Total synthesis of the biscarbazole alkaloids murrafolinea a-d by a domino sonogashira coupling/claisen rearrangement/electrocyclization reaction

Article abstract of DOI:10.1002/anie.201305993

Why take things one step at a time? Aryl-pyran-linked biscarbazole alkaloids of the murrafoline group (see crystal structure of murrafolinea A; dark gray: C, red: O, blue: N) were accessed readily by a novel domino reaction sequence involving Sonogashira

Full text of DOI:10.1002/anie.201305993

Angewandte
Chemie
DOI: 10.1002/anie.201305993
Natural Products
Total Synthesis of the Biscarbazole Alkaloids Murrafoline A–D by
a Domino Sonogashira Coupling/Claisen Rearrangement/
Electrocyclization Reaction**
V. Pavan Kumar, Konstanze K. Gruner, Olga Kataeva, and Hans-Joachim Knçlker*
Carbazole alkaloids continue to attract strong interest
because of their structural variety and promising pharmaco-
logical activities.[1] Besides their useful biological profile,
biscarbazole alkaloids have synthetically challenging struc-
tures.[1,2] In 1983, Furukawa and co-workers described the
isolation of murrafoline A (1) from the root bark of the
Chinese medicinal plant Murraya euchrestifolia (Scheme 1).[3]
Murrafoline A (1) occurs in nature in racemic form. Its
relative configuration was confirmed by X-ray crystal-struc-
ture analysis.[3] In the following decade, Furukawa and co-
workers isolated further aryl–pyran-linked biscarbazole alka-
loids from the same natural source: murrafoline B (2), C (3),
and D (4), which were all obtained as racemates.[4,5] The
characteristic structural feature of these alkaloids is a dihy-
drogirinimbine moiety (the structure of girinimbine (5) is
shown in Scheme 2), which is attached at the C4’ atom of the
Scheme 2. Structures of girinimbine (5), cyclomahanimbine (curryanin,
murrayazolidine; 6), and murrayafoline A (7).
pyran ring to a second carbazole framework. In the case of
murrafoline A (1), the dihydrogirinimbine moiety is attached
to C8 of the carbazole nucleus of cyclomahanimbine (6), in
murrafoline B (2) and D (4) to C8 and C6, respectively, of the
carbazole nucleus of murrayafoline A (7), and in murrafoli-
ne C (3) to C8 of the carbazole nucleus of girinimbine (5). All
three monomeric carbazole units present in murrafolines A–
D (1–4) have also been isolated from M. euchrestifolia: the
pyrano[3,2-a]carbazole girinimbine (5), the cyclized mono-
terpenoid pyrano[3,2-a]carbazole cyclomahanimbine (6), and
the 1-oxygenated tricyclic carbazole alkaloid murrayafoli-
ne A (7) (Scheme 2).[6]
Scheme 1. Structures of the murrafolines A–D (1–4).
By using organometallic chemistry for carbazole con-
struction, we previously developed synthetic routes to giri-
nimbine (5),[7,8] cyclomahanimbine (6),[8] and murrayafoli-
ne A (7).[9] A recent approach to girinimbine (5) relies on the
[*] Dr. V. P. Kumar, Dr. K. K. Gruner, Dr. O. Kataeva,
Prof. Dr. H.-J. Knçlker
2-propargyloxycarbazole 10 as
a crucial intermediate
(Scheme 3).[8] On heating in toluene at reflux, a reaction
sequence involving a Claisen rearrangement to 10a, enoliza-
tion and a 1,5-H shift to give 10b, and finally electrocyclic ring
closure led to 5.[10]
Department of Chemistry, Technische Universitꢀt Dresden
Bergstrasse 66, 01069 Dresden (Germany)
E-mail: hans-joachim.knoelker@tu-dresden.de
Homepage: http://www.chm.tu-dresden.de/oc2/
[**] Part 110 of “Transition Metals in Organic Synthesis”; for part 109,
see: Ref. [8]. We are grateful to the Alexander von Humboldt
Foundation (fellowship to V.P.K.) and the Deutsche Forschungsge-
meinschaft (grant KN 240/16-1) for financial support. We thank
Regina Czerwonka and Nils Richter for experimental support.
