Selective ruthenium-catalyzed epimerization of chiral sec-alcohols

Article abstract of DOI:10.1016/j.cattod.2014.05.006

Extension of secondary alcohol racemization catalyzed by homogeneous half-sandwich ruthenium complexes to the epimerization of natural products containing additional non-functionalized stereo-centers has been investigated. Ruthenium-catalysed epimerization of the sec-alcohols (-)-menthol, (-)-isopulegol, (+)-borneol, (+)-fenchol and cholesterol under mild reaction conditions and low catalyst loadings (2 mol%) provides rapid access to their less abundant diastereoisomers (+)-neomenthol, (+)-neoisopulegol, isoborneol, beta-fenchol and epicholesterol in admixture with the parent diastereomers in ratios ranging from 1:4.9 to 1:2.4 (epimer:parent).

Full text of DOI:10.1016/j.cattod.2014.05.006

Catalysis Today 241 (2015) 255–259
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Catalysis Today
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Selective ruthenium-catalyzed epimerization of chiral sec-alcohols
∗
Otto Långvik, Denys Mavrynsky, Reko Leino
Laboratory of Organic Chemistry, Åbo Akademi University, 20500 Åbo, Finland
a r t i c l e i n f o
a b s t r a c t
Article history:
Extension of secondary alcohol racemization catalyzed by homogeneous half-sandwich ruthenium
complexes to the epimerization of natural products containing additional non-functionalized stereo-
centers has been investigated. Ruthenium-catalysed epimerization of the sec-alcohols (−)-menthol,
Received 14 November 2013
Received in revised form 2 May 2014
Accepted 4 May 2014
(
−)-isopulegol, (+)-borneol, (+)-fenchol and cholesterol under mild reaction conditions and low catalyst
Available online 23 July 2014
loadings (2 mol%) provides rapid access to their less abundant diastereoisomers (+)-neomenthol, (+)-
neoisopulegol, isoborneol, beta-fenchol and epicholesterol in admixture with the parent diastereomers
in ratios ranging from 1:4.9 to 1:2.4 (epimer:parent).
Keywords:
Epimerization
Terpenoids
©
2014 Elsevier B.V. All rights reserved.
sec-Alcohol
Homogeneous catalysis
Ruthenium
1
. Introduction
stereocenters (Scheme 1). In such cases, only the hydroxyl contain-
ing stereocenter is expected to interconvert in the presence of the
ruthenium catalyst, making the epimerization processes essentially
analogous to racemization.
Configurational interconversion of secondary carbinol based
stereogenic centers takes place in the presence of some transition
metal catalysts, for example homogeneous half-sandwich ruthe-
nium complexes [1–6]. Such processes have particular relevance
for dynamic kinetic resolution (DKR) of sec-alcohols, where often a
homogeneous ruthenium catalyst used for in situ alcohol racemiza-
tion in the presence of a resolving enzyme, such as CAL-B, enables
the shift from conventional kinetic resolution to DKR providing, in
optimal cases, chiral products in up to 100% yields and enantiomeric
excesses [7–11]. Thus, with highly active racemization catalysts
under optimized reaction conditions, short reaction times together
with excellent selectivities and yields can be reached. In such pro-
cesses, utilizing homogeneous half-sandwich ruthenium catalysts,
the racemization of sec-alcohol stereocenters has been shown to
involve an oxidation-reduction (dehydrogenation-hydrogenation)
sequence, where hydrogen transfer from ruthenium to a coor-
dinated ketone, initially formed by ␤-hydride elimination of the
sec-alcohol derived ruthenium alkoxide, takes place with equal
probabilities from both enantiofaces of the C O bond resulting in
efficient configurational interconversion [12–14].
Related epimerization reactions have been reported for some
saccharides catalyzed by homogeneous half-sandwich ruthenium
complexes [15], for terpenoids by homogeneous and heteroge-
neous catalyst systems [16,17], and for steroid type structures by
homogeneous half-sandwich rhenium catalyst [17].
