therefore, we worked out a new approach to (Æ)-zearalanone (2).
Results and Discussion
The known TBDS ether 3 [7] was prepared from commercially available 5-oxo-
hexanenitrile by reduction with sodium borohydride to give racemic 5-hydroxy-
hexanenitrile and subsequent protection of the secondary alcohol under standard
conditions [7]. A ®rst attempt to convert nitrile 3 to ketone 6 by reaction with pent-
4-enyl magnesium bromide resulted in a very poor yield. Thus, 3 was reduced to
aldehyde 4 with DIBAH [8]. This was reacted with pent-4-enyl magnesium bromide
to alcohol 5 (racemic mixture of diastereomers), which in turn was oxidized to the
racemic ketone 6 under Swern conditions [9]. For further transformations it was
necessary to protect the keto group and to deprotect the hydroxy group of 6. This
could be accomplished in one single operation by dithioacetalization of the carbonyl
group with 1,3-propanedithiol/BF3 [10]. In the course of this transformation the
TBDS protective group of the secondary alcohol was completely removed to give
the hydroxy dithiane 7.
Connection of the aliphatic part of 2 with the aromatic part was performed in a
manner already successfully employed in the total syntheses of the related natural
Scheme 2

(Æ)-Zearalanone
807
products lasiodiplodin [11], curvulin, lunularine, and lunularic acid [12]. In this
method, a terminal ole®n is converted to a terminal organoborane by addition of 9-
borabicylononane [13]. The resulting B-alkyl-BBN-derivative can be subjected to a
palladium-catalyzed cross-coupling reaction with an arene tri¯ate to give the
corresponding alkyl arene. For this purpose we needed the arene tri¯ate 8 which was
conveniently prepared from methyl 2,4,6-trihydroxybenzoate by O,O-dibenzylation
and subsequent esteri®cation with tri¯uoromethanesulfonic anhydride [14]. Thus,
hydroxy ole®ne 7 was treated with two equivalents of BBN. One equivalent of the
borane was consumed by reaction with the hydroxy group, whereas the second
equivalent added to the ole®ne to give a terminal B-alkyl-BBN-derivative. This
product was, without further puri®cation, reacted with the tri¯ate 8, Pd(PPh3)4, and
K2CO3 to give, after aqueous workup, the coupling product 9.
Alkaline hydrolysis of ester 9 gave the hydroxy acid 10 which could be lacto-
nized under Mitsunobu conditions [15] to the macrocyclic lactone 11. Hydrolysis
of the thioacetal group with HgO/BF3 [16] gave O,O-dibenzylzearalanone (12).
Finally, the two benzyl protective groups were removed by hydrogenolysis with
palladium catalyst. The spectroscopic data of the product (Æ)-zearalanone (2) were
in full accordance with those published for the natural product [3]. The overall yield
of our total synthesis of 2 comprising eight steps starting from known aldehyde 4
was 1.2%.
Experimental
General
Elemental analyses were performed on a Carlo Erba CHNO Elemental Analyser. The obtained values
agreed favourably with the calculated ones. FTIR spectra were recorded on a Pye-Unicam PU-9800
spectrometer. NMR spectra were recorded in CDCl3 with TMS as internal standard on a Bruker AM
1
400 NMR spectrometer (400.1 MHz for H, 100.5 MHz for 13C). Mass spectra were recorded on a
Finnigan MAT-8430 spectrometer. Flash column chromatography (FCC) was carried out on Merck
Kieselgel 60 (230±400 mesh). Tetrahydrofuran (THF) was freshly distilled from sodium benzo-
phenone ketyl prior to use.
(Æ)-Zearalanone (2; C18H24O5)
To 0.08 g 12 (0.2 mmol) dissolved under N2 in 1 cm3 ethyl acetate and 10 cm3 methanol, 20 mg Pd/C
(10%) were added, and the mixture was hydrogenated at atmospheric pressure for 4 h. After ®ltration
the organic solvent was evaporated, and the residue was puri®ed by FCC (hexane:ethyl acetate ˆ 4:1)
to give 28 mg (55%) of 2 as a white solid.