Herein, we describe the first total synthesis of the
murrafolines A–D by a novel domino reaction sequence.
Domino reactions have proven to be ideal for efficiently
generating high molecular complexity in one-pot processes
because multistep transformations are executed without
intermediate workup.[11] Therefore, we aimed to construct
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201305993.
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(see Scheme 3) and thus directly provide the aryl–pyran-
linked biscarbazole framework in a domino reaction.
Owing to their substitution pattern, we projected the
synthesis of murrafoline A (1) and murrafoline C (3) by the
same approach (Scheme 4). We assembled the carbazole
framework by our palladium-catalyzed synthesis:[13,14] Buch-
wald–Hartwig coupling of the aryl bromide 11 and aniline 12
with DavePhos as the ligand,[15] followed by palladium(II)-
catalyzed oxidative cyclization, afforded the desired 2,8-
dioxygenated carbazole 13, which was desilylated and con-
verted into the carbazol-8-yl triflate 14. Sonogashira coupling
of 14 and the 2-propargyloxycarbazole 10 to give the aryl
propargyl ether 15 was immediately followed by the sequence
of Claisen rearrangement, enolization, 1,5-H shift, and
electrocyclic ring closure to provide the biscarbazole 16.
This one-pot process was promoted by the addition of xylene
and heating at reflux after completion of the Sonogashira
coupling (see the Experimental Section). Hydrogenation of
the double bond in the pyran ring occurred with concomitant
cleavage of the benzyl ether to afford compound 17. The
formation of a dimethylpyran ring at the hydroxycarbazole
unit of 17 by the Lewis acid promoted annulation of
prenal[8,16] afforded murrafoline C (3).[17] Alternatively,
a Lewis acid promoted reaction of 17 with citral provided
compound 18, which on proton-catalyzed cycloisomerization
Scheme 3. Synthesis of girinimbine (5) via the 2-propargyloxycarbazole
10: a) 1. PhI, Pd(OAc)2 (5 mol%), SPhos (10 mol%), Cs2CO3, toluene,
1008C, 26 h; 2. Pd(OAc)2 (5 mol%), K2CO3 (5 mol%), pivalic acid, air,
1008C, 24 h; 3. BBr3, CH2Cl2, ꢀ788C!RT, 15.5 h (85%); b) methyl 2-
methylbut-3-yn-2-yl carbonate (1.5 equiv), Cs2CO3 (2 equiv), CuI
(0.5 mol%), acetonitrile, RT, 24 h (65%); c) toluene, reflux, 29 h
(55%). SPhos=2-dicyclohexylphosphanyl-2’,6’-dimethoxybiphenyl.
the characteristic aryl–pyran linkage of the murrafolines at
the stage of intermediate 10 by a palladium-catalyzed
Sonogashira coupling to the terminal alkyne.[12] This process
could then perhaps be combined in a one-pot reaction with
the sequence of steps leading to annulation of the pyran ring
Scheme 4. Synthesis of murrafoline A (1) and murrafoline C (3): a) 12 (1.5 equiv), [Pd2(dba)3] (6 mol%), DavePhos (12 mol%), NaOtBu
(1.2 equiv), toluene, reflux, 24 h (98%); b) Pd(OAc)2 (20 mol%), K2CO3 (20 mol%), pivalic acid, 858C, 20 h (85%); c) TBAF (1.5 equiv), THF,
08C!RT, 2 h (100%); d) Tf2O (1.2 equiv), pyridine, 08C!RT, 12 h (74%); e) 1. 10 (1.3 equiv), [Pd(PPh3)4] (10 mol%), CuI (0.5 mol%), piperidine,
RT, 20 h; 2. xylene, reflux, 1.5 h (61%); f) 30% Pd/C, H2, EtOAc, RT, 2 d (97%); g) prenal (2 equiv), Ti(OiPr)4 (4 equiv), ꢀ788C!RT, 22 h (75%);
h) citral (2 equiv), Ti(OiPr)4 (4 equiv), ꢀ788C!RT, 20 h (89%); i) camphorsulfonic acid (2 equiv), toluene, RT, 7 d (77%; 1/epi-1 1:1). Bn=benzyl,
DavePhos=2-(dicyclohexylphosphanyl)-2’-(N,N-dimethylamino)biphenyl, dba=dibenzylideneacetone, TBAF=tetrabutylammonium fluoride,
Tf =trifluoromethanesulfonyl, TIPS=triisopropylsilyl.