In both resolution processes and chemical or enzymatic synthe-
sis, undesired stereoisomers are frequently formed as byproducts,
requiring separation and/or recycling. The development of new
benign, selective and efficient epimerization processes is, there-
fore, valuable in improving the overall efficiencies of synthetic
strategies [17]. Further, such processes may also have industrial
significance as demonstrated here by the homogeneously cat-
alyzed epimerization of menthol, which at least in theory could be
applied for epimerization of the undesired stereoisomer in the syn-
thetic production of (−)-menthol [16]. Moreover, in principle, such
inversions of single stereocenters in chiral compounds contain-
ing multiple stereogenic centers could potentially be utilized for
conversion of inexpensive starting materials into diastereomeric
mixtures from which more valuable compounds could be isolated
by conventional separation techniques, provided that the result-
ing equilibrium mixture contains sufficient amounts of the desired,
rare stereoisomer. Ideally, such processes could be envisioned to
become dynamic (similar to DKRs) in the presence of a suitable
enzyme catalyst. In theory, catalytic epimerization processes could
even be applied in multistep total syntheses of complex natural
products, where other efficient methods for obtaining the desired
In the present work, we have investigated the potential
extension of sec-alcohol racemization catalyzed by homogeneous
half-sandwich ruthenium complexes to the epimerization of sec-
carbinol natural products containing additional non-functionalized
∗ Corresponding author. Tel.: +358 2 215 4132.
E-mail address: reko.leino@abo.fi (R. Leino).
http://dx.doi.org/10.1016/j.cattod.2014.05.006
0
920-5861/© 2014 Elsevier B.V. All rights reserved.

2
56
O. Långvik et al. / Catalysis Today 241 (2015) 255–259
R
3. Results and discussion
R
R
Production of pharmaceutically useful, otherwise desired or
expensive stereoisomers of natural or non-natural products
by simple-to-operate, cost effective and rapid catalytic meth-
ods is an appealing approach. In this work, two previously
disclosed highly active homogeneous ruthenium catalysts, dicar-
bonylchloro(pentabenzylcyclopentadienyl)ruthenium (1) [11] and
dicarbonylchloro(pentaphenylcyclopentadienyl)ruthenium (2) [6],
were used for epimerization of (−)-menthol [(R)-3] and (−)-
isopulegol [(R)-4]. Further, three other structurally different natural
products, (+)-borneol [(S)-5], (+)-fenchol [(R)-6] and cholesterol
R
R1
*
R1
*
R
Ru Cl
OC CO
OH
OH
*
R = Bn (1), Ph (2)
*
*
2
2
R
epimerization
R
Scheme 1. Proposed epimerization of sec-alcohol natural products with half-
sandwich ruthenium catalysts 1 and 2.
[
(S)-7] were epimerized using catalyst 1. The results of the epimer-
ization reactions are collected in Table 1. For the sake of clarity, the
stereochemical descriptors used here for the chiral alcohols refer
to the hydroxyl group containing stereocenters only, expected to
undergo epimerization in the presence of the ruthenium catalysts,
with the descriptors for the configurationally stable stereocen-
ters being omitted. All starting materials employed in this work
are biologically active or otherwise useful for various commercial
applications. For example, the global demand for menthol, obtained
both by synthetic processes and isolation from natural sources,
and used in e.g., toothpaste, dietary products and cough drops,
exceeds 20,000 metric tons per year [18]. Nevertheless, also the
non-natural or naturally occurring rare stereoisomers exhibit in
some cases useful and desirable properties with potential applica-
tions [19–21]. In addition, various terpenoid-type compounds have
been shown to possess interesting biological activities, including
anti-inflammatory, antitumor, induced apoptosis and other poten-
tial applications in cancer treatment [22–25]. The production or
isolation of the rare stereoisomers is, however, seldom trivial due
to their low abundance, difficult isolation or complex and expensive
synthetic processes.
configuration of a sec-alcohol based stereocenter prove inapplica-
ble.
