Chemo-enzymatic enantio-convergent asymmetric total synthesis of (S)-(+)-dictyoprolene using a kinetic resolution - Stereoinversion protocol

Article abstract of DOI:10.1016/S0957-4166(03)00481-6

A single enantiomer of a (stereo)chemically labile allylic-homoallylic alcohol was obtained in 91% e.e. and 96% yield from the racemate by employing a lipase-catalysed kinetic resolution coupled to in situ inversion under carefully controlled (Mitsunobu) conditions in order to suppress side reactions, such as elimination and racemisation. This technique was successfully applied to an enantio-convergent asymmetric total synthesis of the algal fragrance component (S)-dictyoprolene.

Full text of DOI:10.1016/S0957-4166(03)00481-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2427–2432
Chemo-enzymatic enantio-convergent asymmetric total synthesis
of (S)-(+)-dictyoprolene using a kinetic
resolution—stereoinversion protocol
Andreas Wallner, Harald Mang, Silvia M. Glueck, Andreas Steinreiber, Sandra F. Mayer and
Kurt Faber*
Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria
Received 23 May 2003; accepted 12 June 2003
Abstract—A single enantiomer of a (stereo)chemically labile allylic-homoallylic alcohol was obtained in 91% e.e. and 96% yield
from the racemate by employing a lipase-catalysed kinetic resolution coupled to in situ inversion under carefully controlled
(Mitsunobu) conditions in order to suppress side reactions, such as elimination and racemisation. This technique was successfully
applied to an enantio-convergent asymmetric total synthesis of the algal fragrance component (S)-dictyoprolene.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Our synthetic strategy was based on the racemic sec-
ondary alcohol rac-6 (Scheme 2). We envisaged that the
latter (or its corresponding acetate 1) would be an ideal
candidate for enantioseparation employing lipase-tech-
nology via acyl-transfer or ester hydrolysis, respec-
tively.6,5 Due to the apparent symmetry of ester
hydrolysis versus acyl-transfer, the stereochemical out-
come can be controlled towards the desired enantiomer
by choosing the forward- and reverse-reaction mode.7
Brown algae belonging to the genus Dictyopteris prolif-
era and D. membranacea are known to possess charac-
teristic odors.1,2 A component thereof resembling the
scent of ‘beach’ is the doubly unsaturated sec-acetate
ester (S)-dictyoprolene (S)-1 (Scheme 1), isolated in
1979.3 Besides its odoriferous properties, it represents a
key intermediate in the biosynthesis of many C11 hydro-
carbons from Dictyopteris prolifera.4 Its structure and
absolute configuration were determined by NMR and
MS spectroscopy and independent synthesis in non-
racemic form.4 Herein, we describe a concise synthesis
of (S)-dictyoprolene (S)-1 using a chemo-enzymatic
approach.5 High synthetic efficiency is ensured by
avoiding the occurrence of ‘unwanted’ stereoisomers via
enantio-convergent transformations.
The most striking limitation of kinetic resolution is the
maximum theoretical yield of 50% of each enantiomer.
In order to circumvent this drawback, several
approaches have been developed, which render an
enantio-convergent process delivering a single enan-
tiomeric product in 100% theoretical yield.8 The most
widely employed techniques are.
(i) Dynamic kinetic resolution implies in situ racemiza-
tion of the starting material during kinetic resolution.
The latter is achieved by using bio-9–11 or chemo-cata-
lysts,12–14 which are often based on transition metals,
such as Ru.15,16
(ii) Selective inversion of one enantiomer (in presence of
the other) via a chemo-enzymatic protocol renders a
single enantiomer.17,18
Scheme 1. Dictyoprolene (S)-1.