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led to murrafoline A (1) and its non-natural diastereoisomer
epi-1 (77% yield, 1:1 mixture). The two diastereoisomers
were separated by HPLC[18] and fully characterized,[17] and
the structure of the natural product was confirmed by X-ray
crystallographic analysis (Figure 1).[19]
We then extended our methodology to the synthesis of
murrafoline B (2; Scheme 5). The coupling of 11 with aniline
19 and subsequent oxidative cyclization led to the carbazole
20, which after removal of the silyl group was converted into
the triflate 21. The treatment of 21 with the 2-propargyl-
oxycarbazole 10 directly provided the biscarbazole 22 through
the domino Sonogashira coupling/Claisen rearrangement/
electrocyclization sequence. Reduction with lithium alumi-
num hydride followed by catalytic hydrogenation of the pyran
double bond gave murrafoline B (2).[17]
For the synthesis of murrafoline D (4), we used mukonine
(23) as the starting material (Scheme 6). Mukonine (23) can
be prepared either by a previously reported iron-mediated or
Scheme 6. Synthesis of murrafoline D (4): a) KI (1.4 equiv), KIO3
(1.5 equiv), AcOH, 558C, 3 h (100%); b) 1. 10 (1.3 equiv), [Pd(PPh3)4]
(10 mol%), CuI (0.5 mol%), piperidine, RT, 12 h; 2. xylene, reflux, 2 h
(89%); c) LiAlH4 (4 equiv), CH2Cl2/Et2O (1:1), RT, 5 h (78%);
d) 30% Pd/C, H2, EtOAc, RT, 16 h (92%).
Figure 1. Molecular structure of murrafoline A (1) in the crystal
(ORTEP plot showing thermal ellipsoids at the 50% probability level).
by the palladium-catalyzed carbazole synthesis.[20,21] By our
improved route based on palladium catalysis, mukonine (23)
was prepared in two steps and 91% overall yield.[21c] Electro-
philic iodination of 23 afforded 6-iodomukonine (24), which
underwent a domino reaction with the 2-propargyloxycarba-
zole 10 to afford the biscarbazole 25 in excellent yield (89%).
The structure of 25 was confirmed by X-ray crystal-structure
determination (Figure 2).[22] Reduction of the ester to
Scheme 5. Synthesis of murrafoline B (2): a) 11 (1.1 equiv), [Pd2(dba)3]
(6 mol%), SPhos (12 mol%), Cs2CO3 (1.4 equiv), toluene, reflux, 24 h
(98%); b) Pd(OAc)2 (1.1 equiv), AcOH, reflux, 24 h (67%); c) TBAF
(1.5 equiv), THF, 0.5 h, 08C!RT (100%); d) Tf2O (1.2 equiv), pyridine,
ꢀ158C!RT, 2 h (90%); e) 1. 10 (1.3 equiv), [Pd(PPh3)4] (10 mol%),
CuI (0.5 mol%), piperidine, RT, 2 d; 2. xylene, reflux, 2 h (39%);
f) LiAlH4 (4 equiv), CH2Cl2/Et2O (1:1), RT, 6 h (63%); g) 30% Pd/C,
H2, EtOAc, RT, 4 d (95%).
Figure 2. Molecular structure of the biscarbazole 25 in the crystal
(ORTEP plot showing thermal ellipsoids at the 50% probability level).
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d) H.-J. Knçlker, Curr. Org. Synth. 2004, 1, 309; e) H.-J. Knçlker,
K. R. Reddy in The Alkaloids, Vol. 65 (Ed.: G. A. Cordell),
Academic Press, Amsterdam, 2008, p. 1; f) A. W. Schmidt, K. R.
