Synthesis of (?)-Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)-Catalyzed Cycloisomerization

Article abstract of DOI:10.1002/anie.201601834

The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of a highly stereoselective gold(I)-catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone.

Full text of DOI:10.1002/anie.201601834

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International Edition: DOI: 10.1002/anie.201601834
German Edition: DOI: 10.1002/ange.201601834
Total Synthesis
Synthesis of (À)-Cannabimovone and Structural Reassignment of
Anhydrocannabimovone through Gold(I)-Catalyzed
Cycloisomerization
Javier Carreras, Mariia S. Kirillova, and Antonio M. Echavarren*
Dedicated to Professor Miquel A. Pericàs on the occasion of his 65th birthday
Abstract: The first total synthesis of cannabimovone from
Cannabis sativa and anhydrocannabimovone was achieved by
means of a highly stereoselective gold(I)-catalyzed cyclo-
isomerization. The results led to reassignment of the structure
of anhydrocannabimovone.
A structurally different cannabinoid named cannabimo-
vone (3) has recently been isolated by the groups of
Taglialatela-Scafati and Appendino from a nonpsychotropic
variety of hemp (Cannabis sativa L.; Figure 1).[9] In their
attempt at preparing 3 from CBD (2) through an intra-
molecular aldol reaction of keto aldehyde 4 under mild acidic
conditions, the product of dehydration (5) was formed instead
(Scheme 1). Under basic conditions, the novel cannabinoid
T
he herbaceous plant Cannabis sativa has been used in
medicine for centuries and still attracts significant interest due
to the biological and pharmaceutical activity of many of its
metabolites.[1] More than 60 compounds, known as cannabi-
noids (a group of C21 terpenophenolic compounds), are
exclusively found in Cannabis sativa.[2] Owing to the develop-
ment of synthetic cannabinoids,[3,4] the unique components of
Cannabis sativa are known as phytocannabinoids. The most
abundant compound is D9-tetrahydrocannabinol (THC, 1;
Figure 1), which shows interesting pharmacological activity as
an analgesic, antiemetic, and appetite stimulant, among
others, besides its well-known psychotropic effects.[5] Several
total syntheses of 1 have been accomplished to date.[6]
Scheme 1. Synthesis of anhydrocannabimovone (6) from cannabidiol
(CBD, 2).[9]
Figure 1. Cannabinoids THC (1), CBD (2), and cannabimovone (3).
anhydrocannabimovone (6) was directly formed through an
intramolecular oxy-Michael addition of one of the phenol
groups to the intermediate enone. Synthetic 6 was found to be
active against metabotropic and ionotropic cannabinoid
receptors, showing a similar biological profile to THC,
whereas cannabimovone (3) has affinity only for ionotropic
receptors.[9]
Cannabidiol (CBD, 2) is another important phytocannabinoid
with great potential as a drug[7] since it modulates the
undesired effects of THC when they are administrated
together.[8]
The unprecedented abeo-menthane terpenoid structure of
cannabimovone (3) includes a densely functionalized cyclo-
pentane with four contiguous stereocenters. The novel
structure of 3, coupled with its lability towards dehydration
under acidic or basic conditions and the interesting biological
profiles of both 3 and 6, inspired us to develop a total
synthesis that could allow access to a wide variety of
analogues. Herein, we report the first total synthesis of
enantiopure cannabimovone (3) and also revise the structure
originally assigned to anhydrocannabimovone from trans-
fused 6’ to cis-tetrahydro-1H-cyclopenta[b]benzofuran 6. Our
[*] Dr. J. Carreras, M. S. Kirillova, Prof. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
Barcelona Institute of Science and Technology
Av. Països Catalans 16, 43007 Tarragona (Spain)
E-mail: aechavarren@iciq.es
Prof. A. M. Echavarren
Departament de Química Analítica i Química
Orgànica, Universitat Rovira i Virgili
C/ Marcel·li Domingo s/n, 43007 Tarragona (Spain)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under http://dx.doi.org/10.
1002/anie.201601834.