Since the allylic alcohol moiety in compound 6 is
* Corresponding author. Tel.: +43-316-380-5332; fax: +43-316-380-
9840; e-mail: kurt.faber@uni-graz.at
incompatible with Ru-complexes,19 in situ racemization
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00481-6

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A. Wallner et al. / Tetrahedron: Asymmetry 14 (2003) 2427–2432
Scheme 2. Synthesis of rac-substrates.
of the latter failed and dynamic resolution was inappli-
cable. As a consequence, the system of choice was
based on stereo-inversion.17,18 Thus, kinetic resolution
furnishes an enantiomeric pair of alcohol 6 and the
corresponding ester 1. In order to obtain both com-
pounds at a maximum of enantiomeric excess, the point
of conversion—which is close to or slightly beyond
50%, depending on the enantioselectivity—has to be
carefully chosen.20,21 Without separation of the mixture
of enantiomeric ester and alcohol, the latter is con-
verted into an activated derivative bearing a good
leaving group (i.e. mesylate,22 sulfate,23 triflate,
nitrate,24 borate,24 etc.). This enantiomeric product
mixture consisting of an activated and a non-activated
sec-alcohol derivative can be (chemically) hydrolyzed
through opposite stereochemical pathways: Whereas
the carboxylate ester is hydrolyzed with retention of
configuration, the activated enantiomeric derivative
undergoes inversion, which furnishes the same enan-
tiomeric sec-alcohol as the sole product in 100% theo-
retical yield. This so-called ‘in situ inversion’-technique
has been successfully employed to chemically rather
stable sec-alcohols.
aldehyde, which was trapped in situ with vinyl magne-
sium bromide at room temperature to furnish alcohol
rac-6 in 47% yield. In order to avoid isomerization of
the configurationally labile E-double bond, all of the
former reactions had to be performed at low tempera-
ture. Acetylation of rac-6 gave acetate rac-1 according
to literature procedures.26
Substrate rac-6 was screened with several lipases (from
Geotrichum candidum, Rhizomucor miehei, Candida
antarctica and Pseudomonas sp.) for transesterification
in hexane at room temperature using vinyl acetate as an
acyl donor (Scheme 3). Table 1 shows the stereoselec-
tivities denoted as the enantiomeric ratio (E)27 obtained
in the kinetic resolution of rac-6 using various lipases.
All reaction rates were in a reasonable range except
lipase from R. miehei (Novo SP 524), which showed no
conversion. Invariably, all fungal and bacterial lipases
exhibited (S)-preference. In general, rac-6 was con-
verted with disappointingly low enantioselectivities,
only Lipase Amano PS gave (S)-1 in an e.e. up to 98%
(E >200).5 These results clearly demonstrate that—
depending on the substrate—enantioselectivities of
lipases often vary to a great extent, even for lipases
from a closely related microbial source: Lipase prepara-
tions AH, AK, PS, PS-C and SAM-II are all derived
from Pseudomonas sp.
Taking the delicate chemical structure of the allylic-
homoallylic alcohol rac-6 into account, ‘clean’ inver-
sion is not straightforward and several side reactions,
such as racemisation and—most important—elimina-
tion forming a triply unsaturated conjugated system
have to be expected. As a consequence, the use of
triflate, mesylate or nitrate esters was avoided and
Mitsunobu conditions were chosen.25
For preparative-scale biotransformations Lipase
Amano PS was used (Scheme 3). Thus, resolution of
rac-6 was terminated at 51% conversion to furnish
(S)-1 and (R)-6 in 91% e.e. (E ca. 70). Without separa-
tion of products, this mixture was subjected to Mit-
sunobu inversion to give naturally occurring
(S)-dictyoprolene (S)-1 in 91% e.e. as the sole product
in 96% yield. In order to prove the absence of racemisa-
tion during stereoinversion, (S)-1 was hydrolysed under
carefully controlled conditions (K2CO3 at 0°C in
MeOH) to furnish (S)-6 in 90% e.e. In order to provide
access to the mirror-image enantiomers, kinetic resolu-
tion in the ‘reverse direction’ via ester hydrolysis of
rac-1 was performed. In this case, the enantioselectivity
of lipase PS was considerably lower (E 14), although
the same enzyme was used. Absolute configurations of
2. Results and discussion
Substrates alcohol rac-6 or acetate rac-1 for the lipase
catalysed resolution were synthesized via the following
sequence (Scheme 2). Coupling of the Li-anion of 1-
heptyne 2 with bromoacetaldehyde diethylacetal 3 gave
alkyne 4 in 68% yield. The latter was selectively hydro-
genated with Lindlar-catalyst to give the corresponding
cis-alkene 5 in 83% yield. In order to achieve absolute
cis-selectivity, poisoning of the Lindlar catalyst with
quinoline was required. Deprotection of acetal 5
(HCOOH at −40°C in pentane) gave the corresponding
dictyoprolene
1
and 1,5-undecadien-3-ol
6
were
deduced from specific rotation values for (S)-1.4

A. Wallner et al. / Tetrahedron: Asymmetry 14 (2003) 2427–2432
2429
Scheme 3. Biocatalytic synthesis of both enantiomers of dictyoprolene 1 involving lipase-catalysed resolution combined with in
situ (Mitsunobu) inversion.