Reddy, H.-J. Knçlker, Chem. Rev. 2012, 112, 3193.
a methyl group, followed by hydrogenation of the pyran ring,
completed this total synthesis and provided murrafoline D (4)
in four steps and 62% overall yield from mukonine (23).[17]
In conclusion, our present results emphasize that the
reaction sequence of Sonogashira coupling, Claisen rear-
rangement, and electrocyclic ring closure, which can be
performed as one-pot process, is ideal for the assembly of the
framework of aryl–pyran-linked biscarbazole alkaloids of the
murrafoline type. Thus, a domino reaction of the 2-propargyl-
oxycarbazole 10 with the appropriately functionalized carba-
zolyl triflate 14 or 21 or iodocarbazole 24 provided direct
routes to murrafolines A–D (1–4). Further elaboration of this
synthetic approach and an investigation of the biological
activity of the murrafolines are in progress.
[2] a) H. Furukawa, Trends Heterocycl. Chem. 1993, 3, 185; b) S.
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[5] H. Furukawa, C. Ito, T.-S. Wu, A. T. McPhail, Chem. Pharm.
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[6] H. Furukawa, T.-S. Wu, T. Ohta, C.-S. Kuoh, Chem. Pharm. Bull.
1985, 33, 4132.
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3902; c) K. K. Gruner, T. Hopfmann, K. Matsumoto, A. Jꢀger, T.
Katsuki, H.-J. Knçlker, Org. Biomol. Chem. 2011, 9, 2057.
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[10] a) I. Iwai, J. Ide, Chem. Pharm. Bull. 1962, 10, 926; b) I. Iwai, J.
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c) L. F. Tietze, G. Brasche, K. Gericke, Domino Reactions in
Organic Synthesis, Wiley-VCH, Weinheim, 2006; d) L. F. Tietze,
S. G. Stewart, A. Dꢁfert in Modern Tools for the Synthesis of
Complex Bioactive Molecules (Eds.: J. Cossy, S. Arseniyadis),
Wiley, Hoboken, 2012, p. 271.
[12] a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.
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2007, 107, 874.
[13] a) H.-J. Knçlker, N. OꢃSullivan, Tetrahedron 1994, 50, 10893;
b) H.-J. Knçlker, K. R. Reddy, Heterocycles 2003, 60, 1049;
c) M. P. Krahl, A. Jꢀger, T. Krause, H.-J. Knçlker, Org. Biomol.
Chem. 2006, 4, 3215; d) R. Forke, M. P. Krahl, T. Krause, G.
Schlechtingen, H.-J. Knçlker, Synlett 2007, 268; e) C. Bçrger, H.-
J. Knçlker, Synlett 2008, 1698; f) R. Forke, A. Jꢀger, H.-J.
Knçlker, Org. Biomol. Chem. 2008, 6, 2481; g) R. Forke, M. P.
Krahl, F. Dꢀbritz, A. Jꢀger, H.-J. Knçlker, Synlett 2008, 1870;
h) T. Gensch, M. Rçnnefahrt, R. Czerwonka, A. Jꢀger, O.
Kataeva, I. Bauer, H.-J. Knçlker, Chem. Eur. J. 2012, 18, 770.
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115; b) H.-J. Knçlker, Chem. Lett. 2009, 38, 8; c) R. Forke, K. K.
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S. Richter, G. Tsiavaliaris, R. Fedorov, D. J. Manstein, H. O.
Gutzeit, H.-J. Knçlker, Pure Appl. Chem. 2010, 82, 1975; d) I.
Bauer, H.-J. Knçlker, Top. Curr. Chem. 2012, 309, 203.
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[16] G. Sartori, G. Casiraghi, L. Bolzoni, G. Casnati, J. Org. Chem.
1979, 44, 803.
