Unexpected reaction of melatonin derivatives with performic acid

Article abstract of DOI:10.1016/j.crci.2013.03.005

A series of carbamate melatonin derivatives was treated with performic acid, providing tricyclic products with a 3-hydroxytetrahydropyrrolo[2,3-b] indole skeleton. An unusual migration of carbamate groups was observed in some cases, and the reaction appea

Full text of DOI:10.1016/j.crci.2013.03.005

C. R. Chimie 16 (2013) 807–813
Contents lists available at SciVerse ScienceDirect
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Full paper/M e´ moire
Unexpected reaction of melatonin derivatives with performic acid
a
a
a
a
b
˙
Zuzanna Mol e˛ da , Anna Zawadzka , Małgorzata Zytek , Daria Madej , Franciszek Pluci n´ ski ,
b,c
a,
Jan K. Maurin , Zbigniew Czarnocki *
a
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warszawa, Poland
b
National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland
c
´
National Centre for Nuclear Research, Sołtana 7, 05-400 Otwock-Swierk, Poland
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of carbamate melatonin derivatives was treated with performic acid, providing
tricyclic products with a 3-hydroxytetrahydropyrrolo[2,3-b]indole skeleton. An unusual
migration of carbamate groups was observed in some cases, and the reaction appeared to
be strongly dependent on the type of substituent in the phenyl ring of the
phenylcarbamate group. Theoretical calculations suggest that the reaction is kinetically
controlled.
Received 11 January 2013
Accepted after revision 18 March 2013
Available online 24 April 2013
Keywords:
Cyclization
Indoles
ß 2013 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Oxygenations
Rearrangement
Ring closure
R E´ S U M E´
Une s e´ rie de d e´ riv e´ es de la m e´ latonine carbamate a e´ t e´ trait e´ e avec de l’acide performique,
fournissant des produits tricycliques avec un squelette 3-hydroxyt e´ trahydropyrrolo [2,3-
b] indole. Une migration inhabituelle des groupes carbamate a e´ t e´ observ e´ e dans certains
cas, et la r e´ action a sembl e´ eˆ tre fortement d e´ pendante du type de substituant sur le noyau
ph e´ nyle du groupe ph e´ nylcarbamate.
ß 2013 Acad e´ mie des sciences. Publi e´ par Elsevier Masson SAS. Tous droits r e´ serv e´ s.
1
. Introduction
a-Hydroxytetrahydropyrrolo[2,3-b]indole is the
cyclization of indole derivatives seems to be the simplest
one [5]. An example of such reaction is the oxidation of
melatonin 1 with singlet oxygen, in the presence of
photosensitizers, such as Bengal rose at ꢀ78 8C, to produce
cyclic 3-hydroxymelatonin 2 [6] (Scheme 1).
3
structural motif characteristic of many compounds of
high biological importance, such as notoamide D –
obtained from
a
culture of marine-derived fungus
We have recently demonstrated that compounds
possessing a carbamate substituent at position 5 of the
3a-hydroxytetrahydropyrrolo[2,3-b]indole skeleton exhi-
bit a high inhibitory activity against human cholines-
terases [7]. This type of compounds represents an
interesting synthetic target, poorly explored so far.
It was reported that the oxidation of carbamate
melatonin derivatives with singlet oxygen results in the
cyclization to 3a-hydroxytetrahydropyrrolo[2,3-b]indole
system [7]. Unfortunately, this method turns out to be
time-consuming and merely effective due to a low degree
of conversion.
Aspergillus sp. and which demonstrated noticeable cyto-
toxity on HeLa and L-1210 tumor cells [1] –, gypsetin –
derived from dermatophyte Nannizzia gypsea and which
confirmed acyl-CoA acyltransferase inhibitory activity
[
2] – or himastatin – a new anti-tumor antibiotic from
Streptomyces hygroscopicus [3]. Among the several possi-
ble methods for the synthesis of this system [4], oxidative
*
Corresponding author.