‡
M.p.: 211ꢀC (Ref. [3a]: 208ꢀC); MS (70 eV): m=z (%) ˆ 320 (100, M ), 302 (62), 251 (58), 163
1
(88), 125 (66), 112 (56); IR (KBr): ꢁ ˆ 3447, 1793, 1693, 1465, 1210, 1148, 849, 801, 727cm
;
1H NMR (CDCl3, ꢂ, 400 MHz): 1.34 (d, J ˆ 6:2 Hz, 3H, CH3), 1.35±2.10 (m, 16H, 8CH2), 5.20 (m,
1H, CH), 6.25 (d, J ˆ 2:5 Hz, 1H, aromat. CH), 6.30 (d, J ˆ 2:5 Hz, 1H, aromat. CH), 9.15 (s, 1H,
OH), 12.01 (s, 1H, OH) ppm; 13C NMR (CDCl3, ꢂ, 100MHz): 23.19 (CH3), 23.20 (CH2), 23.24
(CH2), 28.21 (CH2), 32.32 (CH2), 35.73 (CH2), 36.70 (CH2), 38.25 (CH2), 44.38 (CH2), 64.72 (CH),
101.97 (aromat. CH), 104.69 (quart. C), 111.94 (aromat. CH), 149.39 (quart. C), 163.41 (quart. C),
166.91 (quart. C), 172.50 (COO), 211.38 (C=O) ppm.

808
F. Bracher and J. Krauss
(Æ)-2-tert.-Butyldimethylsilyloxy-10-undecen-6-ol (5; C17H36O2Si; mixture of diastereomers)
Magnesium (310 mg, 13 mmol) and one crystal of I2 were suspended in 5 cm3 anhydrous diethyl
ether, and a solution of 0.97 g 1-bromopent-4-ene (6.5mmol) in 5 cm3 diethyl ether was added
dropwise. The mixture was re¯uxed for 1 h. Then, 830 mg (3.8 mmol) 4 were dissolved in 5 cm3
diethyl ether, and the solution of the Grignard reagent was added dropwise at room temperature. After
1 h the reaction was quenched with saturated NH4Cl solution. The organic layer was separated, and
the aqueous phase was extracted with diethyl ether (2 Â 15 cm3). The combined organic layers were
dried over Na2SO4, and the solvent was evaporated. The residue was puri®ed by FCC (hexane:ethyl
acetate ˆ 20:1) to give 615 mg (54%) of 5 as a colourless liquid.
‡
MS (CI, NH3): m=z (%) ˆ 301 (100, M ‡ 1), 283 (4), 169 (20), 151 (6), 109 (4); IR (NaCl/®lm):
ꢁ ˆ 3359, 3077, 2930, 2858, 1641, 1462, 1374, 1254, 1135, 910, 835, 774 cm 1; 1H NMR (CDCl3, ꢂ,
400 MHz): 0.04 (s, 6H, 2CH3), 0.84 (s, 9H, 3CH3), 1.07 (d, J ˆ 6:1 Hz, 3H, CH3), 1.20±1.54 (m,
10H, 5CH2), 2.02±2.04 (m, 2H, CH2), 3.50±3.60 (m, 1H, CH), 3.74 (tq, J ˆ 5:7 Hz, J ˆ 5:9 Hz, 1H,
CH), 4.90 (m, 1H, CH2=), 4.96 (ddd, J ˆ 1:8 Hz, J ˆ 17:2 Hz, J ˆ 1:8 Hz, 1H, CH2=), 5.76 (ddd,
J ˆ 6:7 Hz, J ˆ 10:3 Hz, J ˆ 17:2 Hz, 1H, -CH=) ppm; 13C NMR (CDCl3, ꢂ, 100 MHz): 4.8
(CH3), 4.5 (CH3), 18.06 (quart. C), 21.64 (CH2), 21.8 (CH2), 23.68 (CH3), 23.74 (CH3), 24.82
(CH2), 24.82 (CH2), 24.84 (CH2), 25.84 (3CH3), 33.67 (CH2), 36.74 (CH2), 37.41 (CH2), 37.50
(CH2), 39.55 (CH2), 39.61 (CH2), 68.45 (CH), 68.51 (CH), 71.62 (CH), 71.64 (CH), 114.49 (H2C=),
138.65 (=CH-) ppm.
