The total synthesis of both enantiomers of the macrocyclic lactone zearalane

Article abstract of DOI:10.1002/1099-0690(200112)2001:24<4701::AID-EJOC4701>3.0.CO;2-6

A straightforward approach to both enantiomers of zearalane is described from the enantiomerically pure alkenol (S)-4, prepared by a kinetic enzymatic resolution of the racemate. The key step is a Pd-catalyzed cross-coupling of an arene trifluoromethanesulfonate with a 9-alkyl-9-borabicyclo-[3.3.1]nonane derivative. The two enantiomers 2a and 2b have been obtained in an enantiodivergent manner by macrolactonization of the hydroxy acid (S)-7 with either Gerlach's modification of the Corey lactonization or a Mitsunobu lactonization.

Full text of DOI:10.1002/1099-0690(200112)2001:24<4701::AID-EJOC4701>3.0.CO;2-6

FULL PAPER
The Total Synthesis of Both Enantiomers of the Macrocyclic Lactone
Zearalane
Franz Bracher*[a] and Jürgen Krauß[a]
Keywords: Macrocycles / Lactones / Hydroboration / Cross-coupling / Zearalane
A straightforward approach to both enantiomers of zearalane
is described from the enantiomerically pure alkenol (S)-4,
prepared by a kinetic enzymatic resolution of the racemate.
[3.3.1]nonane derivative. The two enantiomers 2a and 2b
have been obtained in an enantiodivergent manner by mac-
rolactonization of the hydroxy acid (S)-7 with either Gerlach’s
The key step is a Pd-catalyzed cross-coupling of an arene modification of the Corey lactonization or a Mitsunobu lac-
trifluoromethanesulfonate with
a
9-alkyl-9-borabicyclo-
tonization.
Introduction
both enantiomers of 2. These lactones were prepared from
two building blocks: the enantiopure carbinols (R)- or (S)-
4 and the known arene triflate 3,[8] as shown in the retrosyn-
thetic scheme (Scheme 1).
In 1962 Stob et al. isolated the 14-membered macrocyclic
lactone zearalenone (1) from the fungus Gibberella zeae
(syn.: Fusarium graminearum).[1] This compound showed
interesting estrogenic and anabolic activities. Starting from
this natural product Urry and Wehrmeister[2] prepared a
number of derivatives, which show higher anabolic and es-
trogenic activities. The macrocyclic lactone (S)-zearalane
(2a) was prepared from 1 by hydrogenation of the double
bond and reduction of the ketone to a methylene group.
Compound 2a also showed estrogenic and anabolic activit-
ies, but it also has anthelminthic and immunomodulating
properties.[3]
The chiral carbinols (S)-4 and (R)-4 were synthesized in
two different ways (Scheme 2). The (S)- enantiomer is avail-
able starting from dec-9-en-1-ol. This alcohol was oxidized
under Swern conditions to the known dec-9-enal,[9] which
was reacted with methylmagnesium iodide to give (Ϯ)-un-
dec-10-en-2-ol (4). Racemate 4 was submitted to a kinetic
enzymatic resolution with a lipase from Pseudomonas spe-
cies in the presence of vinyl acetate leading to the acetate
(R)-5 (ee ϭ 60%) and unchanged alcohol (S)-4 (ee Ͼ 98%).
The enantiomeric excess of (S)-4 and (R)-5 was determined
by GLC after derivatization with (R)-phenylethyl isocyan-
ate. The enzyme could be recovered from the reaction mix-
ture by simple filtration and could be used again for the
same reaction without significant loss of activity. (R)-4 is
also a natural product, which can be isolated from the fresh
bark of Litsea elliptica.[10] Since (R)-4 could be obtained
from (R)-5 by alkaline ester hydrolysis only with low enanti-
omeric excess, we developed another synthesis of (R)-4 by
reaction of (R)-propylene oxide with 7-octenylmagnesium
bromide. The product was obtained with high enantiomeric
excess (Ͼ 96%), but only in poor yield.
Results and Discussion
In continuation of our work on polyketide-derived nat-
ural products
[4Ϫ7]
we describe here the total synthesis of
Scheme 2. i. lipase PS, vinyl acetate; ii. (R)-propylene oxide
Scheme 1
[a]
Department of Pharmacy, University of Munich
Butenandtstr. 5Ϫ13, 81377 Munich, Germany
Fax: (internat.) ϩ 49-(0)89/2180-7802
Therefore it appeared reasonable to use readily available
(S)-4 for the preparation of both enantiomers of zearalane
(2) in an enantiodivergent synthesis.