2
. Materials and methods
All glassware was oven dried and cooled in desiccator over
phosphorous pentoxide prior to use. All starting materials and
solvents, except cholesterol, were purified by removal of possi-
ble water traces originating from storage at ambient conditions.
Potassium tert-butoxide (t-BuOK) was sublimated in vacuum
prior to use. Tetrahydrofuran (THF) was distilled directly from
sodium/benzophenone ketyl under argon. The chiral alcohols
(
−)-menthol [(R)-3] (>99%, Fluka AG, Buchs, Switzerland), (−)-
isopulegol [(R)-4] (>99%, SAFC Supply Solutions, St. Louis, USA),
+)-borneol [(S)-5] (>98%, Naarden International), (+)-fenchol [(R)-
] (>95%, Fluka AG, Buchs, Switzerland) and cholesterol [(S)-7]
99%, SigmaChemicals, St. Louis, MO, USA) were all obtained from
(
6
(
commercial sources. Of the starting materials, (−)-menthol was
recrystallized from chloroform and (+)-borneol was predried over
The configurational inversion of the C*(H)(OH) stereocen-
ter in the readily available natural products (R)-3 and (R)-4
under mild reaction conditions and low catalyst loadings
4
A˚ molecular sieves in stock solution (THF) for >24 h prior to
use, (−)-isopulegol was redistilled under dry conditions (Ar atmo-
sphere) and stored in a glovebox. Epimerization catalysts 1 and
(2 mol%) would ideally provide rapid catalytic access to the
2
were prepared as described in the literature with spectroscopic
rare diastereomeric terpenoids (S)-3 and (S)-4. In the ini-
tial epimerization experiments with (R)-3 and (R)-4 using the
pentabenzyl(cyclopentadienyl)ruthenium complex as the catalyst,
diastereomeric mixtures of (R)-3/(S)-3 and (R)-4/(S)-4 were indeed
obtained in 3:1 and 6:1 ratios, respectively, within a few hours.
The first experiments were carried out under strictly anhydrous
atmosphere in a glove box at ambient temperature, ensuring inert
data identical to those reported previously [6,11].
In a typical epimerization experiment, 20 ␮mol of the corre-
sponding catalyst was dissolved in THF (2 mL) and transferred to
a Schlenk tube. A magnetic stirring bar and 0.25 M solution of t-
BuOK in THF (100 ␮L, 25 ␮mol) were added. Activation time for
the catalyst was 20 min, during which the tube was closed with
a stopper and removed from the glovebox. Next, 2 mL of a 0.50 M
stock solution of the starting material (1 mmol) was added to the
(water and oxygen free) reaction conditions. In these reactions,
the diastereomeric ratio reached remained unchanged for 18 h. For
demonstration of the proof-of-concept, the more expensive, minor
diastereomers were then separated and purified by conventional
column chromatography in 40–80% yields, based on their concen-
trations in the reaction mixtures (for details, see Section 2).
In a closer comparison of the catalysts 1 and 2 for epimeriza-
tion, the latter was found to be less efficient, providing with both
starting materials (R)-3 and (R)-4 diastereomeric mixtures of (R)-
3/(S)-3 and (R)-4/(S)-4 in 89/11 and 93/7 ratios, respectively, after
◦
Schlenk tube. The reaction mixture was stirred at 23 C and sam-
ples were taken either through a rubber septa or counter gas flow
using a degassed syringe and needle. The product distribution was
monitored by GC, GC/MS and/or NMR spectroscopy. Samples of
the reactions were filtered though a small pad of silica in order to
quench the reaction after which the sample was diluted and directly
analyzed. The GC apparatus used was Agilent Technologies 6850
GC equipped with a HP-1 column (30.0 m × 320 ␮m × 0.25 ␮m), H
2
as a carrier gas, and FID detector. The GC/MS apparatus used was
Agilent Technologies 7890 A GC equipped with 5975C MS detector
2
3 h (Table 1, entries 2 and 4). Furthermore, the longer reaction
times with catalyst 2 for starting materials (R)-3 and (R)-4 resulted
in cloudy reaction mixtures, likely due to the poor overall solubility
of catalyst 2 in common organic solvents as compared to 1. Thus, for
further experiments, catalyst 1 was selected, providing in all cases
fast and selective epimerizations. Epimerization of (−)-menthol in
the presence of 1 as a function of time is displayed in Fig. 1, demon-
strating the equilibrium mixture obtained, evident from analysis
of the shapes of the reaction concentration profiles after prolonged
reaction time.
