Biomimetic Collective Total Synthesis of Bioactive Carbazole Alkaloids Indizoline, Mafaicheenamine A, Claulamine A, Claulansine A, and the Proposed Claulamine e

Article abstract of DOI:10.1021/acs.joc.6b00702

The common precursor 1-methoxy-2-prenyl-3-carbomethoxycarbazole was synthesized from dimethyl indolylmethylenesuccinate in four steps. Well-planned reductive and/or oxidative transformations and intramolecular cyclizations were performed on a pivotal common precursor to accomplish collective first total synthesis of titled natural products and proposed claulamine E. Burgess reagent induced formation of kinetically controlled product claulamine A, and intramolecular cyclizations to form bicyclic claulansine A were the key reactions. An alternatively attempted synthesis failed to provide the structural isomer of proposed claulamine E.

Full text of DOI:10.1021/acs.joc.6b00702

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Note
Biomimetic Collective Total Synthesis of Bioactive
Carbazole Alkaloids Indizoline, Mafaicheenamine A,
Claulamine A, Claulansine A and the Proposed Claulamine E
Shivaji B. Markad, and Narshinha P. Argade
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00702 • Publication Date (Web): 26 May 2016
Downloaded from http://pubs.acs.org on May 30, 2016
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Biomimetic Collective Total Synthesis of Bioactive Carbazole Alkaloids Indizoline,
Mafaicheenamine A, Claulamine A, Claulansine A and the Proposed Claulamine E
Shivaji B. Markad and Narshinha P. Argade*
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Division of Organic Chemistry, National Chemical Laboratory (CSIR), Pune 411 008, India
np.argade@ncl.res.in
ABSTRACT: The common precursor 1-methoxy-2-prenyl-3-carbomethoxycarbazole was synthesized
from dimethyl indolylmethylenesuccinate in four steps. Well planned reductive and/or oxidative
transformations and intramolecular cyclizations were performed on a pivotal common precursor to
accomplish collective first total synthesis of titled natural products and the proposed claulamine E.
Burgess reagent induced formation of kinetically controlled product claulamine A and intramolecular
cyclizations to form bicyclic claulansine A were the key reactions. An alternatively attempted
synthesis failed to provide the structural isomer of proposed claulamine E.
The carbazoles are an important class of alkaloids and a large number of them have been isolated from
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plant, animal, microbial and marine origin. Carbazoles display a wide range of biological activities
and also find applications in electroluminescent materials owing to their electrical and thermal
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properties. The indizoline, mafaicheenamine A, claulamine A, claulansine A and claulamine E have
been recently isolated from Clausena lansium and they exhibit potent anti-inflammatory,
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neuroprotective and antitumor activities against human cancer cell lines (Figure 1).
In the synthesis
of carbazoles, regioselective installation of appropriate substituents on the eight different available
1‒3,12
sites in the aromatic ring systems is a challenging task.
Total synthesis of bioactive natural
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products has very successfully completed ample glorious achievements. A collective total synthesis of
bioactive natural products is of contemporary interest from the strategic flexibility and dedicated SAR
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studies point of view.
The synthesis of structurally interesting and biologically important selected
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target compounds, however, merits further investigation. On the basis of retrosynthetic analysis we
reasoned that the combination of readily available N-boc-protected-3-formylindole, dimethyl maleate
and prenyl bromide would constitute a diversity oriented convergent access to these important
carbazole based natural products. In the continuation of our studies on cyclic anhydrides and their
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conversion to bioactive natural products
we herein report the collective total synthesis of target
(Schemes 1–3).
compounds
ꢀ
Figure 1. Representative bioactive carbazole alkaloids and their concise retrosynthetic analysis.
The Wittig adduct dimethyl (E)-2-((1-(tert-butoxycarbonyl)-1H-indol-3-yl)methylene)succinate
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(1) on treatment with NaHMDS/prenyl bromide delivered the expected mono-prenylated product 2
in 71% yield. Diester 2 on selective base-induced hydrolysis of the more reactive saturated ester
moiety exclusively provided the desired carboxylic acid 3 in 89% yield (Scheme 1). Both the N-boc-
deprotection and regioselective ester hydrolysis took place in one-pot. The witnessed in situ N-boc-
deprotection under basic conditions was plausibly due to the conjugation of nitrogen lone pair with
α,β,γ,δ-unsaturated ester moiety. Acid 3 on triphosgene induced intramolecular acylation followed by
O-methylation of the formed phenol 4 resulted in the suitably trisubstituted requisite carbazole 5 in
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8% yield over two steps. An appropriately designed 20-carbon-bearing versatile single precursor 5
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can then be neatly tailored to each of the five target compounds via various reductive and/or oxidative
regio- and stereoselective intramolecular cyclization pathways.
