NMR studies of pyrimidinic nucleosides derived from 2,3-dideoxy-d-ribose with inhibitory activity on LINE-1 mobility

Full text of DOI:10.1002/mrc.4942

Received: 7 June 2019
DOI: 10.1002/mrc.4942
Revised: 17 September 2019
Accepted: 17 September 2019
L E T T E R ‐ S P E C T R A L A S S I G N M E N T
NMR studies of pyrimidinic nucleosides derived from
2,3‐dideoxy‐D‐ribose with inhibitory activity on LINE‐1
mobility
1 | INTRODUCTION
2 | RESULTS AND DISCUSSION
1
In this work, the signals of the H and 13C NMR spectra
Pyrimidine nucleoside analogues possess a high pharma-
cological interest. They show a highly useful antiviral
activity against VIH, hepatitis B virus,[1–3] and anticancer
activity[4] and are currently used for the treatment of
these diseases. Given its importance, many scientists have
modified the structure of these nucleoside analogues
seeking to improve their properties, target specificity, effi-
cacy, and to decrease its toxicity.[5,6] As a consequence of
this research, some analogues have been described with
improved properties,[7] among which are nucleosides
derived from 2,3‐dideoxy‐D‐ribose such as Zidovudine
(AZT), Didanosine (ddI), and Zalcitabine (ddC). Many
researchers have also studied the NMRs spectra of these
compounds. Particularly, they have described the influ-
of unprotected nucleosides 1–18 (Figure 1) and their pre-
cursors 19–36 (Figure 2) are fully assigned on the basis of
1H chemical shifts, coupling constants, and 13C chemical
shifts, together with two‐dimensional H‐1H (COSY) and
1
1H‐13C spectra (HSQC and HMBC). The assignment of
the stereochemistry of the anomeric centres are also
described here based on 1H NMR or 1D‐NOE experi-
ments. The H and 13C NMR chemical shifts values for
1
compounds 1–36 are provided in Tables 1–4.
The configuration of the anomeric centre was initially
established by 1D‐NOE interactions either of the TBDMS‐
protected or final nucleosides, except for compounds 1, 2,
and 13–16 whose configurations were established by com-
paring their NMR data with the previously published
results (see Tables 1 and 3 for specific references).
Regarding the 1D‐NOE experiments, for trans‐
nucleosides, the NOE interaction between H‐1′ and H‐5′
was sought to support the structure of the α‐anomer. In
the cases were the 1D‐NOE spectra lacked positive signals
between H‐1′ and H‐5′, positive interactions between H‐
4′ and H‐6 were used to sustain the presence of the α‐
anomer. Similarly, the configuration of cis‐nucleosides
was established through 1D‐NOE coupling between H‐1′
and H‐4′, and when this interaction was not observed,
1D‐NOE coupling between H‐5′ and H‐6 was used to
establish the β configuration. The 1D‐NOE interactions
for α‐anomers and β‐anomers are shown in Figure 3.
As for the configuration of the anomeric carbon (C‐1′)
on compounds 1–36, the influence of its stereochemistry
in the chemical shifts of specific hydrogens in the mole-
cules is particularly important and is maintained in all
2′,3′‐dideoxynucleoside analogues synthesized in this
study. This effect have been previously used to identify
the two possible anomers in nucleosides[11,12] and con-
1
ence of the anomeric configuration on the H and 13C
NMR signals in compounds like, for example, adenosine
nucleosides[8] or in isonucleosides.[9]
As part of our research in the inhibition of transpos-
able element such as LINE‐1, we have synthesized
(Scheme 1) 18 nucleoside analogues of 2′,3′‐
dideoxyribonucleosidic nature (compounds 1–18,
Figure 1) as well as their corresponding precursors (com-
pounds 19–36, Figure 2) and assayed 1–18 against mam-
malian LINE‐1 retrotransposition with very interesting
and promising results.[10] While some of these com-
pounds have already been describe in the literature (vide
infra), others have been recently synthesize by us, and
their minimal NMR data described in Reference 10. Here
in this work, we describe the complete 1H and 13C signals
assignment of these 36 nucleosides having pyrimidine, 5‐
aza‐pyrimidine, and 6‐aza‐pyrimidine bases with 2,3‐
dideoxy‐D‐ribose, both 5′‐O‐protected and unprotected
(1–36), by means of its 2‐D spectra as well as 1D‐NOE
experiments. In addition, and as previously reported by
Okabe[11] and Lin,[12] we show a pattern in the 1H chem-
ical shifts that allows the assignment of the α‐ and β‐
anomeric configuration based on 1‐D 1H NMR and
without the need of further and more specific NMR
experiments.