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Scheme 2. Retrosynthetic analysis for 3 and 6.
approach to the synthesis of these compounds relies on
a gold(I)-catalyzed cycloisomerization[10–15] of aryl-substituted
1,5-enyne 7, which could be obtained in a few steps from
commercially available (+)-methyl (S)-3-hydroxybutyrate (9;
Scheme 2).
The synthesis commenced with alkylation of the lithium
enolate of 9 with prenyl bromide to provide known compound
10 with excellent diastereoselectivity (98:2) by following
a slight modification of the reported procedure[16] (Scheme 3).
Protection of the alcohol of 10 as a silyl ether, conversion of
the ester into an aldehyde by a two-step procedure (DIBAL
reduction/Swern oxidation), and subsequent homologation
with the Ohira–Bestmann reagent led to 1,5-enyne 11 (31%
over 5 steps). Sonogashira coupling of 11 with iodo arene 12,
prepared in two steps from olivetol, gave 7 in 83% yield on
a multi-gram scale. The gold(I)-catalyzed cyclization of 1,5-
enyne 7 was highly solvent dependent. Exposing 7 to the
cationic gold(I) complex [(JohnPhos)Au(MeCN)]SbF6 in
CH2Cl2 led to bicyclic compound 13 (49%). A similar result
was obtained using other solvents such as Et2O or toluene.
Reaction in MeOH afforded methyl ether 14 (93%). How-
ever, when the reaction was performed in DMSO, cyclo-
pentene 8 was obtained in excellent yield (88%). This
reaction was performed up to a 2.1 g scale. A similar result
was observed when the reaction was performed in DMF
(79%). Presumably, the initial intermediate of the gold(I)-
catalyzed cyclization (Int) undergoes proton elimination
assisted by the solvent to give 8 after protodeauration.
Notably, the gold-catalyzed cyclization led exclusively to the
product with the correct relative configuration, thereby
setting two of the final four stereocenters.
Although deprotection of the TBS group of 8 followed by
oxidation of the alcohol to the methyl ketone could be carried
out uneventfully, isomerization to form the a,b-unsaturated
ketone failed under all the conditions we examined with this
and with other intermediates with different phenol protecting
groups. Fortunately, the desired functionality in the five-
membered ring could be introduced by epoxidation with m-
CPBA and NaHCO3 to exclusively form 15, followed by
Meinwald rearrangement with stoichiometric BF3·Et2O to
give ketone 16 (2,3-cis). Epimerization and cleavage of the
silyl ether was achieved with aqueous HCl to give 17
(Scheme 4). The relative configuration of 17 was determined
by NMR studies and was confirmed by preparation of the
Scheme 3. a) LDA, HMPA, prenyl bromide, THF, À708C to À108C,
3 h, 81%; b) TBSCl, DBU, CH2Cl2, 258C, 14 h, 89%; c) DIBAL-H,
Toluene, À788C to À508C, 4 h, 84%; d) Oxalyl chloride, DMSO, Et3N,
CH2Cl2, À608C to 258C, 1 h; e) Ohira–Bestmann reagent, K2CO3
MeOH, 258C, 5 h, 51% (2 steps); f) Pd(PPh3)2Cl2 (5 mol %), CuI
(10 mol %), Et3N/iPr2EtN (1:1), 258C, 16 h, 83%; g) [(JohnPhos)Au-
(MeCN)]SbF6 (5 mol %), CH2Cl2 1m, 258C, 30 min, 49%;
h) [(JohnPhos)Au(MeCN)]SbF6 (5 mol %), MeOH 1m, 258C, 30 min,
93%. i) [(JohnPhos)Au(MeCN)]SbF6 (5 mol %), DMSO 0.5m, 258C,
3 h, 88%. LDA=lithium diisopropylamide, HMPA=hexamethylphos-
phoramide, THF=tetrahydrofuran, TBSCl=tert-butylsilyl chloride,
DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DIBAL-H=diisobutylalane,
DMSO=dimethyl sulfoxide, JohnPhos=(2-biphenyl)-di-tert-butylphos-
phine.
same compound by a different route, namely cleavage of the
TBS group of 8 followed by epoxidation to give 18, which
underwent Meinwald rearrangement to provide 17. Diaste-
reoselective reduction of b-hydroxy ketone 17 by Saksena–
Evans reaction with NaBH(OAc)3 in CH2Cl2 afforded diol 19.