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Scheme 1. A Facile Synthesis of Common Precursor 1-Methoxy-2-prenyl-3-carbomethoxycarbazole
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Scheme 2. Concise and Efficient Collective Total Synthesis of Bioactive Carbazole Alkaloids
The potential precursor carbazole 5 on DIBAL-H reduction of carbomethoxy unit provided alcohol
6 in 88% yield; which on PCC-oxidation furnished the first natural product indizoline (7) in 95% yield
(
Scheme 2). The two-step transformation of natural sample of indizoline (7) to yet another natural
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product claulansine G (8) is known but in very low overall yield, plausibly due to the poor stability
and inherent polymerization issues. The prenyl group bearing carbazole 6 on treatment with m-CPBA
at ‒10 °C resulted into the expected epoxide 9 in 72% yield in 15 minutes. Epoxide 9 was highly prone
for further intramolecular ring closure and hence it was characterized without purification. The
isolated epoxide 9 on simple stirring in acetone at room temperature underwent regioselective
intramolecular cyclization with a cleavage of the oxirane moiety to deliver the desired product 10 in
96% yield. The above mentioned m-CPBA epoxidation of carbazole 6 at room temperature directly
furnished the planned product 10 in 83% yield. Unfortunately, the obtained analytical and spectral data
for compound 10 was not in agreement with reported data for the natural product claulamine E (Table
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). Finally, the structural assignment of synthetic product 10 was unequivocally confirmed by X-ray
crystallography. Hence what we have accomplished is the total synthesis of the structure initially
proposed as claulamine E (10) and an appropriate revision in structural assignment for the natural
product is therefore recommended. In principle, several regioisomeric unknown structures are possible
and the X-ray crystallographic analysis of the natural product would be most appropriate for the proper
structural assignment.
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Table 1. NMR Data of Natural and Proposed Claulamine E in Acetone-d
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Natural (Ref. 11)
Proposed 10
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Hꢀ(400ꢀMHz)ꢀ Cꢀ(100ꢀMHz)ꢀ Hꢀꢀ(500ꢀMHz)ꢀꢀꢀ Cꢀ(125ꢀMHz)ꢀ
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1.32ꢀ(s,ꢀ3H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ19.7ꢀ 1.28ꢀ(s,ꢀ3H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ24.2ꢀ
1.36ꢀ(s,ꢀ3H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ27.6ꢀ 1.29ꢀ(s,ꢀ3H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ25.7ꢀ
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.29ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ31.3ꢀ 2.80–2.90ꢀ(m,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ26.4ꢀ
.39ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ61.4ꢀ 3.10ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ60.4ꢀ
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ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ66.5ꢀ 3.44ꢀ(brꢀs,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ70.0ꢀ
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.55ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ75.7ꢀ 3.49ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ72.0ꢀ
.92ꢀ(s,ꢀ3H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ79.6ꢀ 3.96ꢀ(s,ꢀ3H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ82.7ꢀ
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.60ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ111.9ꢀ 4.92ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ111.7ꢀ
4.84ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ115.7ꢀ 5.05ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ112.0ꢀ
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.15ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ119.7ꢀ 7.14ꢀ(t,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ119.7ꢀ
.35ꢀ(dd,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ120.7ꢀ 7.36ꢀ(t,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ120.9ꢀ
7.51ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ123.4ꢀ 7.50ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ124.35ꢀ
.66ꢀ(s,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ124.4ꢀ 7.55ꢀ(s,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ124.43ꢀ
.03ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ126.1ꢀ 8.02ꢀ(d,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ124.7ꢀ
10.39ꢀ(brꢀs,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ128.1ꢀ 10.31ꢀ(brꢀs,ꢀ1H)ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ126.5ꢀ
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ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ134.6ꢀ ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ132.8ꢀ
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The common precursor carbazole 5 on osmium tetraoxide induced cis-dihydroxylation directly
delivered the natural product mafaicheenamine A (11) in 86% yield via an anticipated in situ
regioselective lactonization (Scheme 2). The reactions of mafaicheenamine A (11) with
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2 2 5 3
SOCl /P O /POCl were not selective and resulted in a mixture of products. However, the reaction of
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mafaicheenamine A (11) with the Burgess reagent was completely selective and provided the
kinetically controlled desired natural product claulamine A (12) in 74% yield. We propose that both
the steric bulk and higher reactivity of Burgess reagent are responsible for the exclusive formation of
kinetically controlled product 12. Mafaicheenamine A (11) on DIBAL-H reduction at ‒78 to 25 °C
formed the corresponding triol 13 in 79% yield in 4 hours. In a cascade reaction, the triol 13 on
treatment with PCC directly yielded yet another natural product claulansine A (14) in 70% yield.
Mechanistically, the stepwise selective oxidation of the primary alcohol to the corresponding
aldehyde, an in situ cyclic trans-hemiacetal formation with the secondary alcohol and an associated
instantaneous diastereoselective intramolecular dehydrative ring closure utilizing the tertiary alcohol
took place to form the desired product 14 in one pot. Similarly, an osmium tetraoxide induced cis-
dihydroxylation of indizoline (7) at room temperature also directly furnished the claulansine A (14) in
good yield. The temperature controlled DIBAL-H reduction of mafaicheenamine A (11) at ‒78 °C also
directly delivered the claulansine A (14) in 77% yield in 3 hours. During the DIBAL-H reductions, the
intermediate lactol was fairly stable at ‒78 °C and further underwent a concomitant diastereoselectve
intramolecular dehydrative cyclization to provide claulansine A (14). Either the DIBAL-H reduction
of 11 directly forms the trans-hemiacetal intermediate or the formed cis-hemiacetal could be
rearranging to the trans-hemiacetal via ring-chain tautomerism making the formation of corresponding
desired acetal 14 feasible. Triol 13 on treatment with p-TSA again provided the proposed claulamine E
(
10) in 81% yield via protonation of benzylic alcohol followed by the regioselective intramolecular
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dehydrative cyclization. The obtained analytical and spectral data for all target compounds except for
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claulamine E were in complete agreement for the reported data.
In order to address the inconsistencies between the structure of proposed claulamine E and
compound 10, we propose a revised structure for claulamine E. On the basis of structural features of
all the carbazoles depicted in Figure 1, we presumed that the assigned positions of ‒OMe group and
cyclic benzyl ether unit in the proposed claulamine E are accurate. Therefore alternatively the prenyl
moiety could be at the para-position of methoxy group. Accordingly, we planned the synthesis of
corresponding isomeric compound 18 as a potential revised structure of claulamine E (Scheme 3).
