An Efficient Asymmetric Synthesis of Tarchonanthuslactone

Article abstract of DOI:10.1002/ejoc.200300412

An efficient and straightforward ten-step asymmetric synthesis of the polyketide tarchonanthuslactone (1) in good overall yield (21% starting from chloro lactone 5) and with excellent diastereomeric and enantiomeric excesses (de, ee ≥ 96%) is described. The new synthetic route is based on the α,β-unsaturated δ-lactone building block 5, available in enantiopure form (ee > 99%) through an enzymatic procedure, and its conversion into methyl ketone 11 by an Umpolung strategy. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300412

FULL PAPER
An Efficient Asymmetric Synthesis of Tarchonanthuslactone
Dieter Enders*[a] and Daniel Steinbusch[a]
Dedicated to Professor Manfred T. Reetz on the occasion of his 60th birthday
Keywords: Amino nitriles / Asymmetric synthesis / Lactones / Natural products / Polyketides
An efficient and straightforward ten-step asymmetric syn-
thesis of the polyketide tarchonanthuslactone (1) in good
overall yield (21% starting from chloro lactone 5) and with
excellent diastereomeric and enantiomeric excesses (de, ee
Ն 96%) is described. The new synthetic route is based on
the α,β-unsaturated δ-lactone building block 5, available in
enantiopure form (ee Ͼ 99%) through an enzymatic proced-
ure, and its conversion into methyl ketone 11 by an Umpo-
lung strategy.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
demonstrated by us in the total syntheses of the natural
products (S)-argentilactone, (S)-goniothalamin,[9] and cally-
statin A.[10] Here we report an efficient, diastereo- and en-
antioselective synthesis of the title natural product tarchon-
anthuslactone (1) from the versatile δ-lactone building
block 5.
Many natural products with different biological activities,
such as antitumour, antibacterial, antifungal or immunos-
uppressive properties, possess α,β-unsaturated δ-lactone
moieties as an important structural feature. The α,β-unsatu-
rated δ-lactone functionality is presumed to be responsible
for the biological activities, due to its ability to act as a
Michael acceptor, enabling these molecules to bind to a tar-
get enzyme.
Results and Discussion
One of these natural products, tarchonanthuslactone (1),
was isolated by Bohlmann in 1979 from the leaves of a tree
Our retrosynthetic analysis of tarchonanthuslactone (1)
called Tarchonanthus trilobus.[1] Later, Nakata and co-work- is shown in Scheme 1. The target molecule can be divided
ers were able to assign the compound’s absolute configura- into the chiral alcohol 2 and the aromatic acid 3 by saponi-
tion by carrying out the first asymmetric synthesis of tar- fication of the ester functionality. The secondary alcohol 2
chonanthuslactone (1),[2a] and Hsu et al. found that 1 low- should be accessible by a syn-selective reduction of methyl
ers the plasma glucose levels in diabetic rats as an import- ketone 4, which should in turn be available from chloro
ant biological activity.[3] This important activity and the lactone 5. The aromatic acid 3 can be easily prepared from
potential to transfer this application to human beings made caffeic acid by application of standard hydrogenation and
tarchonanthuslactone (1) a challenging target of several to- protection procedures.
tal syntheses.[2aϪ2f]
It has recently been demonstrated that the NADP-depen-
With regard to the common structural feature in a num- dent alcohol dehydrogenase of Lactobacillus brevis
ber of bioactive natural products, the development of new (recLBADH) can be utilised for the regio- and enantioselec-
synthetic strategies towards this α,β-unsaturated δ-lactone tive reduction of the 5-keto functionality of tert-butyl 6-
moiety should open up access to several natural products, chloro-3,5-dioxohexanoate (6).[8] After a second reduction
such as tetrahydrolipstatin,[4] (ϩ)-strictifolione,[5] fostrie- of the carbonyl group at the 3-position, cyclisation and de-
cin,[6] or the cryptocarya family.[7] With the development of hydration could be accomplished by treatment with p-tolu-
an efficient asymmetric synthesis of both enantiomers of 6- enesulfonic acid (pTsOH) to furnish the α,β-unsaturated
chloromethyl-5,6-dihydropyran-2-one (5), a synthetic equiv- chloro lactone 5. The enantiomeric chloro lactone ent-5 can
alent of the lactone moiety could be provided.[8] The versa- also be synthesized in good yield and with a very good en-
tility of the δ-lactone building block 5 has already been antiomeric excess of 94% by use of the same methodology,
but in the presence of bakerЈs yeast as biocatalyst for the
[a]
reduction step (Scheme 2).[8] The enantiomeric excesses of
Institut für Organische Chemie, RWTH Aachen
Professor-Pirlet-Straße 1, 52074 Aachen (Germany)
compounds 5 and ent-5 were determined by analytical
Fax: (internat.) ϩ49-(0)241-8092127
E-mail: enders@rwth-aachen.de
4450
HPLC on a chiral stationary phase.