Table 1. Screening for the kinetic resolution of alcohol rac-6
a
Entry
Lipase
Conversion (%)
Time (h)
E.e.S (%)
E.e.P (%)
Eb
1
2
3
4
5
6
7
8
9
Amano GC-4
Amano GC-20
Candida antarctica A
Candida antarctica B
Amano PS-C
Amano AH
Amano AK
SAM-II
Amano PS
15
36
37
35
42
31
40
34
41
2
1
1
30
1
16
4
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
25 (S)
26 (S)
25 (S)
37 (S)
15 (S)
43 (S)
65 (S)
78 (S)
98 (S)
1.74
2.0
1.9
2.6
1.5
3.0
7.15
12
>200
4
7
n.d.
78 (R)c
a E.e. values of alcohol 6 were not determined in the screening since no direct chiral separation method for alcohol rac-6 could be developed.
b Calculated from e.e.P and c.
c Alcohol 6 was separated from 1 via column chromatography and analyzed as acetate 1. n.d. not determined.
3. Conclusion
(13C)], coupling constants (J) are given in Hz. TLC
plates were run on silica gel Merck 60 (F254) and
compounds were visualized by spraying with Mo-
In summary, we have demonstrated that the combina-
tion of lipase-catalysed kinetic resolution coupled to in
situ inversion is applicable to (stereo)chemically labile
allylic-homoallylic sec-alcohols under carefully con-
trolled (Mitsunobu) reaction conditions to avoid side
reactions. The validity of this protocol was demon-
strated by the enantio-convergent asymmetric total syn-
thesis of (S)-dictyoprolene (S)-1, an algal fragrance
component.
reagent
[(NH4)6Mo7O24·4H2O
(100
g/L),
Ce(SO4)2·4H2O (4 g/L) in H2SO4 (10%)] or by dipping
into a KMnO4 reagent [2.5 g/L KMnO4 in H2O].
Compounds were purified either by flash chromatogra-
phy on silica gel Merck 60 (230–400 mesh) or, for
volatile substances, by Kugelrohr distillation.
Petroleum ether (pet. ether.) had a boiling range of
60–90°C. GC analyses were carried out on a Varian
3800 gas chromatograph equipped with FID and either
an HP1301 capillary column (both 30 m, 0.25 mm, 0.25
mm film, N2). Enantiomeric purities were analyzed using
4. Experimental
a
CP-Chirasil-DEX CB column (‘column A’,
4.1. General remarks
Chrompack, 25 m, 0.32 mm, 0.25 mm film). H2 was
used as a carrier gas. For programs and retention times
vide infra. Optical rotation values were measured on a
Perkin–Elmer polarimeter 341 at 589 nm (Na-line) in a
1 dm cuvette and specific rotations are given in units of
10−1 deg cm2 g−1. Solvents were dried and freshly
distilled by common practice. For anhydrous reactions,
NMR spectra were recorded in CDCl3 using a Bruker
AMX 360 at 360 (1H) and 90 (13C) MHz and a Bruker
DMX Avance 500 at 500 (1H) and 125 (13C) MHz.
