Complete assignments of 1H and 13C NMR spectral data for 7, 7'-dihydroarylnaphthalene lignan lactones

Article abstract of DOI:10.1002/mrc.2410

In this article we present a complete H and C NMR spectral analysis of three 7, 7'-dihydroarylnaphthalene lignan lactones using modern NMR techniques such as COSY, HSQC, HMBC and NOE experiments. Complete assignment and homonuclear hydrogen coupling const

Full text of DOI:10.1002/mrc.2410

Spectral Assignments and Reference Data
Received: 2 December 2008
Revised: 8 January 2009
Accepted: 14 January 2009
Published online in Wiley Interscience: 19 February 2009
(www.interscience.com) DOI 10.1002/mrc.2410
Complete assignments of 1H and 13C NMR
spectral data for 7,7ꢀ-dihydroarylnaphthalene
lignan lactones
a∗
a
˜
Rosangela da Silva, Joao Henrique Carvalho Batista,
Carine da Silva Maringoloa and Paulo Marcos Donateb
In this article we present a complete 1H and 13C NMR spectral analysis of three 7,7ꢀ-dihydroarylnaphthalene lignan lactones
using modern NMR techniques such as COSY, HSQC, HMBC and NOE experiments. Complete assignment and homonuclear
c
hydrogen coupling constant measurements were performed. Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Keywords: 1H NMR; 13C NMR; 2D NMR; apopicropodophyllin; 7,7ꢁ-dihydronaphthalene lignan lactone
Introduction
(500.13 MHz for 1H and 125.76 MHz for 13C) equipped with an
inverse probe head of 5 mm (BBI 1H-BB). The 1H NMR spectra
were acquired with an solar water heating (SWH) of 8.28 kHz,
TD of 64K, and NS of◦16, which provided a digital resolution
of ca 0.126 Hz (1H 30 pulse width = 8.5 µs). As for the 13C
NMR spectra, an SWH of 23.98 kHz was employed, with TD of
32K and NS of 1024, giving a digital resolution of ca 0.732 Hz
Lignan lactones are natural products that display several
biological properties and have several kinds of chemical
skeletons.[1] We have synthesized several natural and syn-
thetic products during our studies on the biological prop-
erties of these lignans. The structural elucidation of the
obtained compounds furnished important NMR data, which
contributed to the completion the spectroscopic data found
in the literature for several classes of lignan lactone
skeletons.[2–5]
In this article, we describe the spectrometric properties of lig-
nans in which there is a double bond in the C8–C8ꢁ position
(Fig. 1). Several lignans containing this type of skeleton were
obtained by total and partial synthesis, and we have selected
three among these substances to carry out a detailed NMR study.
Compounds 1 and 2 were obtained by total synthesis[6] from
butenolide 4 (Scheme 1), and β-apopicropodophyllin (3) was pre-
pared from the natural picropodophyllin[7] by partial synthesis
(Scheme 2).
(
13C 30◦ pulse width = 14.25 µs). DEPT (512 scans), 1H/1H
and 13C/1H 2D chemical shift correlation experiments were
carried out using standard pulse sequences supplied by the
spectrometer manufacturer. Long-range 13C/1H chemical shift
correlations were obtained in experiments with delay values
optimized for 2J(C,H) = 8 Hz. Experiments were performed
at 300 K and the concentrations for all samples were in the
range 10–15 mg ml−1 in CDCl3 or C6D6, using TMS as internal
reference.
Results and Discussion
Thus,inthisarticle,wepresentadetailedassignmentoftheNMR
data obtained for such 7,7ꢁ-dihydronaphthalene lignan lactones,
including the 2D NMR data.
In the case of the data initially acquired in CDCl3, the overlap
of several resonances precluded the assignment. Therefore,
C6D6 was used as solvent for all samples, which provided
much clearer spectra for 2, but not for 1 and 3. The 1H
NMR signals of 2 were resolved by using C6D6 as solvent,
which allowed verification of the multiplicities, observation
of the chemical shifts, and measurement of the coupling
constants.
Experimental
Materials
Lignans 1 and 2 were prepared from lactone 4,[7] as described
in Scheme 1, whereas lignan 3 was obtained by partial synthesis
from picropodophyllin,[7] as shown in Scheme 2.
∗
ˆ
Correspondence to: Rosangela da Silva, Nu´cleo de Ciencias Exatas e Tec-
´
nologicas, Universidade de Franca, Avenida Dr. Armando Salles de Oliveira,
201, 14404-600, Franca, SP, Brazil. E-mail: rosilva@unifran.br
NMR measurements
All 1-D (1H and 13C) NMR experiments were performed on a Bruker
Avance DRX400 spectrometer (400.13 MHz for 1H and 100.61 MHz
for 13C) equipped with a direct probe head of 5 mm (DUL 13C-
1). 2D and nuclear Overhauser effect (NOE) NMR experiments
were accomplished on a Bruker Avance DRX500 spectrometer
ˆ
´
a
Nu´cleo de Ciencias Exatas e Tecnologicas, Universidade de Franca, Avenida Dr.
Armando Salles de Oliveira, 201, 14404-600, Franca, SP, Brazil
ˆ
Departamento de Química da Faculdade de Filosofia, Ciencias e Letras de
RibeiraoPreto, UniversidadedeSaoPaulo, AvenidaBandeirantes, 3900, 14040-
901, Ribeirao Preto, SP, Brazil
b
˜
˜
˜
c
Magn. Reson. Chem. 2009, 47, 523–526
Copyright ꢀ 2009 John Wiley & Sons, Ltd.