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8
9
0
2
7
Thus the desired precursor 15 was synthesized using known literature procedures. The compound 15
on DIBAL-H reduction resulted in benzylic alcohol 16 in 87% yield, which on treatment with m-
CPBA delivered compound 17 in 81% yield. The epoxide 17 remained unreacted in refluxing acetone,
while it decomposed in the presence of 2 N HCl in chloroform at ‒30 °C. Unfortunately, epoxide 17
failed to undergo intramolecular cyclization to provide the desired regioisomeric product 18.
ꢀ
Scheme 3. Synthesis of Regioisomer of the Proposed Claulamine E
In summary, we have demonstrated a concise and efficient access to accomplish a biogenetic
collective total synthesis of carbazole alkaloids from readily available simple starting materials. The
involved different types of intramolecular cyclizations with the generation of new carbon‒oxygen
bonds selectively leading to those natural products are noteworthy from both basic chemistry and
applications point of view. More specifically, remarkable cascade reaction has been demonstrated in
the synthesis of claulansine A by taking the advantage of reactivity difference in three different types
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of alcohol units. We have accomplished an efficient total synthesis of the proposed structure of
claulamine E and regioisomeric revision in structural assignment of natural product is necessary.
Sharpless asymmetric dihydroxylation reactions will provide access to the enantiomerically pure target
compounds and their antipodes. The present approach provides an avenue to natural and unnatural
carbazoles for SAR studies.
10
11
12
13
14
15
16
17
18
19
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EXPERIMENTAL SECTION
1
General Description. Melting points are uncorrected. The H NMR spectra were recorded on 200
MHz NMR, 400 MHz NMR and 500 MHz NMR spectrometers using TMS as an internal standard.
1
3
The C NMR spectra were recorded on 200 NMR (50 MHz), 400 NMR (100 MHz) and 500 NMR
(125 MHz) spectrometers. Mass spectra were taken on MS-TOF mass spectrometer. HRMS (ESI)
were taken on Orbitrap (quadrupole plus ion trap) and TOF mass analyzer. The IR spectra were
recorded on an FT-IR spectrometer. Commercially available starting materials and reagents were used.
Dimethyl
(E)-2-((1-(tert-Butoxycarbonyl)-1H-indol-3-yl)methylene)-3-(3-methylbut-2-en-1-
yl)succinate (2). To a stirred solution of compound 1 (10.00 g, 26.66 mmol) in dry THF (70 mL) was
dropwise added a solution of NaHMDS in THF (1 M, 53.3 mL, 53.33 mmol) at ‒78 °C under argon
atmosphere. The reaction mixture was stirred for 30 min and prenyl bromide (4.64 mL, 40.21 mmol)
was added dropwise. It was further stirred for 45 min at ‒78 °C and the reaction was quenched with
saturated aqueous NH
4
Cl. Solvent was removed in vacuo and the obtained residue was dissolved in
SO
EtOAc (300 mL). The organic layer was washed with water, brine and dried over Na
2
4
.
Concentration of organic layer in vacuo followed by silica gel (60‒120 mesh) column
chromatographic purification of the obtained residue using ethyl acetate‒petroleum ether (1:9) as an
1
eluent yielded pure 2 as thick oil (8.38 g, 71%). H NMR (CDCl
3
, 400 MHz) δ 1.58 (s, 3H), 1.59 (s,
3
H), 1.68 (s, 9H), 2.47–2.57 (m, 1H), 2.83–2.93 (m, 1H), 3.68 (s, 3H), 3.82 (s, 3H), 3.89 (dd, J = 8
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and 8 Hz, 1H), 5.06 (t, J = 8 Hz, 1H), 7.28 (t, J = 8 Hz, 1H), 7.36 (t, J = 8 Hz, 1H), 7.67 (d, J = 8 Hz,
1
3
1
2
1
3
H), 7.81 (s, 1H), 7.93 (s, 1H), 8.14 (d, J = 8 Hz, 1H); C NMR (CDCl , 100 MHz) δ 17.7, 25.6, 28.0,
8.4, 44.5, 51.8, 51.9, 84.3, 115.1, 115.3, 119.0, 121.1, 123.0, 124.8, 125.0, 129.9, 130.6, 131.7,
0
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9
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9
0
+
33.6, 134.9, 149.2, 166.9, 172.9; ESIMS (m/z) 464 [M+Na] ; HRMS (ESI) calcd for C25
H
31
O
6
NNa
1
−
464.2044, found 464.2036; IR (CHCl
3
) νmax 1736, 1636 cm .
(
E)-2-(1-(1H-Indol-3-yl)-3-methoxy-3-oxoprop-1-en-2-yl)-5-methylhex-4-enoic
Acid
(3).