DOI: 10.1002/ejoc.200300412
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 4450Ϫ4454

An Efficient Asymmetric Synthesis of Tarchonanthuslactone
FULL PAPER
our synthesis, this stereocenter is lost, so there was no need
to force the acetalisation reaction to complete diastereosel-
ectivity.
However, efforts to convert the chloride 7 directly into
the corresponding iodide 9 by a common Finkelstein reac-
tion did not succeed at all.[12] It was therefore necessary
first to synthesise the alcohol 8 and then to convert it into
iodide 9. The chloride 7 was transformed into its corre-
sponding acetate by treatment with tetrabutylammonium
acetate (TBAA) in N-methylpyrrolidone (NMP), and this
was then converted into alcohol 8 by basic hydrolysis.[9] The
yield of this two-step procedure was 93%. Direct iodination
of alcohol 8 by treatment with triphenylphosphane, imidaz-
ole and iodine furnished the known compound 9 in a good
yield of 82% (Scheme 2).[11,13]
The carbonyl group of the methyl ketone 4 could easily
be introduced by the α-amino nitrile alkylation method-
ology and subsequent hydrolysis of the resulting α-amino
nitrile product (Scheme 3).[14aϪ14g] The known acetaldehyde
α-amino nitrile 10 was therefore deprotonated with lithium
diisopropylamide (LDA) in tetrahydrofuran (THF).[15]
Treatment with iodide 9 yielded the corresponding α-alky-
lation product, which was observed by NMR analysis of
the crude product. During purification by column chroma-
tography on silica gel, hydrolysis of the alkylated α-amino
nitrile product occurred and the methyl ketone 4 could be
directly isolated in a yield of 83% without the usual treat-
ment with aqueous silver() nitrate or copper() sulfate
(Scheme 3).
Scheme 1. Retrosynthetic analysis of tarchonanthuslactone (1)
The chiral alcohol 2 was accessible by a chelate-con-
trolled syn-selective reduction of the carbonyl group of
methyl ketone 4 by treatment with -selectride as reducing
agent in THF at Ϫ78 °C.[16a][16b] The secondary alcohol 2
was then directly treated with the doubly TBS-protected
acid 3 in the presence of dicyclohexylcarbodiimide (DCC)
and 4-(dimethylamino)pyridine (DMAP) without any
further purification to yield ester 11. Acid 3 had previously
been synthesized starting from caffeic acid by hydrogen-
ation and TBS-protection by a literature method.[2d] The
yield of the reduction/esterification procedure was 72% and
Scheme 2. Reagents: (a) recLBADH, cat. NADPϩ, iPrOH, pH 5.5
buffer; (b) 1. NaBH4, EtOH, 0 °C; 2. cat. pTsOH, toluene, room
temp., 14 h, 120 °C, 4 h;[8] (c) 1. DIBAL-H, CH2Cl2, Ϫ78 °C; 2.
iPrOH, PPTS, C6H6, 80 °C;[9] (d) TBAA, NMP, 85 °C; (e) K2CO3,
MeOH, room temp.;[9] (f) PPh3, imidazole, I2, Et2O/CH3CN, 0 °C
a diastereomeric excess of only 43% was determined by 13
C
NMR analysis. Obviously, the reduction of methyl ketone
4 (de ϭ 85%) did not occur with complete diastereoselec-
tivity. For this reason, the reduction was repeated in the
Because of the distinct indication of the sensitivity of α,β- same manner but at lower temperature (Ϫ100 °C) and in
unsaturated δ-lactone 5 towards decarboxylation in the co- highly diluted solution. This time, NMR spectroscopic
urse of the (S)-argentilactone and (S)-goniothalamin synth- analysis of the ester 11 showed a diastereomeric excess of
eses, the lactone moiety was protected by reduction and 85%, indicating that the carbonyl reduction had occurred
subsequent acetalization. This instability was also reported with virtually complete diastereoselectivity.