E-mail: Franz.Bracher@cup.uni-muenchen.de
Eur. J. Org. Chem. 2001, 4701Ϫ4704
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1224Ϫ4701 $ 17.50ϩ.50/0
4701

F. Bracher, J. Krauß
FULL PAPER
rotary evaporator under reduced pressure. GLC was performed on
a phenylmethylsilicone stationary phase (AT-50, Alltech) on a Shi-
madzu GC-14 A gas chromatograph equipped with FID.
Thus, the enantiopure hydroxy olefin (S)-4 was reacted
with two equivalents of 9-BBN to give an organoborane
(Scheme 3). In this reaction one equivalent of 9-BBN added
to the double bond to give a terminal B-alkyl-9-BBN deriv-
ative, whereas the second equivalent was consumed by reac-
tion with the carbinol group.[4] The crude organoborane
was employed for a Pd-catalyzed cross-coupling reaction[11]
with the arene triflate 3 to give, after aqueous workup, the
alkylated arene (S)-6. Alkaline ester hydrolysis of (S)-6 gave
the hydroxy acid (S)-7, which was converted into (R)-O,O-
dibenzylzearalane [(R)-8] by lactonization under Mitsunobu
conditions.[12] This reaction occurs with clean inversion at
the chiral centre. Enantiomerically pure (S)-8 was obtained
by lactonization of (S)-7 using Gerlach’s modification of
the Corey conditions[4,13] with complete retention at the
chiral centre. Debenzylation of (R)-8 and (S)-8 by catalytic
hydrogenation gave pure (R)-zearalane (2b) and (S)-zearal-
ane (2a).
(؎)-Undec-10-en-2-ol (4): A solution of methylmagnesium iodide
(5.0 mmol) in diethyl ether (4 mL) was added during 30 min to a
stirred solution of dec-9-enal[9] (0.46 g, 3.0 mmol) in 2 mL diethyl
ether. The mixture was stirred for 30 min and then poured into 10
mL of a saturated solution of ammonium chloride. The aqueous
layer was extracted with diethyl ether (2 ϫ 10 mL) and after evap-
oration of the organic layer the residue was purified by flash col-
umn chromatography (hexane/ethyl acetate, 5:1) to give 430 mg
(80%) of 4 as a colourless oil. C11H22O (170.29): calcd. C 77.59, H
1
13.01; found C 77.03, H 13.54. H NMR (CD3COCD3): δ ϭ 1.17
(d, J ϭ 6.4 Hz, 3 H, CH3), 1.18Ϫ1.58 (m, 12 H, 6 CH2), 1.96 (s, 3
H, CH3), 2.05 (m, 2 H, CH2), 4.83 (tq, J ϭ 6.4, J ϭ 7.0, 1 H, CH),
4.91 (m, 1 H, HCϭ), 4.98 (ddt, J ϭ 1.7, J ϭ 17.2, J ϭ 2.1, 1 H,
H2Cϭ), 5.80 (ddt, J ϭ 6.7, J ϭ 10.1 Hz, J ϭ 17.2 Hz, 1 H, -CHϭ).
13C NMR (CD3COCD3): δ ϭ 20.2 (CH3), 21.1 (CH3), 26.1
(CH2), 29.6 (CH2), 29.7 (CH2), 30.0 (CH2), 30.1 (CH2), 30.4 (CH2),
36.6 (CH2), 71.0 (C-2), 114.6 (CH2ϭ), 139.8 (ϪCHϭ), 170.5
(COO). IR (film): ν ϭ 2958 cmϪ1, 2929, 2858, 1735, 1462, 1373,
˜
1272, 1248, 1125, 1072, 743. MS (70 eV): m/z (%) ϭ 197 (0.8) [Mϩ
Ϫ 15], 152 (10), 124 (19), 110 (22), 82 (38), 43 (100).