Chemical shifts are reported relative to TMS (l 0.00)
with CHCl3 as internal standard [l 7.23 (1H) and 76.90

2430
A. Wallner et al. / Tetrahedron: Asymmetry 14 (2003) 2427–2432
flasks were dried at 150°C and flushed with dry argon
just before use. Organic extracts were dried over
Na2SO4, and then the solvent was evaporated under
reduced pressure. Compounds 2 and 3 were purchased
from Aldrich. All lipases used were commercially avail-
able: Amano Enzyme Inc., Nagoya, Japan (GC-4, GC-
20, PS-C, AH, AK, PS); Novozymes, Bagsvaerd,
Denmark (Candida antarctica A, B); Aldrich (SAM-II).
pentane (3×50 mL). The combined organic phases were
concentrated in vacuo. The residue was dissolved in
anhydrous Et2O (100 mL) under argon and vinylmag-
nesium bromide (100 mL of a 0.5 M solution in Et2O,
50 mmol) was added dropwise at rt. After 30 min the
reaction was quenched with water (150 mL) and Et2O
(200 mL). The phases were separated and the aqueous
layer was extracted with Et2O (2×200 mL). The com-
bined organic phases were dried and evaporated. The
residue was purified by flash chromatography (pet.
4.2. Syntheses of substrates and biocatalytic
transformations
1
ether/EtOAc, 30:1) to afford rac-6 (2.54 g, 47%). H
NMR (500.13 MHz, CDCl3): l=0.86 (3H, t, J=5.8),
1.27–1.37 (6H, m), 1.99–2.05 (2H, m), 2.14 (1H, s),
2.26–2.32 (2H, m), 4.10 (1H, s), 5.07 (1H, dd, J1=9.2,
J2=1.2), 5.21 (1H, dd, J1=15.6, J2=1.3), 5.36 (1H, dt,
J1=9.6, J2=1.2), 5.53 (1H, dt, J1=9.6, J2=1.2), 5.86
(1H, m). 13C NMR (125 MHz, CDCl3): l=14.1, 22.6,
27.4, 29.3, 31.5, 35.1, 72.5, 114.6, 124.4, 133.4, 140.6.
Spectroscopic data were in full agreement with those
previously reported.4
4.2.1. 1,1-Diethoxy-3-nonyne 4. To a stirred solution of
1-heptyne 2 (12.0 g, 125 mmol) under argon in anhy-
drous THF (60 mL), n-BuLi (60 mL of a 2.5 M
solution in hexane, 150 mmol) was added at −78°C.
After 15 min, bromoacetaldehyde diethylacetal 3 (29.5
g, 150 mmol) was added dropwise at −78°C. When the
reaction mixture reached rt HMPA (30 mL) was added
and stirring was continued for 2 h reflux. The reaction
was quenched by addition of H2O (120 mL) and Et2O
(120 mL). The phases were separated and the aqueous
layer was extracted with Et2O (2×80 mL). The com-
bined organic phases were dried and evaporated. The
residue was purified by flash chromatography (pet.
ether/EtOAc, 20:1) to afford 1,1-diethoxy-3-nonyne 4
4.2.4. rac-Dictyoprolene rac-1. To a stirred solution of
alcohol rac-6 (0.3 g, 1.8 mmol) in CH2Cl2, Ac2O (0.24
g, 2.4 mmol), NEt3 (0.26 g, 2.6 mmol) and DMAP (20
mg, cat.) were added. The resulting solution was stirred
at 50°C for 20 h. After the reaction was complete it was
quenched by addition of water (15 mL). After phase
separation the organic phase was dried and concen-
trated. The residue was purified by flash chromatogra-
phy (pet. ether/EtOAc, 25:1) to give rac-1 (0.24 g, 63%)
1
(18.0 g, 63%) as a colourless liquid. H NMR (360.13
MHz, CDCl3): l=0.88 (3H, t, J=7.0), 1.20–1.28 (6H,
dd, J1=7.6, J2=7.0), 1.31–1.35 (4H, m), 1.46–1.48 (2H,