Experimental Section
Synthesis of 16: The 2-propargyloxycarbazole 10 (196 mg, 746 mmol),
[Pd(PPh3)4] (66 mg, 57.4 mmol), and CuI (0.54 mg, 2.8 mmol) were
added to a solution of the carbazol-8-yl triflate 14 (250 mg, 574 mmol)
in piperidine (5 mL), and the reaction mixture was stirred for 20 h at
room temperature under an argon atmosphere. Xylene (10 mL) was
then added, and the mixture was heated at reflux for 90 min, then
poured into a saturated aqueous solution of NH4Cl. The resulting
mixture was extracted three times with CH2Cl2, the combined organic
layers were washed with brine and dried over Na2SO4, and the solvent
was evaporated. Purification of the crude product by flash chroma-
tography on silica gel (EtOAc/pentane, 9:1) provided the biscarba-
zole 16 (192 mg, 61%) and 14 (35 mg, 14%). 16: colorless crystals;
m.p.: 1588C; UV (MeOH): l = 217 (sh), 238, 278 (sh), 288, 304 (sh),
337 (sh), 358 (sh) nm; fluorescence (MeOH): lex = 288 nm, lem
361 nm; IR (KBr): n˜ = 3443, 2919, 2849, 2030, 1631, 1606, 1578,
1492, 1415, 1286, 1199, 1142, 1049, 1026, 817, 739, 692, 620 cmꢀ1
=
;
1H NMR (500 MHz, [D6]acetone): d = 1.55 (m, 3H), 1.61 (m, 3H),
2.38 (s, 3H), 2.40 (s, 3H), 5.11 (s, 2H), 5.97 (s, 1H), 6.85 (d, J = 7.9 Hz,
1H), 6.91 (s, 1H), 6.98–7.06 (m, 2H), 7.23–7.26 (m, 2H), 7.29 (br t, J =
7.5 Hz, 1H), 7.36 (br t, J = 7.5 Hz, 2H), 7.46 (d, J = 7.1 Hz, 2H), 7.64
(br s, 1H), 7.83 (s, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 8.12 (dd,
J = 6.8, 2.4 Hz, 1H), 9.91 ppm (br s, 1H); 13C NMR (125 MHz,
[D6]acetone): d = 16.63 (CH3), 17.03 (CH3), 27.21 (CH3), 27.30
(CH3), 70.35 (CH2), 76.31 (C), 95.17 (CH), 106.42 (C), 111.31 (CH),
117.04 (C), 118.39 (C), 119.27 (C), 119.50 (CH), 119.63 (CH), 119.70
(C), 119.95 (CH), 120.05 (CH), 122.16 (CH), 122.37 (CH), 122.42 (C),
123.53 (C), 124.76 (C), 124.82 (CH), 124.93 (CH), 127.92 (2CH),
128.40 (CH), 129.22 (2CH), 130.78 (CH), 130.94 (C), 135.58 (C),
138.56 (C), 138.64 (C), 140.19 (C), 140.93 (C), 151.63 (C), 157.30 ppm
(C); ESI-MS: m/z 549.3 [M+H]+, 566.2 [M+NH4]+; elemental
analysis: calcd (%) for C38H32N2O2: C 83.18, H 5.88, N 5.11; found:
C 82.98, H 5.57, N 5.24.
Received: July 10, 2013
Revised: August 14, 2013
Published online: && &&, &&&&
ꢀ
Keywords: alkaloids · C H bond activation · natural products ·
palladium · X-ray diffraction
.
[17] Murrafoline A (1): colorless crystals; m.p.: 2678C (lit.:[3,5] 260–
2628C); elemental analysis: calcd (%) for C41H42N2O2: C 82.79,
H 7.12, N 4.71; found: C 82.40, H 7.97, N 4.32. epi-Murrafoline A
(epi-1): colorless crystals; m.p.: 2258C. Murrafoline B (2): color-
less crystals; m.p.: 2288C (lit.:[4,5] 234–2378C); elemental anal-
ysis: calcd (%) for C32H30N2O2: C 80.98, H 6.37, N 5.90; found: C
81.00, H 6.74, N 5.70. Murrafoline C (3): colorless crystals, m.p.:
2258C (lit.:[4,5] colorless oil); elemental analysis: calcd (%) for
[1] For reviews, see: a) D. P. Chakraborty, S. Roy in Progress in the
Chemistry of Organic Natural Products, Vol. 57 (Eds.: W. Herz,
H. Grisebach, G. W. Kirby, W. Steglich, C. Tamm), Springer,
Wien, 1991, p. 71; b) D. P. Chakraborty in The Alkaloids, Vol. 44
(Ed.: G. A. Cordell), Academic Press, New York, 1993, p. 257;
c) H.-J. Knçlker, K. R. Reddy, Chem. Rev. 2002, 102, 4303;
4
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C36H34N2O2: C 82.10, H 6.51, N 5.32; found: C 81.38, H 7.14, N
5.41. Murrafoline D (4): colorless crystals; m.p.: 2748C (lit.:[5]
amorphous powder, no m.p. given); elemental analysis: calcd
(%) for C32H30N2O2: C 80.98, H 6.37, N 5.90; found: C 80.83, H
[20] a) H.-J. Knçlker, M. Bauermeister, J. Chem. Soc. Chem.