da Silva et al.
Table 1. 1H and 13C NMR chemical shifts, υ (ppm), multiplicities and coupling constants, J(H–H) (Hz), 1H–1H and 1H–13C correlations in HMBC, COSY
and HMQC spectra for compound 1
C
δC (ppm)
H
δH (ppm)
Multiplicity
Coupling constant (Hz)
HMBC
COSY
HSQC
1ꢁ
2ꢁ
3ꢁ
4ꢁ
5ꢁ
6ꢁ
7ꢁ
130.1
108.5
147.8
147.3
108.3
121.6
42.2
–
2ꢁ
–
–
–
br s
–
–
–
–
–
6.52
–
–
C-1ꢁ,6ꢁ,7ꢁ
H-7ꢁ,6ꢁ
H-2ꢁ
–
–
–
–
–
–
–
–
–
–
H-6ꢁ
H-5ꢁ,7ꢁ
–
5ꢁ
6ꢁ
–
6.89
6.74
4.77
d
J(5 ,6 ) = 8.2
C-6ꢁ,1ꢁ,7ꢁ
H-5ꢁ
H-6ꢁ
H-7ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
br d
br s
J(6 ,5 ) = 8.2
C-5ꢁ,1ꢁ,2ꢁ
–
C-3,6ꢁ,8ꢁ,1,
H-7a,7b,9a,
9b,3,2ꢁ
1ꢁ,2,8,9
8ꢁ
9ꢁ
1
2
3
4
5
6
7
123.4
172.1
128.1
136.6
109,4
146.5
146.9
107.7
29.1
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
C-7ꢁ
–
H-7ꢁ,7a,7b,
–
–
3
6.70
–
s
H-3
–
–
–
–
–
–
–
–
–
–
6
6.60
3.87
s
C7,C1,C2
C-3,8ꢁ,1,2,
5,8, 9
C-3,8ꢁ,1,2,
5,8,9
H-7a,7b,
H-7ꢁ,6,3,
9a,9b,7ꢁ,6,3,9a,9b
H-6
H-7
7a
dd
J(7a,7b) = 22.3
J(7a,7 ) = 4.1
ꢁ
7b
3.65
dd
J(7b,7a) = 22.3
J(7b,7 ) = 4.3
ꢁ
8
9
157.0
71.0
–
–
–
d
d
s
–
–
–
–
9a
4.90
4.83
5.95
5.92
5.90
5.83
J(9a,9b) = 17.0
J(9b,9a) = 17.0
–
C-1,2,8,9
H-7ꢁ,7a,7b
H-9
9b
10
11
101.3
100.9
10a
10b
11a
11b
C-4,5
H-10b
H-10a
H-11b
H-11a
H-10a
H-10b
H-11a
H-11b
s
s
–
C-3ꢁ,4
s
OCH3
H3CO
R1
OCH3
H3CO
O
R1
O
O
O
CF3CO2H
LDA
OH
O
ArCHO
O
O
O
O
O
(4)
O
R1=H (2)
R1=OCH3 (3)
O
lactone
Scheme 1. Preparation of compounds 1 and 2.
Most of the 1HNMR signals for 1–3 are resolved. This allowed us
toverifythemultiplicities,observethechemicalshiftsandmeasure
the coupling constants in most cases. Most 13C signals could be
assigned through HMQC. For quaternary carbons, comparison
with calculated spectra9 and analysis of HMBC data were sufficient
to complete the assignment.
The position of aromatic ring in the C7ꢁ was confirmed by
Nuclear Overhauser Effect Difference (NOEDiff) experiments, with
irradiation at the frequencies corresponding to H7 and H9. The
most important results were the enhancement of the H9 signals
when irradiated at the H7 frequency, and the enhancement of
OCH
3
OCH
3
H CO
3
H CO
3
3
OCH
OCH
3
Ac2O
O
100°C
O
O
O
O
O
O
O
HO
picropodophyllin
(3)
Scheme 2.
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 523–526