(
EI), HP-5MS column (30 m × 250 ␮m × 0.25 ␮m) and He as a carrier
gas. The NMR spectra of the compounds were recorded on a Bruker
Avance 600 MHz NMR spectrometer equipped with a BBI-5 mm-
◦
1
Zgrad–ATM probe at 25 C operating at 600.13 MHz for H and
13
1
50.92 MHz for C using TMS (0.00 ppm) or CDCl3 (7.26 ppm) 1
NMR signals as reference. Isolation of the products was performed
by column chromatography using CH Cl -hexane mixture as the
H
2
2
eluent. The isolated yields of reaction products (+)-neomenthol
[
(S)-3] and (+)-neoisopulegol [(S)-4] were 32 mg (20%) and 10 mg
For broadening of the substrate scope, other readily avail-
able secondary alcohols (+)-borneol [(S)-5], (+)-fenchol [(R)-6] and
(
6%), respectively.

O. Långvik et al. / Catalysis Today 241 (2015) 255–259
257
Table 1
Epimerization reactions of the naturally occurring chiral alcohols 3–7 in the presence of ruthenium catalyst 1 or 2 (2 mol%) and t-BuOK (2.5 mol%) in THF at 23 C.
◦
Entry
Catalyst
Starting material
Epimer
Diastereomer ratio
1
2
1
2
(R)-3/(S)-3 75/25a
(R)-3/(S)-3 89/11a
(
R)-3
R)-4
(
S)-3
OH
OH
OH
OH
3
4
1
2
(R)-4/(S)-4 84/16a
(R)-4/(S)-4 93/7a
(
S)-4
(
(
R)-5
5
1
1
(S)-5
(S)-5/(R)-5 71/29b
OH
H
H
OH
(
R)-6
H
H
(S)-6
OH
(R)-6/(S)-6 82/18b
6
OH
H
H
(
R)-7
(
S)-7
H
(S)-7/(R)-7c 78/22b
7
1
H
H
H
H
H
HO
HO
a
Reaction time 23 h.
Reaction time 21 h.
Catalyst loading 7 mol%.
b
c
cholesterol [(S)-7] from the chiral pool were investigated using 1 as
the epimerization catalyst. In all cases, stable concentration profiles
similar to those shown in Fig. 1 were observed after few hours of
reaction, although all reactions were continued for 23 h in order to
ensure that true equilibrium values were reached. Here, for men-
thol and isopulegol 75/25 and 84/16 epimer ratios for (R)-3/(S)-3
and (R)-4/(R)-4, respectively, were observed after 23 h (Table 1,
entries 1 and 3). For borneol and fenchol, 71/29 and 82/18 ratios
of (S)-5/(R)-5 and (R)-6/(S)-6, respectively, were obtained (Table 1,
entries 5 and 6). Finally, for cholesterol the epimerization with 1
provided, after 21 h, a 78/22 ratio of cholesterol (S)-7 and epicholes-
terol (R)-7 (Table 1, entry 7). In this case, slightly higher catalyst
loading (7 mol%) was employed due to the smaller amount of start-
ing material applied in the reaction.