E-mail address: czarnoz@chem.uw.edu.pl (Z. Czarnocki).
1
631-0748/$ – see front matter ß 2013 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.03.005

8
08
Z. Mol e˛ da et al. / C. R. Chimie 16 (2013) 807–813
O
HO
O , hv, Bengal rose
MeOH, PyH, -78 C
2
H CO
3
N
H
H CO
o
3
CH3
N
O
N
H
H
N
H
CH3
2
1
Scheme 1. Oxidation of melatonin 1 with singlet oxygen.
O
HO
HCOOH/H O
H
N
2
2
H
N
O
N
H
o
O
0 C, 2h
CH3
N
O
(a)
O
N
H
O
30%
N
H
CH3
O
4
3
O
HCOOH/H O
HO
H
N
2
2
H
N
H
O
o
N
O
CH3
0 C, 2h
(
b)
N
O
O
O
N
H
39%
N
H
Cl
Cl
CH3
O
5
6
O
NO2
HCOOH/H
2
O
2
NO
2
HO
H
o
H
N
N
0 C, 2h
N
O
O
H
CH3
N
O
(
c)
1
2%
O
O
N
N
H
H
CH
3
O
7
8
Scheme 2. Oxidation of 3-[2-(acetylamino)ethyl]-1H-indol-5-yl carbamates 3, 5 and 7 with performic acid.
2
. Results and discussion
We have, therefore, investigated a series of reactions of
can be explained by the already documented formulating
ability of performic acid [9]. Postulated structure of the
product was confirmed by X-ray analysis (Fig. 1).
melatonin 1 and its derivatives with different oxidative
reagents, in order to find an easy and more efficient
method for the synthesis of the desirable tricyclic system.
In the case of carbamates 5 and 7, we obtained similar
results. The reaction yields were not high but still
satisfying in comparison with the methods used so far.
This disadvantage was in addition compensated by the
2 2
Unfortunately, we found that the oxidation with H O ,
1
2 2 3
NaOCl, MnO , SeO , CrO , Oxone , or Sharpless epoxidat-
ing reagent was, depending on the conditions used, either
completely ineffective, or resulted in the decomposition of
the substrate to unidentifiable products. Attempts to
oxidize melatonin 1 with peracids seemed to be the most
promising.
In order to obtain the 3a-hydroxytetrahydropyrrolo-
[
2,3-b]indole skeleton substituted at position 5 with a
carbamate group, we subjected 3-[2-(acetylamino)ethyl]-
H-indol-5-yl carbamates to a reaction with performic
acid, freshly prepared by adding H to concentrated
formic acid according to the known procedure [8] (Scheme
).
1
2 2
O
2
We were pleased to observe the fast consumption of the
substrate as well as the formation of a single product, easy
to isolate. The oxidation of 3-[2-(acetylamino)ethyl]-1H-
indol-5-yl phenylcarbamate 3 resulted in the desired
tricyclic product 4, with undisturbed carbamate moiety.
An additional formulation of the N8 atom occurred, which
1
Fig. 1. ORTEP diagram from X-ray analysis of compound 4 .

Z. Mol e˛ da et al. / C. R. Chimie 16 (2013) 807–813
809
HO
HO
N
O
H C
CH3
O
3
HCOOH/H O
N
H
2
2
C
H
H
o
N
H
0 C, 2h
N
O
O
3
CH3
HN
H C
(a)
3
O
31%
N
H
H C
3
9
10
HO
HO
O
N
O
CH3
HCOOH/H O
H
2
2
N
H
N
H
N
O
o
CH3
0 C, 2h
O
(b)
H C
3
O
HN
N
H
24%
CH3
1
1
12
CH3
H C
3
HO
HO
O
HCOOH/H O
OCH3
2
2
N
O
CH3
H
o
N
H
0 C, 2h
N
O
CH3
N
H
O
(
c)
2
6%
O
N
H
HN
H CO
3
13
1
4
Scheme 3. Oxidation of 3-[2-(acetylamino)ethyl]-1H-indol-5-yl carbamates 9, 11 and 13 with performic acid.
simplicity of the reaction and purification procedure and
the low cost of the reagents used. The substrates may be
easily recovered and recycled. The yields calculated on a
basis of the consumed substrates were almost quanti-
tative.