To a solution of compound 2 (7.50 g, 17.00 mmol) in MeOH:H
2
O (3:1, 40 mL) was added KOH (2.09
g, 37.41 mmol) at 25 °C and the reaction mixture was stirred for 25 h. The reaction mixture was
concentrated in vacuo and obtained residue was acidified by 2 N HCl and extracted with ethyl acetate
2 4
(70 mL × 3). The combined extract was washed with water, brine and dried over Na SO . The organic
layer was concentrated in vacuo and obtained residue was purified by silica gel (60‒120 mesh) column
chromatography using ethyl acetate‒petroleum ether (8:2) as an eluent to yield acid 3 as a white solid
1
(4.94 g, 89%). Mp 188‒190 °C; H NMR (DMSO-d
6
, 200 MHz) δ 1.50 (s, 6H), 2.07– 2.55 (m, 1H),
2
.60–2.80 (m, 1H), 3.71 (s, 3H), 3.93 (dd, J = 10 and 6 Hz, 1H), 5.06 (t, J = 8 Hz, 1H), 7.05–7.25 (m,
2H), 7.46 (d, J = 8 Hz, 1H), 7.69 (d, J = 8 Hz, 1H), 7.78 (d, J = 2 Hz, 1H), 7.97 (s, 1H), 11.77 (br s,
1
3
1
1
6
H), 12.16 (br s, 1H); C NMR (DMSO-d , 50 MHz) δ 17.6, 25.6, 28.3, 44.0, 51.5, 109.8, 112.1,
18.0, 120.3, 122.2, 122.4, 124.9, 126.7, 127.5, 131.9, 132.4, 135.8, 167.3, 174.0; ESIMS (m/z) 350
+
[M+Na] ; HRMS (ESI) calcd for C19
H
21
O
4
NNa 350.1363, found 350.1357; IR (nujol) νmax 3372,
1
−
1
704, 1613 cm .
Methyl 1-Hydroxy-2-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carboxylate (4). To a solution of
compound 3 (4.00 g, 12.23 mmol) in DCM (25 mL) at ‒10 °C was added triethylamine (1.70 mL,
2.23 mmol) and triphosgene (5.43 g, 18.34 mmol) and the reaction mixture was stirred at ‒10 to 0 °C
1
for 2 h. Reaction mixture was concentrated in vacuo and the obtained residue was dissolved in ethyl
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2 4
acetate (150 mL). The organic layer was washed with water, brine and dried over Na SO .
Concentration of organic layer in vacuo followed by silica gel (60‒120 mesh) column
chromatographic purification of the obtained residue using ethyl acetate‒petroleum ether (3:7) as an
10
11
12
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60
1
eluent provided product 4 as gummy solid (2.42 g, 64%). H NMR (CDCl
3
, 400 MHz) δ 1.80 (s, 3H),
1.91 (s, 3H), 4.00 (br s, 5H), 5.40 (t, J = 8 Hz, 1H), 5.98 (s, 1H), 7.22–7.30 (m, 1H), 7.40–7.48 (m,
1
3
2
2
3
H), 8.07 (d, J = 8 Hz, 1H), 8.34 (br s, 1H), 8.56 (br s, 1H); C NMR (CDCl , 100 MHz) δ 17.9, 25.7,
6.5, 52.0, 111.1, 116.7, 120.0, 120.5, 121.7, 122.2, 122.4, 123.65, 123.74, 126.1, 132.1, 134.8, 139.8,
+
140.5, 169.3; ESIMS (m/z) 332 [M+Na] ; HRMS (ESI) calcd for C19
H
19
O
3
NNa 332.1257, found
1
−
3
32.1270; IR (CHCl
3
) νmax 3362, 1701, 1646 cm .
Methyl 1-Methoxy-2-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carboxylate (5). To a stirred
solution of compound 4 (2.00 g, 6.47 mmol) in dry acetone (20 mL) was added K CO (893 mg, 6.47
2
3
mmol) and dimethyl sulphate (494 µl, 5.17 mmol) at 25 °C and the reaction mixture was refluxed for 8
h. The reaction mixture was allowed to reach room temperature and concentrated in vacuo. The
obtained residue was dissolved in ethyl acetate (100 mL) and the organic layer was washed with water,
2
brine and dried over Na SO4. The organic layer was concentrated in vacuo and silica gel (60‒120
mesh) column chromatographic purification of the obtained residue using ethyl acetate‒petroleum
1
ether (2:8) as eluent yielded pure product 5 as a white solid (1.91 g, 91%). Mp 130‒132 °C; H NMR
(CDCl
3
, 400 MHz) δ 1.71 (s, 3H), 1.84 (s, 3H), 3.94 (s, 2H), 3.96 (s, 6H), 5.27 (t, J = 8 Hz, 1H), 7.28
13
(
t, J = 8 Hz, 1H), 7.40–7.50 (m, 2H), 8.07 (d, J = 8 Hz, 1H), 8.38 (br s, 1H), 8.49 (s, 1H); C NMR
(CDCl
3
, 100 MHz) δ 18.1, 25.7, 25.9, 51.9, 61.1, 111.0, 120.1, 120.3, 120.5, 122.5, 122.6, 123.9,
+
124.1, 126.3, 131.3, 133.3, 135.5, 139.8, 143.2, 168.7; ESIMS (m/z) 346 [M+Na] ; HRMS (ESI) calcd
‒1
21 3 3
for C20H O NNa 346.1414, found 346.1409; IR (CHCl )νmax 3468, 1706, 1608 cm .