Kinetic Enzymatic Resolution of Racemate 4: (Ϯ)-Undec-10-en-2-ol
(4; 0.20 g, 1.2 mmol) was dissolved in tert-butyl methyl ether (3
mL), and lipase PS (Amano; 100 mg) and vinyl acetate (0.50 g,
6.0 mmol) were added. The suspension was stirred for 2 days at
room temperature. It was then filtered and the organic solvent was
evaporated. The residue was purified by flash column chromato-
graphy (ethyl acetate/hexane, 1:5) to give 89 mg (35%) of (R)-5 and
80 mg (40%) of (S)-4 as colourless liquids.
(R)-Undec-10-en-2-yl Acetate [(R)-5]: C13H24O2 (212.33): calcd. C
1
73.54, H 11.39; found C 73.55, H 11.40. H NMR ([D6]acetone):
δ ϭ 1.17 (d, J ϭ 6.4 Hz, 3 H, CH3), 1.18Ϫ1.58 (m, 12 H, 6 CH2),
1.96 (s, 3 H, CH3), 2.05 (m, 2 H, CH2), 4.83 (tq, J ϭ 6.4, J ϭ 7.0,
1 H, CH), 4.91 (m, 1 H, -CHϭ), 4.98 (ddt, J ϭ 1.7, J ϭ 17.2, J ϭ
2.1, 1 H, H2Cϭ), 5.80 (ddt, J ϭ 6.7, J ϭ 10.1 Hz, J ϭ 17.2 Hz, 1
H, -CHϭ). 13C NMR ([D6]acetone): δ ϭ 20.2 (CH3), 21.1 (CH3),
26.1 (CH2), 29.6 (CH2), 29.7 (CH2), 30.0 (CH2), 30.0 (CH2), 30.4
(CH2), 36.6 (CH2), 71.0 (C-2), 114.6 (CH2ϭ), 139.8 (ϪCHϭ), 170.5
(CO). IR (film): ν ϭ2958 cmϪ1, 2929, 2858, 1735, 1462, 1373, 1272,
˜
1248, 1125, 1072, 743. MS (70 eV): m/z (%) ϭ 197 (0.8) [Mϩ Ϫ 15],
152 (10), 124 (22), 82 (38), 43 (100). [α]2D5 ϭ Ϫ0.975 (c ϭ 5.129,
CHCl3). ee ϭ 60% (GLC after alkaline hydrolysis and derivatiz-
ation with (R)-phenylethyl isocyanate).
Scheme 3. i. 2 equiv. 9-BBN, Pd(PPh3)4, K3PO4; ii. 4  KOH; iii.
(PyS)2, PPh3, AgClO4; iv. PPh3, DEAD; v. H2/Pd (C)
(S)-Undec-10-en-2-ol [(S)-4]: The spectroscopic data of (S)-4 were
in full agreement with those of 4; [α]2D5 ϭ ϩ 6.62 (c ϭ 0.455,
CHCl3). ee Ͼ 98% (GLC after derivatization with (R)-phenylethyl
isocyanate).
Experimental Section
General: Elemental analyses were performed on a Carlo Erba
CHNO Elemental Analyser. FTIR spectra were recorded on a Pye-
Unicam PU-9800 spectrometer. NMR spectra were recorded in
CDCl3 with tetramethylsilane as internal standard on a Bruker
AM-400 (1H: 400.1 MHz; 13C: 100.5 Hz ) spectrometer. J values
are given in Hz. Mass spectra were recorded on a Finnigan MAT-
(R)-Undec-10-en-2-ol [(R)-4]: A solution of oct-7-enylmagnesium
bromide (8.0 mmol) in THF (3 mL) was added at Ϫ70 °C to a
stirred suspension of CuBr·S(CH3)2 (1.6 g, 7.4 mmol) in 5 mL THF
and the mixture was allowed to warm to Ϫ10 °C. After cooling to
Ϫ70 °C a solution of (R)-propylene oxide (0.46 g, 3.0 mmol) in
THF (2 mL) was added. After 12 h the reaction was quenched with
saturated ammonium chloride solution (10 mL) and extracted with
diethyl ether (3 ϫ 10 mL). The organic layer was purified as de-
scribed above.
8430 spectrometer. Optical rotations were recorded on
a
PerkinϪElmer 241 polarimeter, and are given in units of 10Ϫ1 deg
cm2 gϪ1. Flash column chromatography was carried out on Merck
Kieselgel 60 (230Ϫ400 mesh). Tetrahydrofuran (THF) was freshly
distilled from sodium benzophenone ketyl prior to use. The organic
The spectroscopic data of (R)-4 were in full agreement with those
extracts were dried over anhydrous sodium sulfate which was later of 4; [α]2D5 ϭ Ϫ6.85 (c ϭ 0.16, CHCl3). ee Ͼ 96% (GLC after deriva-
removed by filtration. The solvent used was concentrated using a
4702
tization with (R)-phenylethyl isocyanate).