Hoping to have in hand a general method for the
synthesis of tricyclic carbamates, we decided to broaden
the spectrum of the investigated substituents at the
aromatic ring of the phenylcarbamate moiety. Therefore,
we used the previously optimized methodology to oxidize
o-isopropylphenyl-, p-isopropylphenyl- and o-methoxy-
phenyl-carbamates (Scheme 3).
succeeded to obtain a monocrystal suitable for X-ray
analysis and we were surprised to find out that the
carbamate bond hydrolyzed and the released group
formed a urea bond with the N8 atom of the tricyclic
system (Figs. 2 and 3). Detailed spectral analysis further
confirmed the proposed structure of the products 10, 12
and 14.
Surprised by the difference in the results obtained for
carbamates 3, 5, 7 and 9, 11, 13, we repeated all the
reactions several times, changing the concentration of the
oxidizing agent and we gained a conviction that it does not
affect the type of product. We can then assume that the
structure of the product depends only on the substrate
used. Unexpected influence of the substituent at the
phenyl ring on the reaction course can be attributed to the
presence of a conjugated bonds system, which covers a
considerable part of the molecule of the substrate and can
generate unexpectedly strong long-distance electronic
effects. In order to rationalize the differences in the
reactivity of various carbamates with performic acid, we
Similarly to our previous results, we observed the
formation of a single product with the yield of around
3
0%. In the NMR spectra, we identified signals char-
acteristic of the tricyclic system but, surprisingly, no
signal from the expected formyl group was present. The
mass spectrometry analysis confirmed the absence of
the formyl substituent in all the three cases mentioned.
For the products possessing p-isopropyl substituents, we

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Z. Mol e˛ da et al. / C. R. Chimie 16 (2013) 807–813
HO
HO
HO
HO
N
N
O
O
N
H
N
H
CH3
CH3
O
O
HN
HN
O N
2
15
Cl
16
OCH3
HO
H
N
O
N
O
O
N
H
CH3
O
17
2
Fig. 2. ORTEP diagram from X-ray analysis of compound 10 . For
interpretation of colors, see the web version of this article.
Fig. 4. The structures of the alternative products 15, 16, 17 used for
calculations.
function basis were performed. The structure of the
molecules of the products and substrates were optimized
and their free enthalpies were calculated. The results are
summarized in Table 1.
These results of calculations indicate that due to rather
0
minute differences in
D
G
values, the thermodynamic
influence is not significant and apparently the reaction is
governed by kinetic factors.
The course of the reaction, leading to unexpected
products listed in Scheme 3, might be explained by a
process starting with the protonation of the carbamate
oxygen atom followed by the formation of the reaction
intermediate whose sandwich-like dimeric structure
allows the simultaneous transfer of both carbamate units
between the molecules and the subsequent formation of
the observed product. The example of such reaction
sequence for compound 13 is shown in Scheme 4. We
are aware that such a process might be highly unfavour-
able, leading to a dimeric structure of an extremely high
energy and the real reaction course is probably a multi-
step process but we hoped that our model would at least
illustrate the tendency to the appropriate bonds forming/
breaking sequence.
3
Fig. 3. ORTEP diagram from X-ray analysis of compound 12 . For
interpretation of colors, see the web version of this article.
initially concentrated on the thermodynamic aspects of
0
this reaction. The complete set of free enthalpy (
D
G )
We, therefore, compared two alternative processes of
the dissociation of the hypothetical dimeric structures: the
values for all the reactions leading to the products, both
observed and hypothetical (Fig. 4) were calculated using
the Spartan 08 software [10]. Ab initio calculations using
density functional method at B3LYP level with 6–31 + G*
CH3
CH3
O
H
N
O
Table 1
Comparison of free energy values for reactions leading to formed and
hypothetical products.