1H and 13C NMR spectral data for 7,7ꢁ-dihydroarylnaphthalene lignan lactones
12
11
12
OCH3
O
11
OCH3
13
OCH3
4'
H3CO
11
O
H3CO
3'
5'
6'
2'
O
O
O
1'
3
8'
2
4
O
O
O
O
O
9'
7'
O
O
O
10
10
10
8
5
O
9
1
7
6
(1)
(2)
(3)
Figure 1. Structures of compounds 1, 2 and 3.
Table 2. 1H and 13C NMR chemical shifts, υ (ppm), multiplicities and coupling constants, J(H,H) (Hz), 1H–1H and 1H–13C correlations in HMBC, COSY
and HSQC spectra for compound 2, in C6D6 for 1H and in CDCl3 for 13C NMR
C
δC (ppm)
H
δH (ppm)
Multiplicity
Coupling constant (Hz)
HMBC
COSY
HMQC
1ꢁ
2ꢁ
3ꢁ
4ꢁ
5ꢁ
6ꢁ
130.1
112.0
147.8
147.3
111.2
120.2
–
2ꢁ
–
–
–
d
–
–
–
H-7
–
–
H-2ꢁ
–
7.00 (1H)
–
J(2 ,6 ) = 2.1
C-1ꢁ,6ꢁ,7ꢁ
ꢁ
ꢁ
–
–
–
–
–
–
–
–
–
–
5ꢁ
6ꢁ
6.55 (1H)
6.68 (1H)
d
J(5 ,6 ) = 8.2
C-6ꢁ,1ꢁ,7ꢁ
C-5ꢁ,1ꢁ,2ꢁ
H-6ꢁ
H-5ꢁ,7ꢁ
H-5ꢁ
H-6ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
dd
J(6 ,5 ) = 8.2
J(6 ,2 ) = 2.1
7ꢁ
42.1
7ꢁ
4.77 (1H)
brs
–
C-3,6ꢁ,8ꢁ,1,
1ꢁ,2,8,9
H-2ꢁ,6ꢁ
H-7ꢁ
8ꢁ
9ꢁ
1
2
3
4
5
6
7
123.7
172.3
128.3
135.4
107.7
146.7
146.1
109.5
29.2
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
H-6
–
–
5
6.63 (1H)
–
s
C 7ꢁ,2
H-3
–
–
–
–
–
–
–
–
–
–
2
6.43 (1H)
2.88 (1H)
s
C-7,1,2
C-3,8ꢁ,1,2,5,8,9
H-3,7,10
H-9
H-6
H-7
7a
dd
J(7a,7b) = 22.3;
J(7a,7 ) = 4.3
ꢁ
7b
2.50 (1H)
dd
J(7a,7b) = 22.3
C-3,8ꢁ,1,2,5,8,9
J(7a,7 ) = 4.0
ꢁ
8
9
157.0
71.0
–
–
–
d
d
s
–
–
–
–
9a
3.78 (1H)
3.73 (1H)
5.33 (1H)
J(9a,9b) = 16.8
C-1,2,8,9
H-7
H-9
9b
10a
10b
10
J(9b,9a ) = 16.8
ꢁ
10
101.2
–
H-10b
H-10a
H-10b
H-11
s
C-4,5
C-3ꢁ
C-4ꢁ
H-10a
11
12
55.8
55.8
3.48 (3H)
3.35 (3H)
s
–
–
–
–
11
s
H-12
the H7 signals when irradiated at the H9 frequency. Results are in
agreement with the structures shown in Fig. 1.
The 1H and 13C NMR data of compounds 1, 2 and β-
apopicropodophyllin(3)aregiveninTables 1,2and3,respectively.
cases. All results were confirmed by spectral simulations.[8] The
position of aromatic ring in the C7ꢁ was confirmed by NOEDiff
experiments.
Acknowledgements
Conclusion
The authors thank Fundac¸a˜o de Amparo a` Pesquisa do Estado
de Sa˜o Paulo (FAPESP), Coordenadoria de Aperfeic¸oamento de
Pessoal do Ensino Superior (CAPES) and Conselho Nacional de
Desenvolvimento Científico e Tecnolo´gico (CNPq) for financial
support.
The assignment of all hydrogen and carbon signals and the mea-
surement of all 1H/1H coupling constants were accomplished for
compounds 1, 2 and 3. The use of HMQC and COSY allowed deter-
mination of most of the chemical shifts and coupling constants.
HMBC and spectral simulations solved the more complicated
c
Magn. Reson. Chem. 2009, 47, 523–526
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