(Æ)-10-(tert.-Butyldimethylsilyloxy)-1-undecen-6-one (6; C17H34O2Si)
A solution of 0.20 cm3 oxalyl chloride (2.0 mmol) in 1 cm3 CH2Cl2 was added dropwise to a solution
of 0.40 cm3 DMSO (5.6 mmol) in 1 cm3 CH2Cl2 under N2 at 70ꢀC. After 30 min, a solution of
500 mg (1.7 mmol) 5 in 1 cm3 CH2Cl2 was added, and the resulting mixture was stirred for 30 min.
Then 1 cm3 of triethylamine was added, and the reaction was allowed to warm up to room tem-
perature. After addition of 5 cm3 H2O the organic layer was separated, the aqueous phase was
extracted with CH2Cl2 (2 Â 5 cm3), and the combined organic layers were dried over Na2SO4. The
solvent was evaporated, and the residue was puri®ed by FCC (hexane:ethyl acetate ˆ 20:1) to give
360 mg (72%) of 6 as a colourless oil.
‡
MS (CI, NH3): m=z (%) ˆ 299 (M ‡ 1, 58), 265 (46), 202 (35), 197 (50), 167 (100); IR (NaCl/
®lm): ꢁ ˆ 2953, 2929, 2904, 2857, 1715, 1641, 1471, 1462, 1410, 1374, 1254, 1215, 1137, 1005, 836,
1
775 cm
;
1H NMR (CDCl3, ꢂ, 400 MHz): 0.04 (s, 6H, 2CH3), 0.88 (s, 9H, 3CH3), 1.12 (d,
J ˆ 6:0 Hz, 3H, CH3), 1.21±1.66 (m, 6H, 3CH2), 2.00 (dt, J ˆ 7:0 Hz, J ˆ 6:9 Hz, 2H, CH2), 2.34
(t, J ˆ 7:4 Hz, 2H, CH2), 2.35 (t, J ˆ 7:4 Hz, 2H, CH2), 3.74 (tq, J ˆ 6:0 Hz, J ˆ 6:0 Hz, 1H, CH),
4.93 (m, 2H, H2C=), 5.71 (ddt, J ˆ 6:9 Hz, J ˆ 10:3 Hz, J ˆ 17:0 Hz, 1H, =CH-) ppm; 13C NMR
(CDCl3, ꢂ, 100 MHz): 4.73 (CH3), 4.38 (CH3), 20.16 (CH2), 18.10 (quart. C), 22.80 (CH2), 23.75
(CH3), 25.90 (3CH3), 33.14 (CH2), 39.13 (CH2), 41.76 (CH2), 42.90 (CH2), 68.34 (CHOH), 115.17
(CH2=), 137.98 (CH=), 210.79 (C=O) ppm.
(Æ)-2-(4-Hydroxypentyl)-2-(4-pentenyl)-1,3-dithiane (7; C14H26OS2)
To 360mg (1.5 mmol) 6 dissolved in 5 cm3 MeOH at 0ꢀC, 2 cm3 BF3 ÁEt2O and 0.75 cm3 (19 mmol)
1,3-propanedithiol were added. The mixture was allowed to warm up to room temperature with
stirring, and the solvent was evaporated. The residue was puri®ed by FCC (hexane:ethyl acetate ˆ
5:1) to give 160mg (39%) of 7 as a pale yellow oil.