by Lichtenthaler et al., who used a similar lactone in their
In order to regenerate the α,β-unsaturated δ-lactone moi-
studies towards the total synthesis of (ϩ)-anamarine.[11] ety, the ester 11 was treated with pyridinium chlorochro-
The lactone moiety was therefore reduced with diisobutyl- mate (PCC) in dichloromethane to provide lactone 12 in an
aluminium hydride (DIBAL-H) in dichloromethane at low acceptable yield of 66% and with a diastereomeric excess
temperature, followed by pyridinium p-toluenesulfonate greater than 96%. Possible racemization could be ruled out,
(PPTS) catalysed acetalization to provide the mixed acetal because all analytical data, including the optical rotation of
7 in a good yield of 76% over two steps and with a dia- TBS-protected tarchonanthuslactone (12), corresponded to
[2d]
stereomeric excess of 85%.[9] As the lactone functionality those reported by Solladie et al.
Finally, deprotection of
´
´
has to be recovered by oxidation in one of the last steps of the aromatic hydroxy groups according to Solladie et al. by
Eur. J. Org. Chem. 2003, 4450Ϫ4454
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4451

D. Enders, D. Steinbusch
FULL PAPER
Scheme 3. Reagents: (a) LDA, THF, 0 °C; 9, Ϫ78 °C to room temp.; SiO2; (b) 1. -Selectride, CH2Cl2, Ϫ100 °C to room temp.; 2. DCC,
DMAP, 3, CH2Cl2, room temp.; c) PCC, CH2Cl2, room temp.; (d) TBAF, benzoic acid, THF, room temp.
ous layer with diethyl ether or dichloromethane, (c) drying of the
combined organic layers with MgSO4, and (d) removal of the sol-
vent under reduced pressure. The compositions of the stereo-
isomeric mixtures were determined by 13C NMR spectroscopy.
treatment of TBS-protected tarchonanthuslactone (12) with
tetrabutylammonium fluoride (TBAF) and benzoic acid in
THF furnished the target molecule tarchonanthuslactone
(1) in a good yield of 87%.[2d] The synthesised title com-
pound showed the same optical rotation ([α]2D8 ϭ Ϫ80.8,
c ϭ 0.4, CHCl3) and analytical data as the natural product
Iodide 9: Imidazole (363 mg, 5.3 mmol), triphenylphosphane
(1.322 g, 5.0 mmol), and iodine (949 mg, 3.7 mmol) were added at
isolated from nature by Bohlmann et al.[1] or as synthesized 0 °C to a solution of alcohol 8 (496 mg, 2.9 mmol) in a mixture of
[2d]
diethyl ether and acetonitrile (1.5:1.0, 62 mL). After stirring for
24 h at this temperature, the reaction mixture was diluted with di-
ethyl ether (15 mL) and washed with Na2S2O3 (10% wt. solution
in water, 15 mL) and brine (15 mL). Drying with MgSO4, filtration,
and purification by column chromatography (PE/E, 8:1) gave
664 mg (82%) of iodide 9 as a colourless oil. Rf ϭ 0.70 (PE/E, 4:1).
[α]2D3 ϭ ϩ3.9 (c ϭ 1.11, CHCl3). IR: ν˜ ϭ 2969, 2924, 2896, 1180,
´
by Solladie and co-workers.
Conclusion
An efficient and straightforward diastereo- and enanti-
oselective synthesis of the polyketide natural product tar-
chonanthuslactone (1), based on the enantiomerically pure
1
1126, 1100, 1027 cmϪ1. H NMR: δ ϭ 1.19 (d, J ϭ 6.2 Hz, 3 H,
CHCH3CH3), 1.26 (d, J ϭ 6.2 Hz, 3 H, CHCH3CH3), 1.95Ϫ2.21
δ-lactone building block 5, has been developed. A ten-step (m, 2 H, CHϭCHCH2), 3.23 (m, 2 H, CH2I), 3.96 (m, 1 H,
CH2CHO), 4.15 [sept, J ϭ 6.2 Hz, 1 H, CH(CH3)2], 5.11 (m, 1 H,
OCHO), 5.72 (m, 1 H, OCHCHϭCH), 5.99 (m, 1 H, OCHCHϭ
CH) ppm. 13C NMR: δ ϭ 9.0 (CH2I), 21.5 (CHCH3CH3), 23.8
(CHCH3CH3), 30.8 (CHϭCHCH2), 66.0 (CH2CHO), 68.9
[CH(CH3)2], 92.8 (CHϭCHCH), 126.1 (CHϭCHCH2), 127.6
(CHϭCHCH2) ppm. MS: m/z (%) ϭ 183 (100) [Mϩ Ϫ 99], 157 (6),
153 (5), 152 (17), 152 (17), 151 (5), 149 (7), 141 (5), 139 (22), 115
(6), 113 (11), 111 (7), 109 (6), 108 (8), 107 (13), 99 (5), 97 (10), 96
(10), 95 (10), 85 (9), 71 (15), 69 (16), 58 (10), 57 (26), 55 (14),
51 (14).