Eur. J. Org. Chem. 2001, 4701Ϫ4704

The Total Synthesis of Both Enantiomers of the Macrocyclic Lactone Zearalane
(S)-Methyl 2,4-Dibenzyloxy-6-(10-hydroxyundecyl)benzoate [(S)-6]: 1.28Ϫ1.75 (m, 16 H, 8 CH2), 2.30Ϫ2.77 (m, 2 H, CH2), 4.99 (d,
FULL PAPER
An oven-dried flask equipped with a reflux condenser and a sep-
tum inlet was flushed with N2, charged with a solution of 9-BBN
J ϭ 6.2 Hz, 2 H, CH2O), 5.03 (s, 2 H, CH2O), 5.22 (tq, J ϭ 6.2,
J ϭ 6.0, 1 H, CH), 6.44 (d, J ϭ 2.1 Hz, 1 H, aromat. CH), 6.47
(0.5  in THF; 4.8 mL, 2.4 mmol) and then the alkenol (S)-4 (d, J ϭ 2.1 Hz, 1 H, aromat. CH), 7.28Ϫ7.42 (m, 10 H,
(0.20 g, 1.2 mmol) was added at 0 °C. The mixture was warmed
slowly to room temperature and stirred for 4Ϫ6 h to give a solution
of the alkyl-9-BBN derivative. Dioxane (4 mL), water (5 mL), pow-
aromat.CH). 13C NMR (CDCl3): δ ϭ 20.0 (CH3), 21.9 (CH2), 24.2
(CH2), 25.1 (CH2), 25.6 (CH2), 26.0 (CH2), 27.2 (CH2), 29.8 (CH2),
32.4 (CH2), 35.0 (CH2), 70.1 (CH2O), 70.5 (CH2O), 70.7 (HCOH),
dered K3PO4 (0.37 g, 1.7 mmol), Pd(PPh3)4 (134 mg, 0.11 mol) and 98.1 (aromat. CH), 106.8 (aromat. CH), 117.8 (quat. C), 126.9
arene triflate 3 (595 mg, 1.2 mmol) were then added to this solu-
tion. The mixture was heated at 95 °C for 16 h, then extracted with
(quat. C), 127.5 (aromat. CH), 127.6 (aromat. CH), 127.9 (aromat.
CH), 128.1 (aromat. CH), 128.4 (aromat. CH), 128.6 (aromat. CH),
diethyl ether and the organic layer was evaporated. The residue was 136.7 (quat. C), 142.8 (quat. C), 156.9 (quat. C), 160.2 (quat. C),
168.5 (COO). IR (film): ν ϭ 2928 cmϪ1, 2859, 1717, 1606, 1579,
˜
separated by flash column chromatography (hexane/ethyl acetate
5:1) to give 330 mg (53%) of (S)-6 as a colourless oil. C33H42O5·
1498, 1380, 1322, 1164, 758, 701, 661. MS (70 eV): m/z (%) ϭ 486
1/2H2O (527.70): calcd. C 75.16, H 8.15; found C 75.05, H 8.54. (6) [Mϩ], 279 (19), 167 (46), 149 (100), 91 (68). [α]2D5 ϭ Ϫ54.25 (c ϭ
1H NMR (CDCl3): δ ϭ 1.18 (d, J ϭ 6.3 Hz, 3 H, CH3), 1.25Ϫ1.63 0.153, CHCl3).
(m, 16 H, 8 CH2), 2.55 (dd, J ϭ 7.7, J ϭ 8.0, 2 H, CH2), 3.77 (m,
(S)-O,O-Dibenzylzearalane [(S)-8]: Hydroxy acid (S)-7 (100 mg,
0.20 mmol), di(2-pyridyl)disulfide (60 mg, 0.26 mmol) and PPh3
(68 mg, 0.26 mmol) were dissolved in anhydrous acetonitrile (10
mL). This solution was stirred at room temperature for 1 h and
then added dropwise over 2 h to a refluxing solution of anhydrous
silver perchlorate (188 mg, 0.9 mmol) in anhydrous acetonitrile
(100 mL). After complete addition the mixture was refluxed for a
further 30 min and then cooled to room temperature and the solv-
ents evaporated. The residue was partitioned between a solution of
sodium cyanide (1 g) in water (30 mL) and ethyl acetate (3 ϫ 30
mL) followed by flash column chromatography (hexane/ethyl acet-
ate, 20:1) to give 29 mg (30%) of (S)-8 as a viscous yellow oil.