m), 2.13–2.17 (2H, m), 2.47–2.50 (2H, m), 3.53–3.61
(2H, m), 3.66–3.72 (2H, m), 4.61 (1H, t, J=5.7). 13C
NMR (90 MHz, CDCl3): l=14.0, 15.3, 18.8, 22.3, 25.1,
28.7, 31.1, 61.8, 75.2, 82.0, 101.4. Spectroscopic data
were in full agreement with those previously reported.28
1
as a colourless liquid. H NMR (360.13 MHz, CDCl3):
l=0.87 (3H, t, J=6.5), 1.26–1.36 (6H, m), 1.99–2.05
(5H, m), 2.32–2.41 (2H, m), 5.16 (1H, dd, J1=10.5,
J2=1.8), 5.23 (1H, dd, J1=9.6, J2=1.3), 5.27–5.28 (1H,
m), 5.30–5.33 (1H, m), 5.48–5.49 (1H, m), 5.75–5.80
(1H, m). 13C NMR (90 MHz, CDCl3): l=14.1, 21.2,
22.6, 27.4, 29.3, 31.5, 32.2, 74.3, 116.7, 123.5, 133.2,
136.0, 170.3. Spectroscopic data were in full agreement
with those previously reported.4
4.2.2. 1,1-Diethoxy-3(Z)-nonenal (Z)-5. To a solution of
alkyne 4 (15 g, 72.0 mmol) in EtOH (150 mL), quino-
line (4 mL) and Lindlar catalyst (3.5 g) were added and
the resulting mixture was vigorously stirred under H2
for 2 h at atmospheric pressure. Then the solids were
removed by filtration through a plug of Celite-545 and
the solvent was evaporated. Flash chromatography
(pentane/EtOAc, 40:1) afforded pure (Z)-alkene (Z)-5
4.2.5. (S)-1,5-Undecadien-3-ol (S)-6 via biocatalytic in
situ inversion. Lipase Amano PS (1.5 g) was dispersed in
hexane (60 mL), and after addition of rac-6 (1.0 g, 6.1
mmol) and vinyl acetate (2.0 g, 23.2 mmol) the mixture
was agitated on an orbit shaker (rt, 120 rpm). The
reaction was monitored by GC on a chiral stationary
phase. When the conversion had reached 51% (8 h), the
biocatalyst was filtered off and the solution was concen-
trated in vacuo. The residue was dissolved in anhydrous
THF (100 mL), and AcOH (7.2 g, 120 mmol) and PPh3
(31.4 g, 120 mmol) were added. The reaction mixture
was immediately cooled to −40°C and a solution of
diisopropyl azodicarboxylate (24.0 g, 120 mmol) in
anhydrous THF (25 mL) was added. The solution was
stirred at rt and after 30 min the reaction was quenched
by addition of water (10 mL) and Et2O (60 mL). After
phase separation the organic phase was dried and con-
centrated to yield crude (S)-dictyoprolene (S)-1 (e.e.
91%). Without further isolation, the residue was dis-
solved in MeOH (150 mL) and K2CO3 (6.0 g, 10 mmol)
was added at 0°C. After 3 h at 0°C, the reaction
mixture was filtered through a plug of Celite-545 and
the solvent was evaporated. Flash chromatography
1
as a colourless liquid (12.9 g, 83%). H NMR (360.13
MHz, CDCl3): l=0.89 (3H, t, J=6.6), 1.19–1.23 (6H,
t, J=7.1), 1.28–1.37 (6H, m), 2.01–2.07 (2H, m), 2.37–
2.40 (2H, t, J=6.2), 3.47–3.55 (2H, m), 3.61–3.68 (2H,
m), 4.47 (1H, t, J=5.8), 5.37–5.42 (1H, m), 5.48–5.51
(1H, m). 13C NMR (90 MHz, CDCl3): l=14.1, 15.3,
22.6, 27.5, 29.3, 31.6, 32.1, 61.2, 102.7, 123.8, 132.4.
Spectroscopic data were in full agreement with those
previously reported.29
4.2.3. rac-1,5-Undecadien-3-ol rac-6. To a stirred solu-
tion of acetal 5 (7.0 g, 32.7 mmol) in pentane (100 mL),
HCOOH conc. (20 mL) was slowly added at −40°C.