da Silva et al.
Table 3. 1H and 13C NMR chemical shifts, υ (ppm), multiplicities and coupling constants, J(H,H) (Hz), 1H–1H and 1H–13C correlations in HMBC, COSY
and HMQC spectra for compound 3, in CDCl3
C
δC (ppm)
H
δH (ppm)
Multiplicity
Coupling constant (Hz)
HMBC
gCOSY
HMQC
1ꢁ
2ꢁ
3ꢁ
4ꢁ
5ꢁ
6ꢁ
7ꢁ
8ꢁ
9ꢁ
1
136.9
105.6
153.1
147.2
153.2
105.7
42.7
–
2ꢁ (1H)
–
–
6.41
–
–
s
–
–
–
–
–
–
–
–
H-2ꢁ
–
C-3ꢁ,6ꢁ,1ꢁ,8ꢁ
H-7ꢁ
–
–
–
–
–
–
–
–
–
–
–
–
–
–
H-7ꢁ
H-3ꢁ,6ꢁ
–
6ꢁ (1H)
7ꢁ (1H)
–
6.41
4.83
–
s
C-4ꢁ,8ꢁ,2ꢁ,5ꢁ
H-6ꢁ
H-7ꢁ
–
m
–
–
–
–
–
–
–
–
–
–
C-3,6ꢁ,2ꢁ,8ꢁ,
128.1
172.2
129.6
123.7
109.5
140.6
147.0
107.7
29.2
–
–
–
–
–
–
–
–
–
–
–
–
–
–
2
–
–
–
–
C-7ꢁ,2,1
–
–
H-6
–
–
3
3 (1H)
–
6.62
–
s
H-3
–
4
–
5
–
–
–
–
–
–
6
6 (1H)
7a (1H)
7b (1H)
–
6.70
3.82
3.64
–
s
C-5,1,2,7
C-2,8ꢁ,6
H-3,7,10
H-9
H-6
H-7
7
dd
dd
–
J7a7b = 27.9;J7a,7 = 2.5
ꢁ
ꢁ
J7b7a = 27.9;J7b,7 = 3.5
8
9
157.3
71.1
–
–
–
–
–
9a (1H)
9b (1H)
10a (1H)
10b (1H)
11 (3H)
12 (3H)
13 (3H)
4.87
4.82
5.93
5.90
3.76
3.79
3.76
m
m
d
d
s
C-8ꢁ,1,8,9ꢁ
H-7
H-9a
H-9b
H-10a
H-10b
H-11
H-12
H-13
10
101.3
J10a,10b = 4.5
C-4,5
H-10b
J10b,10a = 4.5
H-10a
11
12
13
56.1
60.7
56.1
–
–
–
C-3ꢁ
C-4ꢁ
C-5ꢁ
–
–
–
s
s
References
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 523–526