1
sists on a notable difference in the H chemical shifts of
positions 4′, 5′, and 6 for α‐ and β‐anomers. It offers an
easy approach to assign the anomeric configuration in
nucleosides, and we have applied it to the compounds
Magn Reson Chem. 2019;1–8.
wileyonlinelibrary.com/journal/mrc
© 2019 John Wiley & Sons, Ltd.
1

2
LETTER ‐ SPECTRAL ASSIGNMENT
described in this study. The significant trails to look for
are the deshielding of the H‐4′ signal in the α‐anomers
(trans isomer) when compared to the β‐anomers (cis iso-
mer), and the deshielding of H‐6 and H‐5′ signals in the
β‐anomers when compared to the α‐anomers. Applied to
the nucleoside analogues on this study, compounds 1–
18, it can be seen that all H‐6 and H‐5′ chemical shifts
of β‐anomers (cis isomer) are higher than those of α‐
anomer (trans isomer), whereas H‐4′ chemical shifts are
lower in β‐anomers (see Table 5). As an illustrating exam-
ple, the chemical shift of H‐4′ in compound 2 (β‐anomer)
is 0.27 ppm lower than the same H‐4′ proton in com-
pound 1 (α‐anomer). Also as predicted, the chemicals
shifts of H‐5′ and H‐6′ protons in compound 2 (β‐
anomer) are 0.25, 0.16, and 0.42 ppm higher, respectively,
than in compound 1 (α‐anomer). This trend is repeated in
compounds 1–18, and the results match the predicted
effects and validating the initially 1D‐NOE‐assigned
anomeric configurations.
SCHEME
1
General synthesis of 2′,3′‐dideoxynucleoside
analogues. A: 1) NaNO2, HCl·H2O, 16 hr, 0°C to rt; 2) BH3·SMe2,
THF, 3 hr, 0°C to rt; 3) tert‐Butyldimethylsilyl chloride, imidazole,
DCM, 3 hr, 0°C to rt; B: 1) DIBAL‐H, toluene, 2 hr, −75°C; 2) Ac2O,
TEA, 16 hr, 0°C to rt; 3) Silylated nitrogenous base, EtAlCl2, 1,2‐
DCE, 16 hr, 0°C to rt; C: Tetra‐n‐butylammonium fluoride 1 M in
THF, THF, 15 min, 0°C. NB: Nitrogenous base
One possible explanation for the above results has
been given[25,26] and is based on the presence of an H‐
bond between H‐6 and the hydroxyl group in β‐nucleo-
side analogues. This interaction has been reported in
crystallographic studies,[27–30] although later research
has proven that crystallographic data might not accu-
rately represent the solution‐phase conformations and
intramolecular hydrogen‐bonding that can take place
in solution.[26,31] On the other hand, computational
studies sustain that the H(6)─OH H‐bond can take
place in solution when nucleosides acquire the anti‐
conformation[25,26] (anti referring to the position of the
carbonyl group at C‐2 in relation to the sugar ring)
and suggest that this bond would explain the
deshielding effect observed by H‐6 in the β‐anomer.[32–34]
Moreover, another experimental fact that sustains
the presence of the H(6)─OH H‐bond has been
FIGURE 1 Structures of nucleoside analogues
FIGURE 2 Structures of 5′‐O‐silyl
protected nucleoside analogues

LETTER ‐ SPECTRAL ASSIGNMENT
3

4
LETTER ‐ SPECTRAL ASSIGNMENT
TABLE 2 Assignment of 13C signals from nucleosides
Compound C2
C4
C5
C6
C1′ C2′ C3′ C4′ C5′
1
150.4
163.4
163.3
163.7
164.0
156.2
155.4
159.2
161.8
161.7
161.8
102.3
102.1
110.9
110.7
135.7
135.8
96.7
139.5
140.6
135.2
136.4
87.7 32.9 25.9 82.1 64.8
86.7 32.7 25.1 81.7 63.5
87.2 32.7 26.1 81.8 64.9