O
N
O
N
H
13
H
14
N
O
0
O
O
Entry
Substituent
Reaction
DG
[kJ/mol]
N
H
0
0
O
1
2
3
4
5
6
p-Cl
p-Cl
G (6)–G (5)
–66.8
–76.0
–75.3
–57.0
–67.1
–75.2
0
0
G (15)–G (5)
N
CH3
0
0
o-NO
o-NO
2
2
G (8)–G (7)
3
H C
0
0
G (16)–G (7)
13a
0
0
o-OCH
o-OCH
3
3
G (14)–G (13)
0
0
G (17)–G (13)
Scheme 4. The postulated mechanism for the formation of product 14.

Z. Mol e˛ da et al. / C. R. Chimie 16 (2013) 807–813
811
performic acid form the corresponding 3-hydroxytetrahy-
dropyrrolo[2,3-b]indoles. An unusual migration of carba-
mate groups was observed in some cases, and the reaction
appeared to be strongly dependent on the type of
substituent in the phenyl ring of the phenylcarbamate
group. Theoretical calculations suggest that the reaction is
kinetically controlled.
4. Experimental
Anhydrous solvents were used for all the reactions. TLC
Fig. 5. The optimized structure of postulated intermediate 13a. For
analyses were performed on silica gel plates (Merck Silica
Gel 60 F254) and made visual using a UV lamp and I vapor.
interpretation of colors, see the web version of this article.
2
The melting points were determined on a Boetius hot-plate
microscope and are uncorrected. Column chromatography
was carried out at atmospheric pressure using Merck Silica
Table 2
2 3
Gel 60 (100–200 mesh) or Al O using mixtures of
The comparison of energies (in kJ/mol) of alternative dissociation
processes.
cyclohexane–ethyl acetate or diethyl ether–methanol as
eluents. The NMR spectra were recorded on a Varian Unity
1
Intermediate
D
E
DDE
Plus spectrometer operating at 200 MHz or 500 MHz for H
1
3
C–N dissociation
C–O dissociation
NMR and at 50 MHz or 125 MHz for C NMR. The spectra
were measured in CDCl , CD OD and DMSO-d and
chemical shifts ( ) are reported in ppm relative to TMS.
3
3
6
5
7
1
a
–6199.0
–6202.2
–6358.6
–6252.4
–6223.2
–6041.8
53.4
21.0
d
a
3a
–316.8
Mass spectra were obtained using Quattro LC Micromass
and LCT Micromass TOF HiRes apparatus. 3-[2-(acetyla-
mino)ethyl]-1H-indol-5-yl carbamates 3, 5, 7, 9, 11 and 13
were prepared according to the known procedure [7]. The
X-ray data were collected using Oxford Diffraction
first one consisting in the dissociation of the C–N bonds
shown in red in Scheme 4) leading to a ‘‘normal’’ product
(
Xcalibur
collected at room temperature by the application of
Cu K monochromatic radiation. The structures were
R single crystal diffractometer. Data were
without rearrangement, and the second one consisting in
the dissociation of the phenolic C–O bond (marked in blue
in Scheme 4) leading to ‘‘rearranged’’ products.
To establish the energy of each process, we performed
an ab initio optimization of the structures of the respective
dimers (Fig. 5) and the corresponding monomers and then,
we compared the energy differences:
a
solved using SHELXS-93 program [10] and then refined by
the application of SHELXL-93 software [10]. Full structural
data have been deposited with the Cambridge Crystal-
lographic Data Centre under respective numbers CCDC
1
2
3
910337 , CCDC 910338 , and CCDC 910339 .