Protection with AllocCl, which proceeded with moderate
selectivity, followed by Dess–Martin oxidation gave protected
cannabimovone 20. Cleavage of the MOM groups using
MgBr2 and BnSH,[17] followed by Pd0 deprotection of the allyl
carbonate provided 3 (53% over 2 steps). The spectral data
and optical rotation of the synthetic cannabimovone (3)
matched those reported for the natural compound.[18]
Whereas the synthesis of 3 fully supported the assigned
configuration for all of the intermediates, a crystalline oxabi-
cycle intermediate 21 was obtained through treatment of
epoxide 18 with a Brønsted acid, which led to opening of the
epoxide and trapping of the benzylic carbocation by the free
alcohol (Scheme 5). The molecular structure of 21 was
determined by X-ray diffraction, which confirmed the relative
configuration between the isopropenyl and the hydroxyethyl
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Scheme 6. a) Ac2O, Et3N, DMAP, CH2Cl2, À308C, 1 h, 50% (56%
brsm); b) DMP, NaHCO3, CH2Cl2, 258C, 1 h, 73%; c) MgBr2, BnSH,
Et2O, 258C, 24 h, 82%; d) K2CO3, MeOH, 258C, 15 min, 60% (6) and
19% (6’’).
Scheme 4. a) mCPBA, NaHCO3, CH2Cl2, 08C to 258C, 3 h, 57%;
b) BF3·OEt2, THF, 258C, 30 min, 93%; c) HCl dil./THF, 258C, 1 h,
88%; d) TBAF, THF, 258C, 14 h, 83%; e) mCPBA, NaHCO3, CH2Cl2,
08C to 258C, 4 h, 58%; f) BF3·OEt2, THF, 258C, 1 h, 48%; g) NaBH-
(OAc)3, CH2Cl2, 258C, 48 h, 48% (77% brsm); h) AllocCl, TMEDA,
CH2Cl2, À408C, 1.5 h, 41% (72% brsm); i) DMP, NaHCO3, CH2Cl2,
258C, 1.5 h, 87%; j) MgBr2, BnSH, Et2O, 258C, 30 h, 62%; k) Pd(PPh3)4
(5 mol %), dimedone, THF, 258C, 1 h, 85%. mCPBA=m-chloroper-
benzoic acid, TBAF=tetrabutylammonium fluoride, Alloc=allyloxycar-
bonyl, TMEDA=tetramethylethylenediamine, DMP=Dess–Martin peri-
odinane.
Figure 2. X-Ray structures for 6 and 23.
1H NMR of the major isomer 6 was identical to that reported
for anhydrocannabimovone, very significant differences were
observed in the 13C NMR spectrum.[20] Furthermore, the
optical rotation of 6 ([a]2D2 =+ 40.68 (c = 0.29, CHCl3)) was
very different to that reported ([a]2D2 = À178 (c = 0.02,
CHCl3)).[9] The structure of anhydrocannabimovone (6) was
finally confirmed by X-ray diffraction[19] and its absolute
configuration was assigned on the basis of the X-ray structure
of
anhydrocannabimovone
2-bromobenzoate
(23;
Figure 2).[19]
In order to clarify the discrepancy between our structural
assignment and that originally reported,[9] we performed DFT
calculations to study the oxy-Michael cyclization. Under basic
conditions, oxy-Michael cyclization of the phenolate anion
leads to cis fusion, which is more favored than the trans
addition by 19.8 KcalmolÀ1 (Figure 3).[21] Furthermore, DFT
calculations were employed to predict the expected 13C NMR
chemical shifts of the different possible products.[22] Our data
were in better agreement with the cis-tetrahydro-1H-
cyclopenta[b]benzofuran structure for anhydrocannabimo-
vone (6).[20]
Scheme 5. a) m-ClC6H4CO2H, CH2Cl2, 258C, 1 h, 77%; b) ZnI2,
(NaBH4), (CH2Cl)2, 258C, 14 h, 63%. X-Ray structure for 21.
substituents.[19] Treatment of 21 with ZnI2 effected a pinacol
rearrangement to give ketone 17.