86.3 32.2 25.3 81.3 63.6
87.3 30.0 26.5 81.9 64.7
87.2 31.0 26.1 82.4 64.8
88.2 33.1 25.7 82.3 64.7
88.3 34.0 25.2 84.0 63.0
89.6 33.4 26.7 83.6 65.1
88.2 34.0 25.2 83.9 63.0
2
150.3
150.3
150.5
148.3
147.6
149.6
151.6
151.3
151.3
150.7
150.8
3
4
5
6
7
139.1
142.4
138.9
139.8
8
96.2
9
109.1
108.6
10
11
12
13
14
15
16
17
18
159.6 (d, J4,F = 26.0 Hz) 141.8 (d, J5,F = 232.7 Hz) 126.0 (d, J6,F = 34.3 Hz) 89.1 33.2 26.7 83.4 65.1
159.7 (d, J4,F = 26.1 Hz) 141.5 (d, J5,F = 231.3 Hz) 126.6 (d, J6,F = 35.0 Hz) 87.9 33.7 25.4 83.7 63.3
158.05 167.56
95.6
95.2
142.1
142.8
89.7 33.8 26.5 83.4 65.2
88.4 34.1 25.7 83.6 63.7
158.3
156.5
156.5
167.6
159.6 (d, J4,F = 13.9 Hz) 138.4 (d, J5,F = 242.0 Hz) 126.2 (d, J6,F = 32.4 Hz) 89.8 33.8 26.5 83.4 65.2
159.5 (d, J4,F = 14.1 Hz) 138.2 (d, J5,F = 240.7 Hz) 127.2 (d, J6,F = 33.3 Hz) 88.6 34.3 25.1 83.9 63.2
156.59 168.2
156.6 168.0
156.6
157.4
90.1 33.7 26.4 83.7 65.1
88.8 34.3 25.0 84.4 63.1
Note: Signals belonging to the methyl group in thymidine derivatives are not included. Spectra were recorded as follows: for compounds 1–5 and 7 with a
500 MHz spectrometer using CDCl3 as solvent; for 6, 600 MHz and CDCl3; for 8, 600 MHz and CD3OD; for compounds 9, and 11–17, 500 MHz and CD3OD;
for 10, 400 MHz and CD3OD; for 18, 500 MHz and D2O.
proposed.[35] In β‐anomers, the chemical shifts of 5′
hydrogens are affected by the H(6)─OH H‐bond.
Because of this H‐bond, the rotation of the C‐4′─C‐5′
experiments, the employed parameters were the follow-
ing: pulse width (135°), 9.0 ms; recycle time, 1 s; 0.5 J
(CH) = 4 ms; 65,536 data points acquired and trans-
formed from 1,024 scans; spectral width, 15 KHz; and
line broadening, 1.3 Hz. Chemical shifts (δ) are quoted
in parts per million (ppm) and are referenced to the
residual solvent peak. Spin multiplicities are given as s
(singlet), bs (broad singlet), d (doublet), dd (doublet of
doublet), ddd (doublet of doublet of doublet), td (triplet
of doublet), t (triplet), tt (triplet of triplet), q (quadru-
plet), and m (multiplet). Coupling constants (J) are given
in Hertz.
1
bond is restrained making the H chemical shifts of 5′
hydrogens apart from each other as a consequence of
this lack of rotation. In summary, the effect described
above can be observed in all 2′,3′‐dideoxynucleoside
analogues (1–18) synthesized in this study (Table 6),
sustaining once again the initially assigned configuration
of α‐ and β‐anomers and therefore allowing an easy and
fast stereochemistry prediction of the anomeric carbon
1
with a simple H NMR and without the need of extra
NMR experiments.
The heteronuclear single‐quantum correlation (HSQC)
spectra were calculated with a pulse sequence gc2hsqcse
(standard sequence, Agilent Vnmrj_3.2A software).
Nuclear Overhauser spectra were recorded on an Agilent
Varian Direct Drive spectrometer, operating at 500 MHz,
with a spectral width of 8.01 KHz at 16 K complex points
(acquisition time = 2 s). The mixing time in one‐
dimensional nuclear Overhauser spectroscopy (NOESY)
experiment was 0.5 s. Data processing with zero filling
at 64 K and apodization with exponential function (Line
Broadening [LB] = 0.5 Hz).