Turnover frequency values (TOF = [mol of converted alco-
−
1
−1
hol] [mol of Ru] [s] ) were then calculated for the reproduced
◦
reactions performed using catalyst 1 at 23 C. As expected,
−
1
(
−)-menthol exhibited the highest TOF value, 0.003 s
(60 min
Fig. 1. Epimerization of (−)-menthol (᭹) producing (+)-neomenthol (ꢀ) with 1
◦
sample). Both (+)-borneol and (−)-isopulegol (60 min sam-
(
2 mol%) at 23 C.
−
1
−1
and 0.00029 s ,
ples) exhibited lower TOF values, 0.0015 s

2
58
O. Långvik et al. / Catalysis Today 241 (2015) 255–259
Table 2
respectively. The evidently lower TOF value for (−)-isopulegol
could possibly be a consequence of the double bond present in
the starting material. Conclusively, the equilibria for the epimer-
ization reactions were reached within a reasonable reaction time,
after approximately 5 h, being sufficiently fast and resulting in a
viable process at low catalyst loading.
Heterogeneously catalyzed epimerizations of terpenoids have
been studied earlier [16,26]. A drawback with the heterogeneous
catalyst systems is, however, the formation of oxidized menthone
intermediate, resulting in isomenthol which lowers the selectivity
of the epimerization process. In the present work employing homo-
geneous Ru-based epimerization catalysts, byproducts, including
isomenthol diastereoisomers potentially originating from keto-
enol tautomerization of menthone, were not observed within the
limits of GC detection. Moreover, for (−)-menthol, the utiliza-
tion of an oxidation-reduction sequence forming (+)-neomenthol,
Equilibrium constants for the epimerization of (−)-menthol to (+)-neomenthol.
Entry
T [K]
Eneo-m
1
2
3
4
5
296
323
423
448
473
3.0
2.9
a
2.3
2.0
a
a
1.9
a
Ref. [16].
not directly comparable with the values obtained in present
work.
Notably, at least in principle, the epimerization processes
studied here could also be converted into dynamic methods by
combining the epimerization catalyst with a suitable (e.g., acylat-
ing) enzyme, in which case the reaction could possibly be shifted
toward the selective formation and isolation of the energetically
less stable diastereomer or its derivative. Alternatively, in a static
fashion, the desired minor product can be separated and isolated
from the initially formed equilibrium mixture, as demonstrated
in the present work and the remaining major component re-
epimerized by addition of a new batch of the ruthenium catalyst.
(
+)-isomenthol and (+)-neoisomenthol diastereomers has been
reported earlier [27]. In addition, oxidation combined with selec-
tive reduction has been demonstrated for camphor [28,29]. An
obvious advantage with the selective catalytic epimerization with
homogeneous catalysts, such as 1, is the one step reaction with-
out the need for isolation of reaction intermediates, combined with
fully selective epimerization reaction without detectable formation
of side products.
4. Summary and conclusions
Here, it can be emphasized that epimerizations of diastereoiso-
mers are unlikely to produce equal amounts of the two
stereoisomers, in contrast to what would be the case with two
enantiomers using achiral catalysts. The thermodynamic equi-
librium for epimerization reactions will be shifted toward the
thermodynamically more stable diastereoisomer, which, in turn, is
depending on the molecular structure and its interactions with the
surrounding reaction media and the catalyst. In all five cases stud-
ied here, the predominantly formed diastereoisomer is the same as
the more abundant one found in Nature. The inspiring and impres-
sive ability of Nature to synthesize single stereoisomers in high
selectivity is well documented, exemplified by the biosynthesis of
menthol [30]. Interestingly, formation of the chemically least stable
chiral center, containing the hydroxyl group, is the last step in men-
thol biosynthesis. Moreover, two different enzymes are involved
in reduction of the menthone precursor yielding both (−)-menthol
The objective of this work was the selective epimerization
of readily available chiral secondary alcohols from the chi-
ral pool, (−)-menthol, (−)-isopulegol, (+)-borneol, (+)-fenchol
and cholesterol into more valuable diastereomers by a sim-
ple to operate, rapid and cost efficient catalytic method.