D
Eprocess ¼ 2Emonomer ꢀ Edimer
4.1. Oxidation of N-acetylserotonin carbamates with
Indeed, very high
not only bond energies but also repulsion and deformation
energies. The last column in Table 2 denoted as DD
D
E values of the processes encompass
performic acid. General procedure
E
Performic acid was freshly prepared by adding 30%
contains the differences between dissociation energies
listed in columns 2 and 3. These values show a possible
gain in energy when a new C–N bond is formed in a product
with a simultaneous dissociation of the existing C–O bond.
In all instances where such value is positive, the process is
unfavourable whereas negative value corresponds to a net
energy gain. The comparison of the energies listed in Table
2 2
H O (0.5 mL) to 98% formic acid (9.5 mL) and stirring at
room temperature for 2 h.
3-[2-(acetylamino)ethyl]-1H-indol-5-yl carbamate was
dissolved in 98% formic acid (2 mL). The mixture was
cooled to 0 8C and performic acid (1.1 equiv) was added.
The mixture was stirred at 0 8C for 2 h and washed with
2 3 2 3
10% aqueous Na SO solution (10 mL). Na CO (2 g) was
2
leads to the conclusion that the rearrangement process,
added successively. The mixture was extracted with CHCl
3
i.e. the breaking the C–O bond, is preferred for inter-
mediate 13a, whereas for the two others (5a and 7a), the
preferred one is the dissociation or more exactly the non-
formation of C–N bonds. These results are in agreement
with the experimental observations and seem to confirm a
plausible mechanism for the observed rearrangement.
(2 ꢁ 15 mL). The organic layer was dried over anhydrous
4
MgSO and concentrated.
1
The detailed structural parameters have been deposited with the
Cambridge Crystallographic Data Centre under the number CCDC 910337.
3
. Conclusion
2
The detailed structural parameters have been deposited with the
Cambridge Crystallographic Data Centre under the number CCDC 910338.
In summary, we found that certain melatonin deriva-
3
The detailed structural parameters have been deposited with the
tives possessing a carbamate moiety, when treated with
Cambridge Crystallographic Data Centre under the number CCDC 910339.

8
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Z. Mol e˛ da et al. / C. R. Chimie 16 (2013) 807–813
4
.1.1. 1-Acetyl-8-formyl-3a-hydroxy-1,2,3,3a,8,8a-
J = 2.5 Hz), 7.30 (dd, 1 H, J
1 H, J = 2.0 Hz, J = 7.5 Hz), 7.45 (d, 1 H, J = 9.0 Hz).
NMR (125 MHz, CD OD): = 22.08, 24.13, 30.74, 38.21,
1 2
= 2.0 Hz, J = 7.5 Hz), 7.34 (dd,
1
3
hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate 4
1
2
C
The residue was purified by column chromatography
3
d
(
1
CD
CH
silica gel, 0–5% MeOH–Et
2
O) to give a white solid; yield:
48.66, 84.14, 87.55, 110.84, 117.89, 120.36, 126.78,
126.99, 127.35, 128.20, 134.51, 136.29, 137.83, 145.40,
155.53, 157.75, 174.15. HRMS (ESI): m/z [M+Na]+ calcd for
1
68 mg (30%); mp 154–157 8C.
H
NMR (500 MHz,
), 2.46–2.57 (m, 2 H,
), 3,18 (m, 1 H, CHH), 3.87 (t, 1 H, J = 9.0 Hz, CHH), 5.87
3
OD):
d
= 2.09 (s, 3 H, COCH
3
2
22 25 3 4
C H N O Na: 418.1743, found: 418.1746. X-ray
2
(
s, 1 H, H-8a), 7.07 (t, 1 H, J = 7.0 Hz), 7.23 (dd, 1 H,
= 2.0 Hz, J = 9.0 Hz), 7.32 (t, 2 H, J = 8.0 Hz), 7.38 (d, 1 H,
J = 2.0 Hz), 7.51 (d, 2 H, J = 7.5 Hz), 8.02 (d, 1 H, J = 8.5 Hz),
analysis .