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6
(
1-Methoxy-2-(3-methylbut-2-en-1-yl)-9H-carbazol-3-yl)methanol (6). To a stirred solution of
compound 5 (120 mg, 0.37 mmol) in THF (5 mL) was added solution of DIBAL-H in toluene (1 M,
.11 mL, 1.11 mmol) at ‒78 °C under argon atmosphere. The reaction mixture was stirred at ‒78 to 25
C for 3 h. The reaction was quenched by saturated sodium‒potassium tartarate solution and stirred for
h. The reaction mixture was concentrated in vacuo and obtained residue was dissolved in diethyl
ether (30 mL). The organic layer was washed with water, brine and dried over Na SO . The organic
1
0
1
2
3
4
5
6
7
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9
0
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2
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9
0
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
°
1
2
4
layer was concentrated in vacuo and silica gel (60‒120 mesh) column chromatographic purification of
the resulting residue using ethyl acetate‒petroleum ether (3:7) as an eluent furnished pure product 6 as
1
a white solid (96 mg, 88%). Mp 142‒144 °C; H NMR (CDCl
3
, 200 MHz) δ 1.73 (s, 3H), 1.87 (s, 3H),
3
.67 (d, J = 6 Hz, 2H), 3.97 (s, 3H), 4.83 (s, 2H), 5.15–5.27 (m, 1H), 7.24 (t, J = 8 Hz, 1H), 7.35–7.50
13
(
3
m, 2H), 7.87 (s, 1H), 8.03 (d, J = 6 Hz, 1H), 8.20 (br s, 1H); C NMR (CDCl , 100 MHz) δ 18.0,
25.1, 25.7, 61.1, 64.2, 110.9, 116.8, 119.7, 120.3, 123.3, 123.9, 124.0, 125.7, 130.0, 131.9, 132.1,
+
1
32.8, 139.6, 143.2; ESIMS (m/z) 318 [M+Na] ; HRMS (ESI) calcd for C19
H
21
O
2
NNa 318.1465,
1
−
found 318.1477; IR (CHCl
3
)νmax 3451 cm .
7
1-Methoxy-2-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde (Indizoline, 7). To a
mixture of compound 6 (70 mg, 0.237 mmol) and celite (100 mg) in DCM (10 mL) was added PCC
(102 mg, 0.47 mmol) at 25 °C under argon atmosphere and the reaction mixture was stirred for 30 min
at same temperature. The reaction mixture was filtered and the filtrate was concentrated in vacuo.
Direct silica gel (60‒120 mesh) column chromatographic purification of the resulting residue using
ethyl acetate‒petroleum ether (2:8) as an eluent furnished aldehyde 7 as gummy solid (66 mg, 95%).
1
H NMR (CDCl
3
, 400 MHz) δ 1.70 (s, 3H), 1.85 (s, 3H), 3.95 (s, 2H), 3.97 (s, 3H), 5.24 (t, J = 8 Hz,
1
1
H), 7.30 (t, J = 8 Hz, 1H), 7.40–7.52 (m, 2H), 8.08 (d, J = 8 Hz, 1H), 8.44 (s, 1H), 8.52 (br s, 1H),
1
3
0.29 (s, 1H); C NMR (CDCl
3
, 100 MHz) δ 18.1, 24.1, 25.7, 61.4, 111.2, 120.7, 120.8, 121.1, 123.3,
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23.8, 124.0, 126.7, 127.8, 132.0, 134.0, 136.9, 139.8, 142.8, 191.9; ESIMS (m/z) 294 [M+H] ;
19 2 3
HRMS (ESI) calcd for C19H O NNa 316.1308, found 316.1304; IR (CHCl )νmax 3302, 1725, 1659
1
−
cm .
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(
2-((3, 3-Dimethyloxiran-2-yl) methyl)-1-methoxy-9H-carbazol-3-yl)methanol (9). To a
solution of compound 6 (60 mg, 0.203 mmol) in DCM (5 mL) was added m-CPBA (34.98 mg, 0.203
mmol) at ‒10 °C under argon atmosphere and the reaction mixture was stirred for 15 min. The reaction
was quenched with saturated solution of NaHCO
3
at 0 °C. The reaction mixture extracted with DCM
(
15 mL) and organic layer was immediately concentrated in vacuo to obtain epoxide 9 as a white solid
1
(43 mg, 72%). It was immediately characterized without any purification for stability issues. H NMR
acetone-d , 400 MHz) δ 1.29 (s, 3H), 1.47 (s, 3H), 2.99 (dd, J = 20 and 4 Hz, 2H), 3.34 (dd, J = 12
and 4 Hz, 1H), 3.95−4.10 (br s, 1H), 4.01 (s, 3H), 4.80 (d, J = 4 Hz, 2H), 7.17 (t, J = 8 Hz, 1H), 7.37
(
6
1
3
(t, J = 8 Hz, 1H), 7.52 (d, J = 8 Hz, 1H), 7.91 (s, 1H), 8.07 (d, J = 8 Hz, 1H), 10.41 (br s, 1H); C
NMR (acetone-d
6
, 100 MHz) δ 19.4, 25.0, 26.5, 59.9, 61.1, 64.1, 65.4, 112.1, 117.2, 119.9, 120.9,
1
24.55, 124.57, 126.4, 127.5, 133.4, 133.9, 141.4, 144.9; ESIMS (m/z); HRMS (ESI) calcd for
1
−
C
19
H
21
O
3
3
NNa 334.1414, found 334.1410; IR (CHCl ) νmax 3453 cm .
2
-(5-Methoxy-1,3,4,6-tetrahydropyrano[4,3-b]carbazol-3-yl)propan-2-ol
(Proposed
1
1
Claulamine E, 10).
Method A: To a solution of compound 6 (60 mg, 0.203 mmol) in DCM (5 mL) was added m-CPBA
34.98 mg, 0.203 mmol) at ‒10 °C under argon atmosphere and the reaction mixture was stirred for 4
h at 25 °C. The reaction was quenched with saturated solution of NaHCO at 25 °C. The reaction
mixture was extracted with DCM (10 mL x 2) and combined organic layer was washed with water,
(
3
brine and dried over Na
2
SO4. Concentration of organic layer in vacuo followed by silica gel (60‒120
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5
6
mesh) column chromatographic purification of the resulting residue using ethyl acetate‒petroleum
ether (2:8) as an eluent furnished product 10 as a white solid (53 mg, 83%).