For such compounds, containing a single sec-carbinol stere-
ocenter together with other non-functionalized stereogenic
centers, the epimerization reactions closely resemble the cat-
alytic racemizations of sec-alcohols employed in chemoenzymatic
dynamic kinetic resolutions. The results obtained here using
dicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium as the
epimerization catalyst demonstrate that for these naturally occur-
ring chiral alcohols equilibrium mixtures of two diastereomers are
rapidly formed at low catalyst loadings at ambient temperature. In
two cases, with (−)-menthol and (−)-isopulegol, feasibility of iso-
lation of the corresponding rare diastereoisomers (+)-neomenthol
and (+)-neoisopulegol from the equilibrium mixtures was also
demonstrated. Further development of the methodology described
herein may provide inexpensive and practical catalytic routes, after
diastereomer separation and purification or as a dynamic method
in combination with a suitable enzyme catalyst, for conversion of
inexpensive chiral pool starting materials into more valuable ones.
(
in large excess) and (+)-neomenthol, respectively [30,31]. Further-
more, Nature has the ability to perform an additional separation
of the two diastereoisomers formed by using specific transferase
enzymes [31].
Finally, some epimerization experiments at slightly elevated
◦
temperature (50 C) were performed using (R)-3 as the starting
◦
material. The equilibrium concentrations at 50 C [2.9:1, (R)-3:(S)-
3
] were, however, within experimental error similar to those
◦
obtained at 23 C [3.0:1, (R)-3:(S)-3]. While the thermodynamic
equilibrium constants would be expected to shift by changes in the
reaction temperature, the increase here was incremental only and
considerably higher temperatures, possibly in a pressurized reac-
tor, would be required for further studying the influence of reaction
conditions.
Acknowledgements
Financial support from the Finnish Funding Agency for Inno-
vation (TEKES) (Technology Programme SYMBIO project no.
0168/07: Developing New Chemoenzymatic Methods and Biocat-
4
Equilibrium constants (Eneo-m) for (−)-menthol epimerization
reactions carried out at different temperatures are presented in
Table 2. The agreement of the Eneo-m calculated for the (R)-3/(S)-3
equilibrium (Table 2, entry 1 and 2) is satisfactory when compared
with the literature values (Table 2, entry 3–5) from the related
work by Etzold and co-workers [16]. Nevertheless, for complete
characterization of the kinetic and thermodynamic aspects of the
epimerization reactions further experiments would be needed.
Additionally, in earlier studies the mole fractions for (R)-3/(S)-3
and (S)-5/(R)-5 at equilibrium have been determined as 85.5/14.5
and 90.5/9.5, respectively [32]. These values were, however, mea-
sured for compounds in the gas phase at 500 K and are thus
alysts) and the Makarna Olins Stipendiefond at the Student Union of
Åbo Akademi University and the Rector of Åbo Akademi University
(to O.L.) is gratefully acknowledged.
References
[
1] Y. Ahn, S.-B. Ko, M.-J. Kim, J. Park, Coord. Chem. Rev. 252 (2008) 647–658.
[2] M. Merabet-Khelassi, N. Vriamont, L. Aribi-Zouioueche, O. Riant, Tetrahedron:
Asymmetry 22 (2011) 1790–1796.
[
3] A. Parvulescu, J. Janssens, J. Vanderleyden, D. De Vos, Top. Catal. 53 (2010)
31–941.
9
[4] S. Wuyts, D.E. De Vos, F. Verpoort, D. Depla, R. De Gryse, P.A. Jacobs, J. Catal. 219
(2003) 417–424.

O. Långvik et al. / Catalysis Today 241 (2015) 255–259
259
[
[
5] K. Yamaguchi, T. Koike, M. Kotani, M. Matsushita, S. Shinachi, N. Mizuno, Chem.
Eur. J. 11 (2005) 6574–6582.
6] B. Martín-Matute, M. Edin, K. Bogár, F.B. Kaynak, J.-E. Bäckvall, J. Am. Chem. Soc.