J
1
2
4.1.5. 1-Acetyl-3a,5-dihydroxy-N-(4-isopropylphenyl)-
2,3,3a,8a-tetrahydropyrrolo[2,3-b]indole-8(1H)-
carboxamide 12
13
8
3
1
1
C
3
.96 (s, 1 H, CHO). C NMR (125 MHz, CD OD): d = 21.01,
6.41, 46.84, 80.65, 85.18, 117.44, 117.98, 118.70, 123.37,
23.70, 128.81, 134.84, 138.57, 138.63, 148.48, 152.94,
63.31, 172.27. HRMS (ESI): m/z [M+Na]+ calcd for
The residue was purified by column chromatography
(silica gel, 0–5% MeOH–Et
2
O) to give a white solid; yield:
1
20
1
H
19
N
3
O
5
Na: 404.1223, found: 404.1226. X-ray analy-
65 mg (24%); mp 166–169 8C. H NMR (200 MHz, CD
3
OD):
CH), 2.17 (s, 3 H, COCH ),
), 2.85 (quin, 1 H, J = 6.4 Hz, (CH CH),
sis .
d
= 1.22 (d, 6 H, J = 7.8 Hz, (CH
3
)
2
3
2
.40 (m, 2 H, CH
2
3 2
)
4
.1.2. 1-Acetyl-8-formyl-3a-hydroxy-1,2,3,3a,8,8a-
3.08 (m, 1 H, CHH), 3.87 (m, 1 H, CHH), 5.81 (s, 1 H, H-8a),
6.78 (dd, 1 H, J = 2.4 Hz, J = 8.6 Hz), 6.86 (d, 1 H,
J = 2.6 Hz), 7.15 (d, H, J = 8.4 Hz), 7.40 (d, H,
J = 8.6 Hz), 7.47 (d, 1 H, J = 8.6 Hz). C NMR (50 MHz,
CD OD): = 22.30, 24.69, 34.96, 38.27, 48.72, 84.03, 87.63,
hexahydropyrrolo[2,3-b]indol-5-yl (4-
chlorophenyl)carbamate 6
1
2
2
2
1
3
The residue was purified by column chromatography
(
silica gel, 50–100% AcOEt–cC
yield: 53 mg (39%); mp 177–180 8C. H NMR (500 MHz,
DMSO-d ): = 2.01 (s, 3H, COCH ), 2.39–2.50 (m, 2 H, CH ),
.04 (m, 1 H, CHH), 3.82 (t, 1 H, J = 9.6 Hz, CHH), 5.76 (s, 1 H,
H-8a), 6.36 (s, 1 H), 7.22 (dd, 1 H, J = 2.4 Hz, J = 8.7 Hz),
.39 (d, 2 H, J = 9.0 Hz), 7.40 (s, 1 H), 7.54 (d, 2 H, J = 9.0 Hz),
6
H
12) to give a white solid;