1 H, CH), 3.85 (s, 3 H, OCH3), 5.02 (s, 2 H, OCH2), 5.04 (s, 2 H,
OCH2), 6.43 (s, 2 H, aromat. CH), 7.30Ϫ7.39 (m, 10 H, aromat.
CH). 13C NMR (CDCl3): δ ϭ 23.5 (CH3), 25.8 (CH2), 29.4 (CH2),
29.5 (CH2), 29.6 (CH2), 29.6 (CH2), 31.1 (CH2), 33.9 (CH2), 39.4
(CH2), 52.0 (OCH3), 68.2 (CHOH), 70.1 (OCH2), 70.4 (OCH2),
98.4 (aromat. CH), 107.3 (aromat. CH), 117.0 (quat. C),
126.9Ϫ128.6 (m, aromat. CH), 136.6 (quat. C), 136.8 (quat. C),
143.17 (quat. C), 157.1 (quat. C), 160.4 (quat. C), 168.8 (COOH).
IR (film): ν˜ ϭ 2926 cmϪ1, 2854, 1727, 1603, 1585, 1432, 1326, 1267,
1160, 736; 697. MS (70 eV): m/z (%) ϭ 518 (12) [Mϩ]; 395 (12),
272 (10), 181 (14), 91 (100). [α]2D5 ϭ 2.60 (c ϭ 0.96, CHCl3).
(S)-2,4-Dibenzyloxy-6-(10-hydroxyundecyl)benzoic Acid [(S)-7]:
Methyl ester (S)-6 (0.3 g, 0.6 mmol) was dissolved in ethanol (5
mL) and 4  KOH (5 mL). The solution was refluxed for 30 h,
extracted with 10 mL diethyl ether and the aqueous layer was acidi-
fied with 4  HCl (10 mL). The solution was then extracted with
diethyl ether (3 ϫ 10 mL). The organic layer was evaporated to
give 120 mg (49%) of (S)-7 as a yellow oil. C32H40O5·2H2O
The spectroscopic data for (S)-8 were in full accordance with those
of (R)-8; [α]2D5 ϭ 50.96 (c ϭ 5.0, CHCl3).
(R)-Zearalane (2b): (R)-O,O-dibenylzearalane [(R)-8] (0.10 g,
0.20 mmol) was dissolved under N2 in 1 mL ethyl acetate and 10
mL methanol, Pd /C (10%; 20 mg) was then added and the mixture
was hydrogenated for 4 h. After filtration the organic solvents were
evaporated and the residue separated by flash column chromato-
graphy (hexane/ethyl acetate, 40:3) to give 50 mg (79%) of 2b as
white crystals, m.p.: 157 °C. C18H26O4 (486.65): calcd. C 70.57, H
8.55; found C 70.25, H 8.41. 1H NMR (CDCl3): δ ϭ 1.23Ϫ1.65
(m, 10 H, 5 CH2), 1.36 (d, J ϭ 6.1 Hz, 3 H, CH3), 1.70Ϫ1.92 (m,
2 H, CH2), 2.42 (dt, J ϭ 4.4, J ϭ 12.5 Hz, 1 H, CH2), 3.26 (dt,
J ϭ 4.4, J ϭ 12.3 Hz, 1 H, CH), 5.19 (dtq, J ϭ 1.1, J ϭ 4.4, J ϭ
6.1 Hz, 1 H, CH), 5.74 (s, 1 H, OH), 6.24 (d, J ϭ 2.7 Hz, 1 H,
aromat. CH), 6.29 (d, J ϭ 2.7 Hz, 1 H, aromat. CH), 12.23 (s, 1
H, OH). 13C NMR (CDCl3): δ ϭ 21.3 (CH3), 22.5 (CH2), 22.5
(CH2), 22.7 (CH2), 26.7 (CH2), 26.8 (CH2), 26.8 (CH2), 31.3 (CH2),
34.8 (CH2), 37.2 (CH2), 73.7 (CH), 101.5 (aromat. CH), 105.4
(quat. C), 110.6 (aromat. CH), 149.2 (quat. C), 160.3 (quat. C),
1
(540.70): calcd. C 71.08 H 8.20; found C 69.43 H 8.37. H NMR
(CDCl3): δ ϭ 1.18 (d, J ϭ 6.2 Hz, 3 H, CH3,), 1.21Ϫ1.38 (m, 12