After complete addition of HCOOH, the reaction mix-
ture was allowed to warm up to rt. When first traces of
side products were detected (ca. 30 min, monitored via
TLC) work-up was immediately started although full
conversion was not reached. The reaction mixture was
cooled to −50°C and the solvent (containing product)
was decanted. The solids (HCOOH) were washed with

A. Wallner et al. / Tetrahedron: Asymmetry 14 (2003) 2427–2432
2431
(pet. ether/EtOAc, 20:1) afforded (S)-6 [0.96 g, 96%,
Acknowledgements
[h]2D0=−2.8 (c 1.45, CHCl3, e.e. 91%)].
We wish to express our cordial thanks to H. Sterk
(University of Graz) for skilful assistance in NMR
spectroscopy. This research was performed within the
Spezialforschungsbereich Biokatalyse (SFB-A4, project
no. F-104) and was financed by the Fonds zur
Fo¨rderung der wissenschaflichen Forschung.
4.2.6. Kinetic resolution of rac-1,5-undecadien-3-ol rac-6.
Lipase Amano PS (2 g) was dispersed in hexane (70
mL), and after addition of rac-6 (1.75 g, 10.4 mmol)
and vinyl acetate (2.0 g, 23.2 mmol) the mixture was
agitated on an orbit shaker (rt, 120 rpm). The reaction
was monitored by GC on a chiral stationary phase.
When the conversion had reached 41% (7 h), the bio-
catalyst was filtered off and the solution was concen-
trated in vacuo. The residue was purified via flash
chromatography (pet. ether/EtOAc, 20:1) to afford (S)-
1 [0.45 g, [h]2D0=+12.0 (c 1.40, CHCl3, e.e. 98%)] and
(R)-6 [0.71 g, [h]2D0=+1.0 (c 1.48, CHCl3, e.e. 78%)].
Spectroscopic data of (S)-dictyprolene (S)-1 were in
full agreement with those previously reported.4
References
1. Moore, R. E. Acc. Chem. Res. 1977, 10, 40–47.
2. Boland, W.; Mueller, D. G. Tetrahedron Lett. 1987, 28,
307–310.
3. Yamada, K.; Tan, H.; Tatematsu, H. J. Chem. Soc.,
Chem. Commun. 1979, 572–573.
4. Yamada, K.; Tan, H.; Tatematsu, H.; Ojika, M. Tetra-
hedron 1986, 42, 3775–3780.
4.2.7. Kinetic resolution of rac-dictyoprolene rac-1.
Lipase Amano PS (2 g) was dissolved in phosphate-
buffer (200 mL, 100 mM, pH 8.0) and rac-1 (1.0 g, 4.8
mmol) was added. The reaction was monitored by GC
on a chiral stationary phase. When the conversion had
reached 55% (30 min), the aqueous layer was extracted
with Et2O (3×40 mL) and the organic phase was dried
and concentrated in vacuo. The residue was purified via
flash chromatography (pet. ether/EtOAc, 20:1) to
afford (R)-1 [0.31 g, [h]2D0=−14.4 (c 1.53, CHCl3, e.e.
80%)] and (S)-6 [0.35 g, [h]2D0=−2.0 (c 1.32, CHCl3, e.e.
71%)].
5. For a related chemoenzymatic synthesis based on kinetic
resolution see: Yamamoto, Y.; Akakabe, Y.; Matsui, K.;
Shimidsu, H.; Kajiwara, T. Z. Naturforsch. 1999, 54c,
1027–1032.
6. Bornscheuer, U. T.; Kazlauskas, Hydrolases in Organic
Synthesis, Wiley-VCH: Weinheim, 1999; Chapter 5, p. 65
ff.
7. Faber, K. Biotransformations in Organic Chemistry, 4th
ed.; Springer Verlag: Heidelberg, 2000; p. 351.
8. Faber, K. Chem. Eur. J. 2001, 7, 5004–5010.
9. Fukumura, T. Agric. Biol. Chem. 1977, 41, 1327–1330.
10. Tokuyama, S.; Hatano, K. Appl. Microbiol. Biotechnol.
1996, 44, 774–777.
11. Ogawa, J.; Shimizu, S. In Stereoselective Biocatalysis;
Patel, R. N., Ed.; Marcel Dekker: New York, 2000; pp.
1–21.
12. Keith, J. M.; Iarrow, J. F.; Jacobsen, E. N. Adv. Synth.
Catal. 2001, 343, 5–26.