The synthesis of anhydrocannabimovone (6) was carried
out from acetate 22 by MOM cleavage followed by treatment
with K2CO3 to promote the oxy-Michael addition. Under
these conditions, two separable epimers (6 and 6’’) were
formed in a 4:1 ratio (Scheme 6). Surprisingly, although
In conclusion, we have accomplished the first total
synthesis of cannabimovone (3). The four stereogenic centers
of the target molecule were set up starting from the
stereogenic center present in commercially available
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[2] O. Aizpurua-Olaizola, U. Soydaner, E. Öztürk, D. Schibano, Y.
Simsir, P. Navarro, N. Etxebarria, A. Usobiaga, J. Nat. Prod.
2016, 79, 324 – 331.
[3] For example: a) R. A. Archer, W. B. Blanchard, W. A. Day,
D. W. Johnson, E. R. Lavagnino, C. W. Ryan, J. E. Baldwin, J.
Org. Chem. 1977, 42, 2277 – 2284; b) R. Mechoulam, N. Lander,
A. University, J. Zahalka, Tetrahedron: Asymmetry 1990, 1, 315 –
318; c) S. H. Burstein, C. A. Audette, A. Breuer, W. A. Devane,
S. Colodner, S. A. Doyle, R. Mechoulam, J. Med. Chem. 1992, 35,
3135 – 3141.
[4] a) D. D. Dixon, D. Sethumadhavan, T. Benneche, A. R. Banaag,
M. A. Tius, G. A. Thakur, A. Bowman, J. T. Wood, A. Mak-
riyannis, J. Med. Chem. 2010, 53, 5656 – 5666; b) F. Gläser, M. C.
Brçhmer, T. Hurrle, M. Nieger, S. Bräse, Eur. J. Org. Chem.
2015, 1516 – 1524.
[5] a) J. Zajicek, P. Fox, H. Sanders, D. Wright, J. Vickery, A. Nunn,
A. Thompson, Lancet 2003, 362, 1517 – 1526; b) K. R. Müller-
Vahl, H. Prevedel, K. Theloe, H. Kolbe, H. M. Emrich, U.
Schneider, Neuropsychopharmacology 2003, 28, 384 – 388; c) K.
Mackie, Annu. Rev. Pharmacol. Toxicol. 2006, 46, 101 – 122;
d) A. T. El-Alfy, K. Ivey, K. Robinson, S. Ahmed, M. Radwan,
D. Slade, I. Khan, M. ElSohly, S. Ross, Pharmacol. Biochem.
Behav. 2010, 95, 434 – 442; e) M. E. Lynch, F. Campbell, Br. J.
Clin. Pharmacol. 2011, 72, 735 – 744.
Figure 3. Energy profile (cis and trans) for the oxy-Michael cyclization.
DFT calculations (M06-2x/6-31G(d,p) (MeOH), DG (kcalmolÀ1).
[6] a) D. A. Evans, E. A. Shaughnessy, D. M. Barnes, Tetrahedron
Lett. 1997, 38, 3193 – 3194; b) B. M. Trost, K. Dogra, Org. Lett.
2007, 9, 861 – 863; c) L.-J. Cheng, J.-H. Xie, Y. Chen, L.-X. Wang,
Q.-L. Zhou, Org. Lett. 2013, 15, 764 – 767; d) M. A. Schafroth, G.
Zuccarello, S. Krautwald, D. Sarlah, E. M. Carreira, Angew.
Chem. Int. Ed. 2014, 53, 13898 – 13901; Angew. Chem. 2014, 126,
14118 – 14121; e) F. Klotter, A. Studer, Angew. Chem. Int. Ed.
2015, 54, 8547 – 8550; Angew. Chem. 2015, 127, 8667 – 8670.
[7] a) R. Mechoulam, L. A. Parker, R. Gallily, J. Clin. Pharmacol.
2002, 42, 11S – 19S; b) C. Scuderi, D. D. Filippis, T. Iuvone, A.