Method B: The solution of compound 9 (20 mg, 0.064 mmol) in acetone (1 mL) was stirred at 25 °C
for 10 h. The reaction mixture was concentrated in vacuo and silica gel (60‒120 mesh) column
chromatographic purification of the resulting residue using ethyl acetate‒petroleum ether (2:8) as an
eluent furnished product 10 as a white solid (19 mg, 96%).
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
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7
8
9
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0
Method C: Mixture of compound 13 (50 mg, 0.15 mmol) and p-TSA (52 mg, 0.30 mmol) in THF (5
mL) was stirred at 25 °C for 2 h. The reaction mixture was concentrated in vacuo and obtained residue
was dissolved in ethyl acetate (20 mL). The organic layer was washed with water, brine and dried over
2
Na SO4. Concentration of organic layer in vacuo followed by silica gel (60‒120 mesh) column
chromatographic purification of the resulting residue using ethyl acetate‒petroleum ether (2:8) as an
1
eluent furnished product 10 as a white solid (38 mg, 81%). Mp 160‒162 °C; H NMR (acetone-d
6
, 500
MHz) δ 1.28 (s, 3H), 1.29 (s, 3H), 2.80−2.90 (m, 1H), 3.10 (dd, J = 15 and 5 Hz, 1H), 3.44 (br s, 1H),
.49 (dd, J = 10 and 5 Hz, 1H), 3.96 (s, 3H), 4.92 (d, J = 15 Hz, 1H), 5.05 (d, J = 15 Hz, 1H), 7.14 (t, J
= 10 Hz, 1H), 7.36 (t, J = 10 Hz, 1H), 7.50 (d, J = 10 Hz, 1H), 7.55 (s, 1H), 8.02 (d, J = 10 Hz, 1H),
3
1
3
1
1
6
0.31 (br s, 1H); C NMR (acetone-d , 125 MHz) δ 24.2, 25.7, 26.4, 60.4, 70.0, 72.0, 82.7, 111.7,
12.0, 119.7, 120.9, 124.35, 124.43, 124.7, 126.5, 127.8, 132.8, 141.5, 143.9; ESIMS (m/z) 334
+
[M+Na] ; HRMS (ESI) calcd for C19
H
21
O
3
NNa 334.1414, found 334.1409; IR (CHCl
3
) νmax 3685,
1
−
3
468 cm .
3-(2-Hydroxypropan-2-yl)-5-methoxy-4,6-dihydropyrano[4,3-b]carbazol-1(3H)-one
8
(
Mafaicheenamine A, 11). To a stirred solution of compound 5 (500 mg, 1.54 mmol) in t-BuOH (15
mL) was added OsO
4
in t-BuOH (1 M, 308 µL, 0.308 mmol) and 50% aqueous NMO solution (540
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µL) at 25 °C and the reaction mixture was stirred for 15 h. The reaction was quenched with saturated
solution of NaHSO
3
and stirred at 25 °C for next 1 h. The reaction mixture was extracted with ethyl
acetate (3 × 10 mL) and combined organic layer washed with water, brine and dried over Na
2
SO4. The
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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29
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60
organic layer was concentrated in vacuo and silica gel (60‒120 mesh) column chromatographic
purification of the obtained residue using ethyl acetate‒petroleum ether (8:2) as eluent yielded pure
1
product 11 as a colorless solid (435 mg, 86%). Mp 236‒238 °C; H NMR (acetone-d
6
, 500 MHz) δ
1
3
.38 (s, 6H), 3.04 (dd, J = 15 and 15 Hz, 1H), 3.46 (dd, J = 15 and 5 Hz, 1H), 3.92 (br s, 1H), 4.00 (s,
H), 4.30 (dd, J = 10 and 5 Hz, 1H), 7.27 (t, J = 10 Hz, 1H), 7.46 (t, J = 10 Hz, 1H), 7.59 (d, J = 10
1
3
Hz, 1H), 8.23 (d, J = 10 Hz, 1H), 8.60 (s, 1H), 10.86 (br s, 1H); C NMR (acetone-d
6
, 125 MHz) δ
2
1
3.3, 25.5, 26.9, 61.4, 71.3, 85.2, 112.5, 118.1, 119.9, 121.0, 121.5, 124.5, 124.9, 127.5, 129.6, 137.5,
+
41.7, 142.1, 166.3; ESIMS (m/z) 326 [M+H] ; HRMS (ESI) calcd for C19
H
20
O
4
N 326.1387, found
1
−
326.1383; IR (CHCl
3
) νmax 3687, 3462, 1707, 1614 cm .
5
-Methoxy-3-(prop-1-en-2-yl)-4,6-dihydropyrano[4,3-b]carbazol-1(3H)-one (Claulamine A,
9
1
2). To a stirred solution of compound 11 (50 mg, 0.153 mmol) in dry DCM (5 mL) was added
Burgess reagent (72.82 mg, 0.306 mmol) at 25 °C under argon atmosphere and the reaction mixture
was stirred for 48 h. The reaction mixture was diluted with EtOAc (20 mL) and organic layer was
2 4
washed with water, brine and dried over Na SO . Concentration of organic layer in vacuo followed by
silica gel (60‒120 mesh) column chromatographic purification of the obtained residue using ethyl
acetate‒petroleum ether (3:7) as an eluent yielded pure 12 as a white solid (35 mg, 74%). Mp 170‒174
1
°C; H NMR (CDCl
3
, 200 MHz) δ 1.95 (s, 3H), 3.14 (dd, J = 18 and 6 Hz, 1H), 3.38 (dd, J = 16 and 4
Hz, 1H), 3.99 (s, 3H), 4.96 (dd, J = 12 and 4 Hz, 1H), 5.07 (s, 1H), 5.21 (s, 1H), 7.27−7.35 (m, 1H),
1
3
7
3
.43−7.55 (m, 2H), 8.08 (d, J = 8 Hz, 1H), 8.56 (br s, 1H), 8.71 (s, 1H); C NMR (CDCl , 125 MHz)
δ 18.4, 26.9, 61.2, 81.0, 111.2, 113.9, 117.2, 120.0, 120.8, 120.9, 123.7, 124.4, 126.9, 127.7, 136.2,
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+
1
39.8, 140.6, 142.1, 166.5; ESIMS (m/z) 308 [M+H] ; HRMS (ESI) calcd for C19
H
18
O
3
N 308.1281,
1
−
found 308.1275; IR (CHCl
3
) νmax 3460, 1709, 1615 cm .