3
d
1
110.99, 118.02, 120.50, 121.12, 127.75, 134.81, 137.73,
138.47, 144.96, 155.69, 156.40, 174.52. HRMS (ESI): m/z
6
d
3
2
3
[M+Na]+ calcd for
418.1745. X-ray analysis .
22 25 3 4
C H N O Na: 418.1743, found:
3
1
2
7
7
1
3
.89 (d, 1 H, J = 9.0 Hz), 8.87 (s, 1 H, CHO). C NMR
): = 22.11, 36.60, 46.42, 79.95, 84.72,
4.1.6. 1-Acetyl-3a,5-dihydroxy-N-(2-methoxyphenyl)-
2,3,3a,8a-tetrahydropyrrolo[2,3-b]indole-8(1H)-
carboxamide 14
(125 MHz, DMSO-d
6
d
1
1
16.44, 118.08, 119.97, 123.22, 126.68, 128.78, 135.21,
37.60, 138.29, 147.17, 151.76, 162.25, 170.19. HRMS
The residue was purified by column chromatography
(
ESI): m/z [M+Na]+ calcd for C20
H
18
N
3
O
5
ClNa: 438.0833,
(silica gel, 0–5% MeOH–Et
53 mg (26%); mp 161–164 8C. H NMR (500 MHz, CD
= 2.14 (s, 3 H, COCH ), 2.45 (m, 2 H, CH ), 3.08–3.13 (m, 1
H, CHH), 3.33–3.88 (m, 1 H, CHH), 3.88 (s, 3 H, OCH ), 5.81
2
O) to give a white solid; yield:
1
found: 438.0835.
3
OD):
d
3
2
4
.1.3. 1-Acetyl-8-formyl-3a-hydroxy-1,2,3,3a,8,8a-
3
hexahydropyrrolo[2,3-b]indol-5-yl (2-
(s, 1 H, H-8a), 6.80 (dd, 1 H, J
H, J = 2.5 Hz), 6.90 (td, 1 H, J
H, = 1.5 Hz, J = 8.0 Hz),
= 1.5 Hz, J = 8.0 Hz), 7.43 (d, 1 H, J = 8.5 Hz), 7.76 (dd, 1
H, J = 1.5 Hz, J
= 22.15, 37.65, 48.51, 56.49, 84.45, 87.33, 110.91, 112.31,
1
= 2.5 Hz, J
= 1.5 Hz, J
7.05
2
= 8.0 Hz), 6.86 (d, 1
= 8.0 Hz), 7.00 (dd,
nitrophenyl)carbamate 8
1
2
The residue was purified by column chromatography
silica gel, AcOEt) to give a yellow oil; yield: 13 mg (12%).
1
J
1
2
(td,
1
H,
OD):
(
J
1
2
1
13
H NMR (200 MHz, CDCl
m, 2 H, CH ), 3.14–3.28 (m, 1 H, CHH), 3.70–3.79 (m, 1 H,
CHH), 3.95 (br.s, 1 H, OH), 5.88 (s, 1 H, H-8a), 7.18–7.32
m, 3 H), 7.68 (t, 1 H, J = 7.8 Hz), 8.04 (d, 1 H, J = 8.4 Hz),
.27 (dd, 1 H, J = 1.6 Hz, J = 8.7 Hz), 8.51 (d, 1 H,
J = 7.6 Hz), 8.87 (s, 1 H, CHO). C NMR (50 MHz, CDCl
3
):
d
= 2.05 (s, 3 H, COCH
3
), 2.52
1
2
= 7.5 Hz).
C NMR (125 MHz, CD
3
(
2
d
118.00, 121.09, 121.62, 123.79, 125.46, 129.45, 135.00,
137.80, 152.63, 155.84, 157.08, 174.12. HRMS (ESI): m/z
(
8
1
2
1
[M+Na]+ calcd for
406.1378.
20 21 3 5
C H N O Na: 406.1379, found:
3
3
):
= 22.15, 37.12, 46.68, 80.20, 85.51, 117.30, 117.94,
20.80, 123.15, 123.89, 126.00, 133.96, 134.49, 136.06,
36.49, 138.98, 147.35, 151.39, 162.98, 170.62. HRMS
d
1
1
Acknowledgment
(
18 4 7
ESI): m/z [M+Na]+ calcd for C20H N O Na: 449.1073,
found: 449.1076.
We thank Krystyna Wojtasiewicz for her valuable
technical assistance.
4.1.4. 1-Acetyl-3a,5-dihydroxy-N-(2-isopropylphenyl)-
,3,3a,8a-tetrahydropyrrolo[2,3-b]indole-8(1H)-
2
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The residue was purified by column chromatography
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(
[
2
(
[
[