Commun. 1990, 664; b) H.-J. Knçlker, M. Bauermeister, Tetra-
hedron 1993, 49, 11221; c) H.-J. Knçlker, M. Wolpert, Tetrahe-
dron Lett. 1997, 38, 533; d) H.-J. Knçlker, M. Wolpert, Tetrahe-
dron 2003, 59, 5317.
6.69,
N
5.36. For the 1H NMR (600 MHz) and 13C NMR
[21] a) M. P. Krahl, PhD thesis, TU Dresden, 2006; b) B. Liꢆgault, D.
Lee, M. P. Huestis, D. R. Stuart, K. Fagnou, J. Org. Chem. 2008,
73, 5022; c) C. Bçrger, M. P. Krahl, M. Gruner, O. Kataeva, H.-J.
Knçlker, Org. Biomol. Chem. 2012, 10, 5189.
(150 MHz) spectra of murrafolines A–D (1–4), see the Support-
ing Information.
[18] Chiral phase: Nucleocel d-RP (Macherey–Nagel), column
dimensions: 250 ꢄ 2.1 mm2, temperature: 208C, eluent: MeCN/
[22] Crystallographic data for 25: C34H32Cl2N2O5, M = 619.52 gmolꢀ1
,
H2O (85:15), flow rate: 12 mLminꢀ1
.
crystal size: 0.38 ꢄ 0.25 ꢄ 0.15 mm3, monoclinic, space group C2/
c, a = 35.976(3), b = 14.475(1), c = 13.004(1) ꢅ, V= 6520.6(9) ꢅ3,
Z = 8, 1calcd = 1.262 gcmꢀ3, m = 0.242 mmꢀ1, l = 0.71073 ꢅ, T=
198(2) K, q range: 1.18 – 26.008, reflections collected: 63047,
independent: 6286 (Rint = 0.0963), 446 parameters. The structure
was solved by direct methods and refined by full-matrix least-
squares on F2; final R indices [I > 2s(I)]: R1 = 0.0729, wR2 =
0.02073; maximal residual electron density: 0.765 eꢅꢀ3. The
crystal contains a void filled with disordered solvent molecules
(1719 ꢅ3 per cell unit), which were modeled by dichloromethane
and water molecules. CCDC 948511 contains the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[19] Crystallographic data for 1: C41H42N2O2, M = 594.77 gmolꢀ1
,
crystal size: 0.43 ꢄ 0.26 ꢄ 0.25 mm3, monoclinic, space group P21/
c, a = 11.880(1), b = 12.416(1), c = 21.633(2) ꢅ, b = 93.801(7)8,
V= 3183.9(5) ꢅ3, Z = 4, 1calcd = 1.241 gcmꢀ3, m = 0.076 mmꢀ1, l =
0.71073 ꢅ, T= 198(2) K, q range: 3.10 – 27.008, reflections col-
lected: 32306, independent: 6902 (Rint = 0.0516), 412 parameters.
The structure was solved by direct methods and refined by full-
matrix least-squares on F2; final R indices [I > 2s(I)]: R1 =
0.0474, wR2 = 0.1077; maximal residual electron density:
0.199 eꢅꢀ3. CCDC 948510 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Natural Products
Why take things one step at a time? Aryl–
pyran-linked biscarbazole alkaloids of the
murrafoline group (see crystal structure
of murrafoline A) were accessed readily
by a novel domino reaction sequence
involving Sonogashira coupling, a Claisen
rearrangement, and electrocyclization.
The one-pot procedure enables the
straightforward synthesis of these struc-
turally challenging alkaloids in only a few
steps.
V. P. Kumar, K. K. Gruner, O. Kataeva,
H.-J. Knçlker*
&&&& — &&&&
Total Synthesis of the Biscarbazole
Alkaloids Murrafoline A–D by a Domino
Sonogashira Coupling/Claisen
Rearrangement/Electrocyclization
Reaction
6
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!