synthesis, involving a nucleophilic acylation through α-am-
ino nitrile alkylation to obtain the methyl ketone 4 and its
diastereoselective, chelate-controlled reduction, delivered
the diastereo- and enantiomerically pure title compound in
a good overall yield of 21%. Thanks to the availability of
both enantiomers of the chloro lactone 5 through enzymatic
reduction of tert-butyl 6-chloro-3,5-dioxohexanoate (6), the
enantiomer of tarchonanthuslactone should also be access-
ible by the described procedure.
These analytical data correspond to those reported.[11]
Experimental Section
Methyl Ketone 4: n-Butyllithium (15% wt. solution in n-hexane,
1.2 mL, 2.0 mmol) was added dropwise at 0 °C to a solution of
diisopropylamine (198 mg, 2.0 mmol) in THF (14 mL). After the
mixture had been stirred for 30 min at this temperature, amino ni-
General Remarks: All solvents were dried and purified prior to use.
All reactions were carried out under atmospheres of argon. Col-
umn chromatography: Merck silica gel 60, 0.040Ϫ0.063 mm trile 10 (194 mg, 2.0 mmol) was added. After stirring for another
(230Ϫ400 mesh) (E ϭ diethyl ether, PE ϭ n-pentane). Optical ro- 30 min at this temperature, the reaction mixture was cooled to Ϫ78
tation values: PerkinϪElmer P 241; solvents Merck Uvasol quality. °C. After slow addition of a solution of iodide 9 (460 mg,
IR: PerkinϪElmer FT/IR 1750. NMR: Varian VXR 300, Gemini 1.6 mmol) in THF (14 mL), the reaction mixture was stirred for an
300, and Inova 400, TMS as internal standard. MS: Finnigan MAT additional 16 h and was then allowed to warm to room tempera-
212 and Finnigan SSQ 7000 (70 eV). Microanalyses: Elementar va-
rio EL. THF was dried by distillation from Na/Pb/benzophenone
ture. The reaction was quenched by addition of a saturated aqueous
solution of NaHCO3. The usual workup gave a residue, which was
under an atmosphere of argon. Dichloromethane was distilled from purified by column chromatography (PE/E, 4:1) to give 267 mg
calcium hydride under an atmosphere of argon. ‘‘Usual workup’’
means: (a) isolation of the organic layer, (b) extraction of the aque-
(83%) of methyl ketone 4 as a colourless oil. Rf ϭ 0.57 (PE/E, 1:1).
[α]2D3 ϭ Ϫ17.8 (c ϭ 1.02, CHCl3). IR: ν˜ ϭ 2971, 1381, 1127, 1102,
4452
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Eur. J. Org. Chem. 2003, 4450Ϫ4454

An Efficient Asymmetric Synthesis of Tarchonanthuslactone
1085, 1022 cmϪ1 1H NMR: δ ϭ 1.17 (d, J ϭ 6.1 Hz, 3 H,
FULL PAPER
CHCl3). 1H NMR: δ ϭ 0.18 [s, 6 H, Si(CH3)2], 0.19 [s, 6 H,
.
CHCH3CH3), 1.24 (d, J ϭ 6.1 Hz, 3 H, CHCH3CH3), 2.02 (m, 2 H, Si(CH3)2], 0.98 (s, 9 H, tBu), 0.99 [s, 9 H, C(CH3)3], 1.20 (d, J ϭ
CHϭCHCH2), 2.21 [s, 3 H, C(O)CH3], 2.52 (dd, J ϭ 15.5/4.5 Hz, 1 5.8 Hz, 3 H, CHCH3), 1.94 (m, 1 H, CHϭCHCHH), 2.15 (m, 1
H, OCHCHH), 2.70 (dd, J ϭ 15.5/8.2 Hz, 1 H, OCHCHH), 3.95
H, CHϭCHCHH), 2.25Ϫ2.40 (m, 2 H, CH2CHCH3), 2.56 (t, J ϭ
(q, J ϭ 6.2 Hz, 1 H, OCHCH2), 4.41 [sept, J ϭ 4.6 Hz, 1 H, 7.6 Hz, 2 H, CH2Ph), 2.81 [t, J ϭ 7.6 Hz, 2 H, C(O)CH2], 4.42 (m,
CH(CH3)2], 5.03 (d, J ϭ 2.7 Hz, 1 H, CHϭCHCH), 5.69 (m, 1 H, 1 H, CH2CHCH2), 5.10 (m, 1 H, CHCH3), 6.02 [d, J ϭ 9.6 Hz, 1
CHϭCHCH2), 5.97 (m, 1 H, CHϭCHCH2) ppm. 13C NMR: δ ϭ
H, C(O)CHϭCH], 6.61Ϫ6.76 [m, 4 H, C(O)CHϭCH, Ph-H] ppm.