‡
MS (70 eV): m=z (%) ˆ 274 (50, M ), 205 (48), 199 (65), 187 (100), 167 (86), 145 (84), 106 (90);
IR (NaCl/®lm): ꢁ ˆ 3399, 3392, 3075, 2935, 2909, 2865, 1640, 1456, 1422, 1273, 1131, 993,
909 cm 1; 1H NMR (CDCl3, ꢂ, 400MHz): 1.20 (d, J ˆ 6:1 Hz, 3H, CH3), 1.24±1.97 (m, 12H, 6CH2),
2.08 (dt, J ˆ 6:9 Hz, J ˆ 7:2 Hz, 2H, CH2), 2.80 (dd, J ˆ 3:6 Hz, J ˆ 3:9 Hz, 4H, 2CH2), 3.83 (tq,
J ˆ 6:2 Hz, J ˆ 6:1 Hz, 1H, CH), 4.98 (ddt, J ˆ 1:8 Hz, J ˆ 17:1 Hz, J ˆ 1:7 Hz, 1H, HC=), 5.04

(Æ)-Zearalanone
809
(ddt, J ˆ 1:0 Hz, J ˆ 1:9 Hz, 10.1 Hz, 1H, HC=), 5.80 (ddt, J ˆ 6:6 Hz, J ˆ 10:1 Hz, J ˆ 17:1 Hz,
1H, -CH=) ppm; 13C NMR (CDCl3, ꢂ, 100MHz): 20.46 (CH2), 23.39 (CH2), 23.58 (CH3), 25.49
(CH2), 26.02 (CH2), 26.02 (CH2), 33.71 (CH2), 37.59 (CH2), 38.23 (CH2), 39.33 (CH2), 67.85 (CH),
114.90 (quart. C), 115.03 (CH2=), 138.32 (CH=) ppm.
(Æ)-Methyl 2,4-bis-(benzyloxy)-6-(5-(2-(4-hydroxypentyl)-1,3-dithian-2-yl)-pentyl)-benzoate
(9; C36H46O5S2)
An oven-dried ¯ask equipped with a re¯ux condenser and a septum inlet was ¯ushed with N2 and
charged with a solution of 13.0 cm3 (6.5 mmol) 0:5 M BBN in THF; then, 0.84 g (3.1 mmol) 7 were
added at 0ꢀC. The mixture was warmed up slowly to room temperature and stirred for further 4±6h to
give a solution of the B-alkyl-BBN derivative.
To the above solution, 4 cm3 dioxane, 5 cm3 H2O, 1.1 g (5.2 mmol) powdered K3PO4, 100 mg
(0.09 mmol) Pd(PPh3)4, and 1.45 g (2.9mmol) aryl tri¯ate 8 [14] were added. The mixture was heated
at 95ꢀC for 16 h, extracted with diethyl ether, and the organic layer was concentrated in vacuo. The
residue was puri®ed by FCC (hexane:ethyl acetate ˆ 1:1) to give 1.06 g (55%) of 9 as a pale yellow oil.
‡
MS (70 eV): m=z (%)ˆ 622 (8, M ), 620 (26), 604 (44), 497 (58), 311 (100), 181 (70); IR (NaCl/
®lm): ꢁ ˆ 3488, 3474, 3459, 2932, 2863, 1725, 1601, 1454, 1432, 1376, 1272, 1160, 1098, 737,
698 cm 1; 1H NMR (CDCl3, ꢂ, 400MHz): 1.17 (d, J ˆ 6:3 Hz, 3H, CH3), 1.19±1.69 (m, 10H, 5CH2),
1.82±1.92 (m, 6H, 3CH2), 2.57 (t, J ˆ 7:8 Hz, 2H, CH2), 2.77 (t, J ˆ 5:6 Hz, 4H, 2CH2), 3.79 (m,
1H, CH), 3.85 (s, 3H, OCH3), 5.01 (s, 2H, CH2O), 5.02 (s, 2H, CH2O), 6.43 (s, 2H, aromat. CH),
7.27±7.40 (m, 10H, aromat. CH) ppm; 13C NMR (CDCl3, ꢂ, 100 MHz): 20.48 (CH2), 23.55 (CH3),
23.82 (CH2), 25.47 (CH2), 25.96 (CH2), 26.21 (CH2), 29.44 (CH2), 30.83 (CH2), 33.70 (CH2), 38.11
(CH2), 38.14 (CH2), 39.25 (CH2), 52.04 (OCH3), 67.68 (CHOH), 70.05 (CH2O), 70.37 (CH2O),
98.45 (aromat. CH), 107.34 (aromat. CH), 107.34 (aromat. CH), 116.95 (quart. C), 126.85 (aromat.
CH), 127.50 (aromat. CH), 127.74 (aromat. CH), 128.07 (aromat. CH), 128.43 (aromat. CH), 128.58
(aromat. CH), 136.51 (quart. C), 136.69 (quart. C), 142.82 (quart. C), 157.06 (quart. C), 160.38 (quart.
C), 168.79 (C=O) ppm.