3 | EXPERIMENTAL
3.1 | NMR spectra
1
NMR spectra were made on 400‐MHz H NMR and 101‐
MHz 13C NMR Agilent Varian Direct Drive, on 300‐MHz
1H NMR and 75 MHz 13C NMR Varian Inova and 500‐
1
MHz H NMR and 125‐MHz 13C NMR Agilent Varian
Innova Unity spectrometers at 298 K. In DEPT

LETTER ‐ SPECTRAL ASSIGNMENT
5

6
LETTER ‐ SPECTRAL ASSIGNMENT
TABLE 4 Assignment of 13C signals from 5′‐O‐silyl protected nucleosides
Compound C2
150.3 163.6
150 163.8
C4
C5
C6
C1′ C2′ C3′ C4′ C5′
88.1 32.9 25.8 82.2 65.4
86.4 33.6 24.4 82.2 63.7
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
101.9
101.5
110.4
110.3
135.4
135.3
96.3
139.4
140.7
135.3
135.8
150.2 163.9
150.5 164.1
147.8 155.9
147.8 155.7
149.5 159.1
149.9 159.4
149.3 159.1
149.5 159.1
87.5 32.8 26
81.9 65.4
85.9 32.7 25.5 81.1 64.6
87.7 30.3 26.8 81.9 65.5
86.8 30.1 27.4 82.3 65.6
88.7 33.2 25.6 82.4 65.3
139.1
139.8
136.5
137.4
96.4
87
88.6 33.1 25.6 82.4 65.3
87 33.4 24.9 82 64.3
33.2 25
81.9 64.4
108.7
108.6
148.9 157.2 (d, J4, F = 26.6 Hz) 140.5 (d, J5, F = 236.9 Hz) 123.8 (d, J6, F = 33.7 Hz) 88.2 32.9 25.7 82.3 65.3
148.9 157.1 (d, J4,F = 27.1 Hz) 140.3 (d, J5,F = 235.5 Hz) 125 (d, J6,F = 34.3 Hz) 86.7 33.6 24.4 82.3 63.9
156.1 166
93.8
93.3
140.3
141.8
88.7 33
25.5 82
65.5
156.1 165.9
87.1 33.9 26
82.2 63.7
154
158.1 (d, J4,F = 13.5 Hz) 136.5 (d, J5,F = 240.9 Hz) 124.7 (d, J6,F = 31.8 Hz) 88.8 33
25.5 82.2 65.4
154.1 157.9 (d, J4,F = 13.7 Hz) 136.3 (d, J5,F = 239.0 Hz) 126.3 (d, J6,F = 32.2 Hz) 87.2 33.8 24
82.5 63.6
154
166.6
154.8
156.2
89.1 33.1 25.3 82.5 65.3
87.5 33.9 23.9 82.9 63.4
154.3 166.6
Note: Signals belonging to the silyl protective group (TBDMS‐) and methyl group in thymidine derivatives are not included. All spectra were recorded in a 500‐
MHz spectrometer using CDCl3 as solvent.
TABLE 5 Shielding differences between α‐ and β‐anomers of
compounds 1–18
Comparison between
β‐ and α‐nucleosides
H‐4′
H‐5′
H‐6
2(β) vs 1(α)
4 vs 3
−0.27
−0.31
−0.17
−0.35
−0.31
−0.34
−0.32
−0.33
−0.2
+0.25/+0.16
+0.23/+0.15
+0.09/+0.08
+0.14/+0.08
+0.29/+0.17
+0.27/+0.16
+0.24/+0.15
+0.29/+0.17
+0.28/+0.22
+0.42
+0.37
6 vs 5
8 vs 7
+0.97
+0.69
+0.59
+0.44
+0.62
+0.37
FIGURE 3 NOE interactions for α‐anomers and β‐anomers used
to determine the anomeric configuration in the nucleoside
analogues
10 vs 9
12 vs 11
14 vs 13
16 vs 15
18 vs 17
3.2 | Procedure a
3.2.1 | Synthesis of (S)‐γ‐[[(tert‐
butyldimethylsilyl)oxy]methyl]‐y‐
butyrolactone
overnight. The solvent was coevaporated with toluene
under vacuum below 40°C. The residue was dissolved in
MeOH and stirred with 2 g of Dowex 50WX8 for 2 hr in
order to remove unreacted L‐glutamic acid. Solids were
filtered out, washed with MeOH, and concentrated under
vacuum to afford (S)‐γ‐butyrolactone‐γ‐carboxylic acid as
a crystalline solid, which was used in the next step with-
out further purification.