21.5 (CHCH3CH3), 23.6 (CCH3CH3), 30.3 (CHϭCHCH2), 30.9 13C NMR: δ ϭ Ϫ4.11 [Si(CH3)2], Ϫ4.07 [Si(CH3)2], 18.4 [C(CH3)3],
[C(O)CH3], 49.3 (CHOCH2), 63.0 [CH(CH3)2], 68.7 (OCHCH2), 20.3 (OCHCH3), 25.9 [C(CH3)3], 29.2 [C(O)CH2CH2], 30.2
92.2 (CHϭCHCH), 126.1 (CHϭCHCH2), 128.1 (CHϭCHCH2), [C(O)CH2], 36.2 (CHϭCHCH2), 40.8 (OCHCH2CHO), 67.1
206.7 (CϭO) ppm. MS: m/z (%) ϭ 198 (1) [Mϩ], 140 (14), 139 (50),
138 (45), 112 (7), 100 (5), 99 (9), 97 (16), 96 (10), 95 (17), 82 (14),
81 (100), 79 (10), 71 (9), 70 (62), 68 (7), 67 (12), 57 (6), 53 (5).
(CH2CHOCH2), 74.9 (OCHCH3), 120.9/121.1/121.2/121.4 [Ph-
Cortho,meta, C(O)CHϭCH], 133.4 (Ph-Cipso), 144.8 [C(O)CHϭCH],
145.2/146.6 (Ph-COSi), 164.0 [C(O)CHϭCH], 172.5 [C(O)CH2]
C11H18O3 (198.26): calcd. C 66.64, H 9.15; found C 66.26, H 9.31. ppm.
These analytical data correspond to those reported.[2d]
Ester 11: -Selectride (1.0  in THF, 1.3 mL, 1.3 mmol) was ad-
ded dropwise at Ϫ100 °C over 30 min to a solution of methyl ke-
tone 4 (100 mg, 0.5 mmol) in THF (170 mL). After the mixture
had been stirred for 4 h at Ϫ78 °C the cooling bath was removed,
and after 30 min the reaction was quenched by addition of water
(50 mL). The usual workup gave a residue, which was filtered
through a pad of silica gel (E). After evaporation of the solvent,
the colourless oil was dissolved in dichloromethane (12 mL), acid
3 (308 mg, 0.8 mmol), DCC (155 mg, 0.8 mmol), and catalytic
amounts of DMAP were added at room temperature, and the sys-
tem was stirred for 2 h. The reaction mixture was diluted with di-
ethyl ether (15 mL), filtered through a pad of Celite, and concen-
trated in vacuo. The crude product was purified by column chroma-
tography (PE/E, 10:1) to give 212 mg (72%, 2 steps) of ester 11 as
a colourless oil. Rf ϭ 0.29 (PE/E, 8:1). [α]2D2 ϭ Ϫ8.7 (c ϭ 1.02,
CHCl3). IR: ν˜ ϭ 2959, 2932, 2894, 2859, 1734, 1511, 1295, 1255,
Tarchonanthuslactone (1): Benzoic acid (13 mg, 0.1 mmol) and
TBAF (1.0  solution in THF, 0.1 mL, 0.1 mmol) were added at
room temperature to a solution of TBS-protected tarchonanthus-
lactone (12, 20 mg, 0.04 mmol) in THF (1.5 mL) and the mixture
was stirred for 2 h. The reaction was quenched by addition of water
(2 mL). The usual workup gave a residue, which was purified by
column chromatography (E) to give 10 mg (87%) of tarchonanthus-
lactone (1) as a colourless solid. Rf ϭ 0.30 (E). [α]2D8 ϭ Ϫ80.8 (c ϭ
0.4, CHCl3). 1H NMR: δ ϭ 1.21 (d, J ϭ 6.0 Hz, 3 H, CHCH3),
1.78 (m, 1 H, CHϭCHCHH), 2.10 (m, 1 H, CHϭCHCHH),
2.15Ϫ2.35 (m, 2 H, CH2CHCH3), 2.62 (t, J ϭ 6.9 Hz, 2 H,
CH2Ph), 2.85 [t, J ϭ 6.9 Hz, 2 H, C(O)CH2], 4.25 (m, 1 H,
CH2CHCH2), 5.08 (m, 1 H, CHCH3), 6.03 [d, J ϭ 10.3 Hz, 1 H,
C(O)CHϭCH], 6.59 [m, 1 H, C(O)CHϭCH], 6.70Ϫ6.86 (m, 3 H,
Ph-H) ppm.