13. Huerta, F. F.; Minidis, A. B. E.; Ba¨ckvall, J.-E. Chem.
Soc. Rev. 2001, 30, 321–331.
14. El Gihani, M. T.; Williams, J. M. J. Curr. Opinion Chem.
Biol. 1999, 3, 11–15.
15. Persson, B. A.; Larsson, A. L. E.; Le Ray, M.; Ba¨ckvall,
J.-E. J. Am. Chem. Soc. 1999, 121, 1645–1650.
16. Kim, M.-J.; Choi, Y. K.; Choi, M. Y.; Kim, M. J.; Park,
J. J. Org. Chem. 2001, 66, 4736–4738.
4.3. General procedure for the lipase-screening of rac-6
Alcohol rac-6 (10 mL) was dissolved in hexane (1 mL)
and lipase (100 mg) and vinyl acetate (120 mL) were
added. The mixtures were incubated at 30°C with shak-
ing at 120 rpm and the reactions were monitored by
TLC and GC. For GC analysis the biocatalyst was
removed by centrifugation and the organic phase was
directly analyzed. Peak areas were corrected by the
molar response factor of 6/1 on FID using a calibration
curve.
4.4. Chiral analysis
17. Mitsuda, S.; Umemura, T.; Hirohara, H. Appl. Microbiol.
Biotechnol. 1988, 29, 310–315.
18. Danda, H.; Nagatomi, T.; Maehara, A.; Umemura, T.
Tetrahedron 1991, 47, 8701–8716.
19. Allylic alcohols form a dead-end complex with the transi-
tion metal catalyst thus blocking the reversible hydride-
transfer required for racemisation.
20. Va¨nttinen, E.; Kanerva, L. T. Tetrahedron: Asymmetry
1995, 6, 1779–1786.
Enantiomeric excesses were analyzed by GC on a chiral
stationary phase. rac-dictyoprolene rac-1 could be sep-
arated after following procedure: Column A [14 psi, H2,
110°C (iso), tR1=5.2 min (3R), tR2=6.2 min (3S)]. For
alcohol rac-6 direct chiral separation was not possible
and its enantiomeric composition was analyzed after
derivatization as the corresponding acetate 1.
21. Pedragosa-Moreau, S.; Morisseau, C.; Baratti, J.; Zylber,
J.; Archelas, A.; Furstoss, R. Tetrahedron 1997, 53, 9707–
9714.
4.5. Determination of absolute configuration
The absolute configuration of (S)-dictyoprolene (S)-1
was elucidated by comparison of optical rotation values
with literature data: [h]2D5=+11.1 (c 1.17, CHCl3).4 The
absolute configuration of (S)-1,5-undecadien-3-ol 6 was
deduced from that of (S)-1.
22. Hirohara, H.; Nishizawa, M. Biosci. Biotechnol. Biochem.
1998, 62, 1–9.
23. Yamano, T.; Kikumoto, F.; Yamamoto, S.; Miwa, K.;
Kawada, M.; Ito, T.; Ikemoto, T.; Tomimatsu, K.;
Mizuno, Y. Chem. Lett. 2000, 448–449.

2432
A. Wallner et al. / Tetrahedron: Asymmetry 14 (2003) 2427–2432
1992, 7, 13–27. For a review see: Straathof, A. J. J.;
Jongejan, J. A. Enzyme Microb. Technol. 1997, 21, 559–571.
28. Xu, G.; Liu, Y.; Sayre, L. M. J. Org. Chem. 1999, 64,
5732–5745.
29. Kobayashi, Y.; Shimazaki, T.; Taguchi, H.; Sato, F. J. Org.
Chem. 1990, 55, 5324–5335.
24. Danda, H.; Maehara, A.; Umemura, T. Tetrahedron Lett.
1991, 32, 5119–5122.
25. Mitsunobu, O. Synthesis 1981, 1–28.
26. Mayer, S. F.; Steinreiber, A.; Orru, R. V. A.; Faber, K.
J. Org. Chem. 2002, 67, 9115–9121.
27. Straathof, A. J. J.; Rakels, J. L. L.; Heijnen, J. J. Biocatalysis