(Æ)-2,4-Bis-(benzyloxy)-6-(5-(2-(4-hydroxypentyl)-1,3-dithian-2-yl)-pentyl)-benzoic acid
(10; C35H44O5S2)
Methyl ester 9 (1.06 g, 1.7 mmol) was dissolved in 30 cm3 EtOH and 30 cm3 aqueous 8 M KOH. The
solution was re¯uxed for 30 h, 60 cm3 4 M HCl were added, and the solution was extracted with
diethyl ether. The organic layer was evaporated to give 980mg (95%) of 10 as a yellow oil.
‡
MS (70 eV): m=z (%)ˆ 608 (0.2, M ), 457 (2), 367 (3), 106 (62), 91 (100); IR (NaCl/®lm):
1
ꢁ ˆ 2932, 2863, 1713, 1602, 1497, 1454, 1376, 1320, 1279, 1162, 1112, 908, 831 cm 1; H NMR
(CDCl3, ꢂ, 400MHz): 1.17 (d, J ˆ 8:1 Hz, 3H, CH3), 1.20±2.01 (m, 14H, 7CH2), 2.57±2.82 (m, 4H,
2CH2S), 3.83 (m, 1H, CH), 5.00 (s, 2H, CH2O), 5.05 (s, 2H, CH2O), 6.44 (d, J ˆ 2:1 Hz, 1H, aromat.
CH), 6.45 (d, J ˆ 2:1 Hz, 1H, aromat. CH), 7.20±7.85 (m, 10H, aromat. CH) ppm; 13C NMR (CDCl3,
ꢂ, 100 MHz): 20.32 (CH2), 23.37 (CH3), 23.43 (CH2), 25.55 (CH2), 25.96 (CH2S), 29.14 (CH2),
30.62 (CH2), 33.73 (CH2), 37.87 (CH2), 37.96 (CH2), 38.98 (CH2), 68.04 (CHO), 70.07 (CH2O),
70.76 (CH2O), 98.56 (aromat. CH), 107.99 (aromat. CH), 115.99 (quart. C), 127.09 (aromat. CH),
127.52 (aromat. CH), 127.91 (aromat. CH), 128.12 (aromat. CH), 128.54 (aromat. CH), 128.61
(aromat. CH), 136.30 (quart. C), 136.42 (quart. C), 144.32 (quart. C), 157.36 (quart. C), 160.56 (quart.
C), 170.21 (COOH) ppm.
(Æ)-14,16-Bis-(benzyloxy)-3,4,5,6,7,8,9,10,11,12-decahydro-3-methyl-7,7-trimethylenedithiobenzox-
acyclotetradecin-1-one (11; C35H42O4S2)
0.50 g (0.8mmol) PPh3 were dissolved in 290 cm3 toluene under N2. 0.4 cm3 (2.6 mmol) diethyl
azodicarboxylate (DEAD) were added to the solution, and the mixture was stirred for 20 min. Over a

810
F. Bracher and J. Krauss
period of 6 h, one half of a solution of 500 mg (0.8 mmol) 10 in 10 cm3 THF:toluene ˆ 1:4 was added
with a syringe pump. After stirring for additional 10 h, 0.35 g (1.3 mmol) PPh3 and 0.2 cm3
(1.3 mmol) DEAD were added; the rest of the solution of the hydroxy acid was added over 6 h. After
stirring for further 10 h the organic solvent was evaporated, and the residue was puri®ed by FCC
(hexane:ethyl acetate ˆ 20:3) to give 200 mg (42%) of 11 as a white solid.