1126, 1018, 908, 841, 783 cmϪ1 1H NMR: δ ϭ 0.17 [s, 6 H,
.
These analytical data correspond to those reported.[2d]
Si(CH3)2], 0.18 [s, 6 H, Si(CH3)2], 0.98 (s, 9 H, tBu), 0.99 (s, 9 H,
tBu), 1.14Ϫ1.26 (m, 9 H, CHCH3CH3, CHCH3CH3, OCHCH3),
1.62 (m, 1 H, CHCHHCH), 1.94 [m, 3 H, CHCHHCH, C(O)CH2],
2.52 (dd, J ϭ 8.9/6.8 Hz, 2 H, CHϭCHCH2), 2.80 [t, J ϭ 7.9 Hz,
2 H, C(O)CH2CH2], 3.99 (m, 2 H, OCHCH3, CH2CHOCH2), 5.08
[m, 2 H, CH(CH3)2, CHCHϭCH], 5.68 (ddd, J ϭ 10.2/5.1/2.2 Hz,
1 H, CHCHϭCH), 5.96 (m, 1 H, CHCHϭCH), 6.61Ϫ6.76 (m, 3
H, Ph-H) ppm. 13C NMR: δ ϭ 4.1 [Si(CH3)2], 18.4 [C(CH3)3], 19.9
(CCH3CH3), 21.7 (CCH3CH3), 23.8 (OCHCH3), 25.9 [C(CH3)3],
30.3 [C(O)CH2CH2], 30.6 [C(O)CH2], 36.4 (CHϭCHCH2),
41.6 (OCHCH2CHO), 63.2 (CH2CHOCH2), 68.0 [CH(CH3)2],
68.9 (OCHCH3), 92.5 (OCHCHϭCH), 120.9/121.1/121.2 (Ph-
Cortho,meta), 126.1 (OCHCHϭCH), 128.4 (OCHCHϭCH), 133.6
(Ph-Cipso), 145.2/146.6 (Ph-COSi), 172.4 (CϭO) ppm. MS: m/z
(%) ϭ 592 (14) [Mϩ], 534 (11), 477 (7), 476 (16), 475 (46), 393 (10),
391 (6), 365 (5), 355 (9), 354 (5), 353 (66), 351 (16), 335 (8), 237
(8), 223 (7), 222 (12), 221 (80), 185 (7), 181 (10), 180 (15), 179 (100),
165 (6), 151 (8), 149 (8), 141 (18), 131 (12), 125 (5), 123 (50), 122
(9), 119 (5), 113 (11), 107 (5), 105 (7), 101 (5), 99 (19), 97 (8), 95
(22), 93 (11), 85 (5), 83 (8), 82 (5), 81 (48), 79 (6), 75 (6), 74 (5), 73
(90), 71 (17), 70 (6), 69 (19), 67 (7), 59 (13), 57 (17), 55 (17), 51 (5),
51 (24), 45 (37). C32H56O6Si2 (592.95): calcd. C 64.82, H 9.52;
found C 64.97, H 9.58.
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 380) and the Fonds der Chemischen Industrie. We thank Dr.
Michael Müller, Forschungszentrum Jülich, for his collaboration in
this project and for providing us with the chloro lactone 5. The
donation of chemicals by BASF AG and Bayer AG is gratefully
acknowledged.
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TBS-Protected Tarchonanthuslactone (12): Freshly ground PCC
(230 mg, 1.0 mmol) was added at room temperature to a solution
of ester 11 (103 mg, 0.2 mmol) in dichloromethane (4 mL) and the
mixture was stirred for 3 h. The brown solid was removed by fil-
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Received July 3, 2003
4454
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4450Ϫ4454