[20] Y. Yuasa, A. Nagakura, H. Tsuruta, J. Agric. Food Chem. 49 (2001) 5013–5018.
[21] D.A. Mannock, R.N.A.H. Lewis, T.P.W. McMullen, R.N. McElhaney, Chem. Phys.
Lipids 163 (2010) 403–448.
1
27 (2005) 8817–8825.
[22] M.M. Ehrnhöfer-Ressler, K. Fricke, M. Pignitter, J.M. Walker, J. Walker, M. Rych-
lik, V. Somoza, J. Agric. Food Chem. 61 (2013) 3451–3459.
[23] A. Jaafari, M. Tilaoui, H.A. Mouse, L.A. M’bark, R. Aboufatima, A. Chait, M. Lep-
oivre, A. Zyad, Braz. J. Pharmacogn. 22 (2012) 534–540.
[24] S.-Y. Paik, K.-H. Koh, S.-M. Beak, S.-H. Paek, J.-A. Kim, Biol. Pharm. Bull. 28 (2005)
802–807.
[
[
[
7] O. Pàmies, J.-E. Bäckvall, Chem. Rev. 103 (2003) 3247–3261.
8] J.H. Lee, K. Han, M.-J. Kim, J. Park, Eur. J. Org. Chem. (2010) 999–1015.
9] B. Martín-Matute, J.-E. Bäckvall, Curr. Opin. Chem. Biol. 11 (2007) 226–232.
[
10] B. Martín-Matute, M. Edin, K. Bogár, J.-E. Bäckvall, Angew. Chem. Int. Ed. 43
2004) 6535–6539.
11] D. Mavrynsky, L.T. Kanerva, R. Sillanpää, R. Leino, Pure Appl. Chem. 83 (2011)
79–487.
(
[
[25] M. Nasuda, M. Ohmori, K. Ohyama, Y. Fujimoto, Chem. Pharm. Bull. 60 (2012)
681–685.
4
[
[
12] M.C. Warner, O. Verho, J.-E. Bäckvall, J. Am. Chem. Soc. 133 (2011) 2820–2823.
13] O. Verho, E.V. Johnston, E. Karlsson, J.-E. Bäckvall, Chem. Eur. J. 17 (2011)
[26] T. Yoshida, A. Komatsu, M. Indo, Agric. Biol. Chem. 29 (1965) 824–831.
[27] S.A. Haut, J. Agric. Food Chem. 33 (1985) 278–280.
[28] P.S. Bahia, M.A. Jones, J.S. Snaith, J. Org. Chem. 69 (2004) 9289–9291.
[29] Y. Moglie, F. Alonso, C. Vitale, M. Yus, G. Radivoy, Tetrahedron 62 (2006)
2812–2819.
[30] R.B. Croteau, E.M. Davis, K.L. Ringer, M.R. Wildung, Naturwissenschaften 92
(2005) 562–577.
[31] R. Kjonaas, C. Martinkus-Taylor, R. Croteau, Plant Physiol. 69 (1982) 1013–1017.
[32] G.J. Kabo, M.L. Frenkel, J. Chem. Thermodyn. 15 (1983) 377–381.
1
1216–11222.
[
[
14] M.C. Warner, J.-E. Bäckvall, Acc. Chem. Res. 46 (2013) 2545–2555.
15] C. Ramstadius, A.M. Träff, P. Krumlinde, J.-E. Bäckvall, I. Cumpstey, Eur. J. Org.
Chem. (2011) 4455–4459.
16] B. Etzold, A. Jess, M. Nobis, Catal. Today 140 (2009) 30–36.
17] I. Saura-Llamas, J.A. Gladysz, J. Am. Chem. Soc. 114 (1992) 2136–2144.
18] M. McCoy, Chem. Eng. News 88 (35) (2010) 15–16.
[
[
[
[
19] D.P. de Sousa, E. Raphael, U. Brocksom, T.J. Brocksom, Z. Naturforsch., C: J. Biosci.
6
2 (2007) 563–566.