1
-(3-(Hydroxymethyl)-1-methoxy-9H-carbazol-2-yl)-3-methylbutane-2,3-diol (13). To a stirred
0
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2
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4
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solution of compound 11 (80 mg, 0.246 mmol) in THF (8 mL) was added solution of DIBAL-H in
toluene (1 M, 984 µL, 0.984 mmol) at ‒78 °C under argon atmosphere. The reaction mixture was
stirred at ‒78 to 25 °C for 4 h. The reaction was quenched by saturated sodium‒potassium tartarate
solution and stirred for 1 h. The reaction mixture was concentrated in vacuo and obtained residue was
stirred with diethyl ether (25 mL). The organic layer was washed with water, brine and dried over
2 4
Na SO . The organic layer was concentrated in vacuo and silica gel (60‒120 mesh) column
chromatographic purification of the resulting residue using ethyl acetate‒petroleum ether (7:3) as an
1
eluent furnished pure product 13 as gummy solid (64 mg, 79%). H NMR (CD
3
OD, 500 MHz) δ 1.32
(
s, 3H), 1.33 (s, 3H), 2.84 (dd, J = 15 and 10 Hz, 1H), 3.30 (dd, J = 10 and 5 Hz, 1H), 3.71 (dd, J = 10
and 5 Hz, 1H), 4.00 (s, 3H), 4.67 (d, J = 15 Hz, 1H), 4.90 (d, J = 15 Hz, 1H), 7.13 (t, J = 10 Hz, 1H),
.34 (t, J = 10 Hz, 1H), 7.47 (d, J = 10 Hz, 1H), 7.78 (s, 1H), 7.99 (d, J = 10 Hz, 1H), 10.68 (br s, 1H);
7
1
3
C NMR (CD
3
OD, 125 MHz) δ 25.5, 25.6, 29.8, 60.8, 64.8, 74.3, 79.8, 112.2, 118.2, 120.1, 121.0,
+
1
24.9, 125.0, 126.7, 129.5, 132.9, 134.4, 142.0, 145.4; ESIMS (m/z) 352 [M+Na] ; HRMS (ESI) calcd
1
−
for C19
H
23
O
4
NNa 352.1519, found 352.1513; IR (CHCl
3
) νmax 3438, 1660 cm .
6-Methoxy-3,3-dimethyl-3,4,5,7-tetrahydro-1H-1,4-epoxyoxepino[4,3-b]carbazole
10
(Claulansine A, 14).
Method A: To a stirred solution of compound 11 (60 mg, 0.184 mmol) in THF (6 mL) was added
solution of DIBAL-H in toluene (1 M, 553 µL, 0.553 mmol) at ‒78 °C under argon atmosphere. The
reaction mixture was stirred at ‒78 °C for 3 h. The reaction was quenched by saturated sodium‒
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potassium tartarate solution and stirred for 1 h. The reaction mixture was concentrated in vacuo and
obtained residue was dissolved in diethyl ether (25 mL). The organic layer was washed with water,
2 4
brine and dried over Na SO . Concentration of organic layer in vacuo followed silica gel (60‒120
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11
12
13
14
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16
17
18
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43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
mesh) column chromatographic purification of the resulting residue using ethyl acetate‒petroleum
ether (3:7) as an eluent provided product 14 as a white solid (44 mg, 77%).
Method B: To a solution of compound 13 (30 mg, 0.091 mmol) in DCM (5 mL) was added PCC
(39.13 mg, 0.182 mmol) at 25 °C and the reaction mixture was stirred for 15 h. The reaction mixture
was filtered and concentrated in vacuo. Silica gel (60‒120 mesh) column chromatographic purification
of the obtained residue using ethyl acetate‒petroleum ether (3:7) as an eluent provided product 14 as a
1
white solid (20 mg, 70%). Mp 180‒182 °C; H NMR (DMSO-d
6
, 400 MHz) δ 1.15 (s, 3H), 1.27 (s,
3
7
H), 3.01 (d, J = 16 Hz, 1H), 3.22 (dd, J = 16 and 4 Hz, 1H), 3.91 (s, 3H), 4.49 (s, 1H), 6.10 (s, 1H),
.14 (t, J = 8 Hz, 1H), 7.36 (t, J = 8 Hz, 1H), 7.49 (d, J = 8 Hz, 1H), 7.61(s, 1H), 8.02 (d, J = 8 Hz,
1
3
1H), 11.33 (s, 1H); C NMR (DMSO-d
6
, 100 MHz) δ 23.7, 25.6, 29.4, 59.8, 79.2, 79.9, 100.4, 111.3,
+
1
11.8, 118.8, 119.9, 120.2, 122.2, 122.9, 125.4, 130.1, 132.4, 139.9, 142.5; ESIMS (m/z) 310 [M+H] ;
1
−
HRMS (ESI) calcd for C19
H
20
O
3
3
N 310.1438, found 310.1433; IR (CHCl ) νmax 3417, 1603 cm .