‡
M.p.: 64ꢀC; MS (70 eV): m=z (%) ˆ 590 (22, M ), 490 (24), 91 (100); IR (KBr): ꢁ ˆ 2934, 2862,
1
1715, 1602, 1497, 1455, 1378, 1268, 1162, 1097, 737, 698 cm 1; H NMR (CDCl3, ꢂ, 400MHz):
1.12 (d, J ˆ 6:2 Hz, 3H, CH3), 1.17±2.0 (m, 18H, 9CH2), 2.73 (m, 4H, 2CH2S), 4.99 (s, 4H, 2CH2O),
5.12 (m, 1H, CH), 6.43 (d, J ˆ 2:1 Hz, 1H, aromat. CH), 6.46 (d, J ˆ 2:1 Hz, 1H, aromat. CH), 7.25±
7.69 (m, 10H, aromat. CH) ppm; 13C NMR (CDCl3, ꢂ, 100 MHz): 18.39 (CH2), 20.16 (CH3), 21.18
(CH2), 25.39 (CH2), 25.90 (CH2), 25.95 (CH2), 26.72 (CH2), 29.52 (CH2), 31.18 (CH2), 34.96 (CH2),
36.31 (CH2), 36.24 (CH2), 69.97 (CH2O), 70.13 (CH), 70.39 (CH2O), 98.14 (aromat. CH), 106.67
(aromat. CH), 117.87 (quart. C), 127.45 (aromat. CH), 127.54 (aromat. CH), 127.87 (aromat. CH),
127.97 (aromat. CH), 128.29 (aromat. CH), 128.32 (quart. C), 128.51 (aromat. CH), 136.43 (quart. C),
136.61 (quart. C), 142.08 (quart. C), 156.90 (quart. C), 160.27 (quart. C), 168.14 (C=O) ppm.
(Æ)-14,16-Bis-(benzyloxy)-3,4,5,6,7,8,9,10,11,12-decahydro-3-methylbenzoxacyclotetradecin-
1,7-dione ((Æ)-O,O-dibenzylzearalanone) (12; C32H36O5)
To 0.38 g (0.64 mmol) 11 dissolved in 20 cm3 THF:H2O ˆ 7:3, 480 mg (2.2 mmol) red HgO and
260 mg (1.83 mmol) BF3 Á Et2O were added. The suspension was stirred for 30 min and extracted ®rst
with CH2Cl2 and then with ethyl acetate. The combined organic layers were dried over Na2SO4, and
the solvent was evaporated. The residue was puri®ed by FCC (hexane:ethyl acetate ˆ 5:1) to give
210 mg (66%) of 12 as pale yellow crystals.
‡
M.p.: 78ꢀC; MS (70 eV): m=z (%) ˆ 500 (M , 14), 482 (4), 424 (10), 409 (4), 272 (30), 202 (38),
1
91 (100); IR (KBr): ꢁ ˆ 2960, 1720, 1610, 1460, 1440, 1270, 1170, 1080, 960, 850, 740, 700cm
;
1H NMR (CDCl3, ꢂ, 400 MHz): 1.13 (d, J ˆ 6:3 Hz, 3H, CH3), 1.11±2.63 (m, 16H, 8CH2), 4.32 (m,
1H, CH), 4.99 (d, J ˆ 3:0 Hz, 2H, CH2O), 5.03 (s, 2H, CH2O), 6.42 (d, J ˆ 2:1 Hz, 1H, aromat. CH),
6.46 (d, J ˆ 2:1 Hz, 1H, aromat. CH), 7.07±7.43 (m, 10H, 10 aromat. CH) ppm; 13C NMR (CDCl3, ꢂ,
100 MHz) 19.19 (CH3), 19.83 (CH2), 23.28 (CH2), 27.67 (CH2), 30.74 (CH2), 33.72 (CH2), 34.42
(CH2), 38.74 (CH2), 70.10 (CH2O), 70.34 (CH), 70.51 (CH2O), 98.32 (aromat. CH), 107.18 (aromat.
CH), 117.44 (aromat. CH), 127.52 (aromat. CH), 127.56 (aromat. CH), 127.97 (aromat. CH), 128.10
(aromat. CH), 128.40 (aromat. CH), 128.62 (aromat. CH), 136.45 (quart. C), 136.59 (quart. C), 142.57
(quart. C), 157.07 (quart. C), 160.36 (quart. C), 167.96 (COO), 212.49 (C=O) ppm.
Acknowledgements
We thank the Fonds der Chemischen Industrie for ®nancial support.
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(Æ)-Zearalanone
811
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[15] a) Hughes DL (1992) Org React, vol 42. Wiley, New York, p 335; b) Mitsunobu O (1981)
Synthesis 1
[16] Bracher F, Litz T (1995) Arch Pharm 328: 235
Received December 29, 2000. Accepted February 5, 2001