Blasio, A. Steardo, G. Esposito, Phytother. Res. 2009, 23, 597 –
602; c) E. Blessing, M. Steenkamp, J. Manzanares, C. Marmar,
Neurotherapeutics 2015, 12, 825 – 836.
(+)-methyl (S)-3-hydroxybutyrate (9) and by using a fully
diastereoselective gold(I)-catalyzed cyclization. Interestingly,
this is the first example of the cycloisomerization of simple
1,5-enynes into 3-vinylcyclopent-1-enes catalyzed by gold in
the context of natural product synthesis. We also synthesized
anhydrocannabimovone (6) and revised the stereochemistry
at the ring fusion by X-ray crystallography and DFT
calculations. This synthetic endeavor provides ready access
to 3 and 6, as well as other synthetic cannabinoids, for
biological testing.
[8] a) I. G. Karniol, I. Shirakawa, N. Kasinski, A. Pfeferman, E. A.
Carlini, Eur. J. Pharmacol. 1974, 28, 172 – 177; b) C. J. A.
Morgan, G. Schafer, T. P. Freeman, H. V. Curran, Br. J.
Psychiatry 2010, 197, 285 – 290; c) J. Sastre-Garriga, C. Vila, S.
Clissold, X. Montalban, Expert Rev. Neurother. 2011, 11, 627 –
637.
[9] O. Taglialatela-Scafati, A. Pagani, F. Scala, L. De Petrocellis, V.
Di Marzo, G. Grassi, G. Appendino, Eur. J. Org. Chem. 2010,
2067 – 2072.
[10] a) C. Nieto-Oberhuber, M. P. MuÇoz, S. López, E. JimØnez-
NfflÇez, C. Nevado, E. Herrero-Gómez, M. Raducan, A. M.
Echavarren, Chem. Eur. J. 2006, 12, 1677 – 1693; b) V. López-
Carrillo, N. Huguet, . Mosquera, A. M. Echavarren, Chem.
Eur. J. 2011, 17, 10972 – 10978.
[11] R. Dorel, A. M. Echavarren, Chem. Rev. 2015, 115, 9028 – 9072.
[12] Synthesis of indenes by cycloisomerization of 1,5-enynes: A.
Martínez, P. García-García, M. A. Fernµndez-Rodríguez, F.
Rodríguez, R. Sanz, Angew. Chem. Int. Ed. 2010, 49, 4633 –
4637; Angew. Chem. 2010, 122, 4737 – 4741.
Acknowledgements
We thank MINECO (Severo Ochoa Excellence Accredita-
tion 2014-2018 (SEV-2013-0319), and project CTQ2013-
42106-P), the European Research Council (Advanced Grant
No. 321066), the AGAUR (2014 SGR 818 and Beatriu de
Pinós Postdoctoral Fellowship to J. C.), and the ICIQ
Foundation. We thank the ICIQ X-ray Diffraction and
Chromatograpy units. We also thank Nfflria Huguet and
Verónica L. Carrillo (ICIQ) for additional experiments and
Dr. G. JimØnez-OsØs (Universidad de La Rioja) for computa-
tional advice.
Keywords: cannabinoids · cycloisomerization · gold ·
oxy-Michael reaction · total synthesis
[13] Total synthesis through gold- or platinum catalyzed cycloisome-
rization of 1,5-enynes: a) V. Mamane, T. Gress, H. Krause, A.
Fürstner, J. Am. Chem. Soc. 2004, 126, 8654 – 8655; b) Y. Harrak,
C. Blaszykowski, M. Bernard, K. Cariou, E. Mainetti, V.
Mouri›s, A.-L. Dhimane, L. Fensterbank, M. Malacria, J. Am.
Chem. Soc. 2004, 126, 8656 – 8657; c) A. Fürstner, P. Hannen,
Chem. Eur. J. 2006, 12, 3006 – 3019; d) A. Fürstner, A. Schlecker,
Chem. Eur. J. 2008, 14, 9181 – 9191; e) G. Lemi›re, V. Gandon, K.