(1-Methoxy-4-(3-methylbut-2-en-1-yl)-9H-carbazol-3-yl)methanol (16). To a stirred solution of
compound 15 (100 mg, 0.30 mmol) in THF (5 mL) was added solution of DIBAL-H in toluene (1 M,
900 µL, 0.90 mmol) at ‒78 °C under argon atmosphere and the reaction mixture was stirred at ‒78 to
2
5 °C for 3 h. The reaction was quenched by saturated sodium‒potassium tartarate solution and stirred
for 1 h. The reaction mixture was concentrated in vacuo and obtained residue was dissolved in diethyl
ether (30 mL). The organic layer was washed with water, brine and dried over Na SO . The organic
2
4
layer was concentrated in vacuo and silica gel (60‒120 mesh) column chromatographic purification of
the resulting residue using ethyl acetate‒petroleum ether (3:7) as an eluent furnished pure product 16
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as gummy solid (80 mg, 87%). H NMR (CDCl
3
, 400 MHz) δ 1.71 (s, 3H), 1.94 (s, 3H), 4.00 (s, 2H),
4
1
1
.01 (s, 3H), 4.85 (s, 2H), 5.33 (t, J = 8 Hz, 1H), 6.96 (s, 1H), 7.25 (t, J = 8 Hz, 1H), 7.43 (t, J = 8 Hz,
1
3
3
H), 7.49 (d, J = 8 Hz, 1H), 8.13 (d, J = 8 Hz, 1H), 8.38 (br s, 1H); C NMR (CDCl , 100 MHz) δ
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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2
3
4
5
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7
8
9
0
8.3, 25.7, 28.1, 55.6, 64.0, 107.7, 110.9, 119.5, 122.8, 123.0, 123.2, 123.7, 125.3, 127.8, 129.7,
+
129.9, 132.5, 139.6, 143.6; ESIMS (m/z) 318 [M+Na] ; HRMS (ESI) calcd for C19
H
21
O
2
NNa
1
−
3
18.1465, found 318.1466; IR (CHCl
3
) νmax 3595, 3468 cm .
(
4-((3,3-Dimethyloxiran-2-yl)methyl)-1-methoxy-9H-carbazol-3-yl)methanol (17). To a
solution of compound 16 (70 mg, 0.237 mmol) in DCM (5 mL) was added m-CPBA (40 mg, 0.237
mmol) at ‒30 °C under argon atmosphere and the reaction mixture was stirred for 2.5 h below –10 °C.
The reaction was quenched with saturated solution of NaHCO
extracted with DCM (10 mL × 2) and combined organic layer was washed with water, brine and dried
over Na SO4. The concentration of organic layer in vacuo followed by silica gel (60‒120 mesh)
3
at 25 °C. The reaction mixture was
2
column chromatographic purification of resulting residue using ethyl acetate‒petroleum ether (3:7) as
1
an eluent furnished product 17 as a white solid (60 mg, 81%). Mp 166‒168 °C; H NMR (acetone-d
6
,
500 MHz) δ 1.29 (s, 3H), 1.56 (s, 3H), 3.11 (dd, J = 5 and 5 Hz, 1H), 3.27 (dd, J = 15 and 10 Hz, 1H),
.84 (dd, J = 15 and 5 Hz, 1H), 3.86 (br s, 1H), 4.00 (s, 3H), 4.68 (d, J = 10 Hz, 1H), 4.82 (d, J = 10
Hz, 1H), 7.06 (s, 1H), 7.20 (t, J = 10 Hz, 1H), 7.40 (t, J = 10 Hz, 1H), 7.62 (d, J = 10 Hz, 1H), 8.27 (d,
3
1
3
J = 10 Hz, 1H), 10.45 (br s, 1H); C NMR (acetone-d
6
, 125 MHz) δ 19.5, 25.1, 29.1, 56.0, 60.6, 63.5,
6
3
1
4.8, 109.0, 112.4, 119.9, 123.1, 123.6, 124.3, 124.8, 125.9, 131.0, 132.9, 141.4, 145.1; ESIMS (m/z)
+
34 [M+Na] ; HRMS (ESI) calcd for C19
H
21
O
3
NNa 334.1414, found 334.1412; IR (CHCl
3
) νmax 3424,
1
−
640 cm .
ASSOCIATED CONTENT
Supporting Information
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H NMR, C NMR and DEPT spectra of all compounds, 2D NMR spectra of compounds 10 and 17,
and the X-ray crystallographic data for compound 10. This material is available free of charge via the
Internet at http://pubs.acs.org
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11
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AUTHOR INFORMATION
Corresponding Author
*
np.argade@ncl.res.in
ACKNOWLEDGMENT
S. B. M. thanks CSIR, New Delhi, for the award of research fellowship. N. P. A. thanks Department of
Science and Technology, New Delhi for financial support.ꢀWe gratefully acknowledge the financial
support from CSIR-Network Project. We thank Dr. P. R. Rajamohanan, Head Central NMR Facility,
NCL, Pune for important discussion on 2D NMR data. We are thankful to Mr. Shridhar H. Thorat and
Dr. Rajesh G. Gonnade from NCL, Pune for the X-ray crystallographic data.
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(
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(
27) Kamat, D. P.; Parsekar, S. B.; Kamat, V. P.; Tilve, S. G. Synthesis 2014, 46, 2789.
1
3
(
28) Inadvertent typographical errors were noticed in the tabulated C NMR data for natural product
1
3
claulamine A (12); please see the actual C NMR spectrum provided in the supporting information
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part of ref. 9.
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