H, 6 CH2), 1.59 (m, 2 H, CH2), 2.79 (m, 2 H, CH2), 3.82 (m, 1 H,
CH), 5.03 (s, 2 H, CH2), 5.09 (s, 2 H, CH2), 6.46 (d, J ϭ 2.2 Hz, 1
H, aromat. CH), 6.47 (d, J ϭ 2.2 Hz, 1 H, aromat. CH), 7.25Ϫ7.40
(m, 10 H, aromat.CH). 13C NMR (CDCl3): δ ϭ 23.4 (CH3), 25.5
(CH2), 29.0 (CH2), 29.3 (CH2), 29.3 (CH2), 29.4 (CH2), 31.2 (CH2),
34.7 (CH2), 68.4 (CHOH), 70.1 (CH2O), 71.3 (CH2O), 98.6
(aromat. CH), 108.8 (aromat. CH), 127.2 (aromat. CH), 127.6
(aromat. CH), 128.1 (aromat. CH), 128.2 (aromat. CH), 128.6
(aromat. CH), 128.7 (aromat. CH), 135.8 (quat. C), 136.3 (quat. C),
146.7 (quat. C), 161.0 (quat. C), 158.0 (quat. C), 168.9 (COOH). IR
(film): ν ϭ 2927 cmϪ1, 2854, 2360, 1706, 1602, 1286, 1163. MS
˜
(70 eV): m/z (%) ϭ 504 (0.6) [Mϩ], 460 (3), 214 (6), 91 (100). [α]2D5
2.45 (c ϭ 1.13, CHCl3).
ϭ
165.6 (quat. C), 171.8 (COO). IR (KBr): ν ϭ 3391 cmϪ1, 2946,
˜
2922, 2870, 2853, 1639, 1585, 1257, 1177, 1098, 1020, 839. MS
(70 eV): m/z (%) ϭ 306 (40) [Mϩ], 288 (20), 168 (100). [α]2D5
Ϫ30.84 (c ϭ 0.32, CHCl3).
ϭ
(R)-O,O-Dibenzylzearalane [(R)-8]: PPh3 (0.70 g, 2.5 mmol) was dis-
solved under N2 in 290 mL toluene. DEAD (0.4 mL, 2.6 mmol)
was added to the solution and stirred for 20 min. Over a period of
6 h half of a solution of the hydroxy acid (S)-7 (240 mg, 0.5 mmol)
in THF (1.5 mL) and toluene (3.7 mL) was added very slowly with
a syringe pump. After stirring for 10 h more PPh3 (0.35 g,
1.3 mmol) and DEAD (0.2 mL, 1.3 mmol) were added and the rest
of the solution of the hydroxy acid was then added over 6 h. After
stirring for 10 h the organic solvent was evaporated and the residue
was separated by flash column chromatography (hexane/ethyl acet-
ate, 20:1) to give 120 mg (49%) of (R)-8 as a white solid, m.p.: 96
(S)-Zearalane (2a): This compound was prepared from (S)-8 under
the conditions described for 2b. The spectroscopic data for 2a were
in full agreement with those of 2b; [α]2D5 ϭ 36.8 (c ϭ 1.0, CHCl3).
White crystals, m.p.: 154 °C (ref.:[3] 154 Ϫ156 °C).
Acknowledgments
°C. C32H38O4 (486.65): calcd. C 78.98, H 7.86; found C 77.95, H We thank the Fonds der Chemischen Industrie for financial sup-
8.35. 1H NMR (CDCl3): δ ϭ 1.11 (d, J ϭ 6.2 Hz, 3 H, CH3),
port and Amano for a gift of Pseudomonas lipase.
Eur. J. Org. Chem. 2001, 4701Ϫ4704
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F. Bracher, J. Krauß
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4704
Eur. J. Org. Chem. 2001, 4701Ϫ4704