Cariou, A. Hours, T. Fukuyama, A.-L. Dhimane, L. Fensterbank,
M. Malacria, J. Am. Chem. Soc. 2009, 131, 2993 – 3006.
How to cite: Angew. Chem. Int. Ed. 2016, 55, 7121–7125
Angew. Chem. 2016, 128, 7237–7241
[1] a) G. A. Thakur, R. I. Duclos Jr, A. Makriyannis, Life Sci. 2005,
78, 454 – 466; b) Marijuana and the Cannabinoids (Ed. M. A.
ElSohly), Humana, Totowa, NJ, 2007; c) P. J. Robson, Drug Test.
Anal. 2014, 6, 24 – 30; d) R. Mechoulam, L. O. Hanus, R.
Pertwee, A. C. Howlett, Nat. Rev. Neurosci. 2014, 15, 757 – 764;
e) Special issue, Nature 2015, 525, S1 – S18.
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[14] Total synthesis through gold-catalyzed Conia-type cyclizations
[18] See the Supporting Information for more details. Optical
of 1,5-enynes: a) S. T. Staben, J. J. Kennedy-Smith, D. Huang,
B. K. Corkey, R. L. LaLonde, F. D. Toste, Angew. Chem. Int. Ed.
2006, 45, 5991 – 5994; Angew. Chem. 2006, 118, 6137 – 6140; b) X.
Linghu, J. J. Kennedy-Smith, F. D. Toste, Angew. Chem. Int. Ed.
2007, 46, 7671 – 7673; Angew. Chem. 2007, 119, 7815 – 7817; c) G.
Bellavance, L. Barriault, Angew. Chem. Int. Ed. 2014, 53, 6701 –
6704; Angew. Chem. 2014, 126, 6819 – 6822.
rotation: [a]2D8 = À6.88 (c = 0.70, CHCl3); (lit. [a]2D2 = À108 (c =
0.07, CHCl3)).[9]
.
[19] CCDC 1454956 (6), CCDC 1454957 (21) and CCDC 1454958
(23) contain the supplementary crystallographic data. These data
can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
[20] See the Supporting Information for more details.
[21] Similarly, the cis addition was also favored for the pyrrolidine-
promoted process. See the Supporting Information for more
details.
[22] a) M. W. Lodewyk, M. R. Siebert, D. J. Tantillo, Chem. Rev.
2012, 112, 1839 – 1862; some recent examples: b) K. N. White, T.
Amagata, A. G. Oliver, K. Tenney, P. J. Wenzel, P. Crews, J. Org.
Chem. 2008, 73, 8719 – 8722; c) G. Hu, K. Liu, L. J. Williams,
Org. Lett. 2008, 10, 5493 – 5496; d) Y. Li, RSC Adv. 2015, 5,
36858 – 36864.
[15] Reviews on the application of gold catalysis to the synthesis of
natural products: a) A. Fürstner, Chem. Soc. Rev. 2009, 38,
3208 – 3221; b) M. Rudolph, A. S. K.; Hashmi, Chem. Soc. Rev.
2012, 41, 2448 – 2462; Hashmi, Chem. Soc. Rev. 2012, 41, 2448 –
2462; c) A. Fürstner, Acc. Chem. Res. 2014, 47, 925 – 938; d) Y.
Zhang, T.; Luo, Z. Yang, Nat. Prod. Rep. 2014, 31, 489 – 503; Luo,
Z. Yang, Nat. Prod. Rep. 2014, 31, 489 – 503; e) D. Pflästerer,
A. S. K. Hashmi, Chem. Soc. Rev. 2016, 45, 1331 – 1367.
[16] a) Procedure according to: G. Koza, C. Theunissen, J. R.
Al Dulayymi, M. S. Baird, Tetrahedron 2009, 65, 10214 – 10229;
b) Spectral data and optical rotation in accordance with those
previously reported for (R,R)-10: A. Kramer, H. Pfander, Helv.
Chim. Acta 1982, 65, 293 – 301.
[17] For example: a) S. Kim, I. S. Kee, Y. H. Park, J. H. Park, Synlett
1991, 183 – 184; b) W. H. Kim, A. R. Angeles, J. H. Lee, S. J.
Danishefsky, Tetrahedron Lett. 2009, 50, 6440 – 6441.
Received: February 22, 2016
Published online: April 27, 2016
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