An aqueous solution of NaNO2 (5.2 g, 75.4 mmol in
7.2 ml of water) and 12.5 ml of 5.6 N HCl were simulta-
neously added dropwise with pressure‐equalizing
dropping funnels to a suspension of L‐glutamic acid
(7.35 g, 50 mmol) in 25 ml of water over 2 hr. While
adding solutions, reaction mixture was kept at 0°C and
then allowed to reach room temperature and stirred
BH3·SMe2 (9.2 ml, 92.24 mmol) was added, at
1 ml/10 min approximately, under Ar atmosphere to a

LETTER ‐ SPECTRAL ASSIGNMENT
7
TABLE 6 Chemical shift distances (ppm) between 5′ protons in α‐ and β‐anomers
1–2
3–4
5–6
7–8
9–10
11–12
13–14
15–16
17–18
α (trans)
β (cis)
0.18
0.27
0.18
0.26
0.21
0.24
0.19
0.25
0.12
0.24
0.12
0.23
0.09
0.18
0.11
0.23
0.11
0.17
Download link for NMR data:
https://figshare.com/s/2f916f1f1d89aa98a71d
solution of (S)‐γ‐butyrolactone‐γ‐carboxylic acid (8 g,
61.49 mmol) in anhydrous THF (40 ml). During the addi-
tion, reaction was cooled with an ice bath, then allowed
to reach room temperature and stirred overnight. MeOH
was carefully added to quench the reaction and the sol-
vent was removed under vacuum. MeOH was added
and evaporated twice, and the residue was finally dried
by coevaporation with toluene twice, obtaining (S)‐γ‐
(hydroxymethyl)‐γ‐butyrolactone as a pale yellow syrup
that was used without further purification.
added and stirred for 30 min. The mixture was extracted
with DCM, dried over Mg2SO4, and evaporated under
vacuum. Purification through FCC with hexane/diethyl
ether (95:5 + 1% TEA) led to the obtaining of the mixture
of anomers 1‐O‐acetyl‐5‐(tert‐butyldimethylsilyl)‐2,3‐D‐
dideoxy‐ribofuranose (400 mg, 67%) as a colourless syrup.
A mixture of the nitrogenous base (0.73 mmol), HMDS
(1.5 ml, 7.30 mmol), and (NH4)2SO4 (cat.) was refluxed
during 2 hr until a clear solution was obtained. The reac-
tion mixture was cooled and evaporated in vacuum. The
residue was dissolved in dry 1,2‐dichloroethane (3 ml),
under argon atmosphere, and a solution of 1‐O‐acetyl‐5‐
(tert‐butyldimethylsilyl)‐2,3‐D‐dideoxy‐ribofuranose
(100 mg, 0.36 mmol) in dry 1,2‐dichloroethane (2 ml) was
added. The reaction mixture was cooled in an ice bath,
treated with EtAlCl2 in toluene (1.8 M in toluene,
222 μl, 0.4 mmol), and allowed to stir for 16 hr at room
temperature. The reaction was then quenched with satu-
rated aqueous NaHCO3 solution and partitioned between
DCM and water. The organic layer was dried over
Mg2SO4, filtered, and concentrated. The residue was ini-
tially purified by FCC to obtain a mixture of isomeric
nucleosides that was next separated by preparative thin
layer chromatography on a glass plate. The silica was
scraped off and percolated through a pad of silica gel
using DCM/MeOH (90:10).
(S)‐γ‐(Hydroxymethyl)‐γ‐butyrolactone
(9.7
g,
83.54 mmol) was dissolved in DCM (50 ml) followed by
the addition of imidazole (7.5 g, 110.16 mmol). Reaction
mixture was cooled with an ice bath and tert‐
Butyldimethylsilyl chloride (15.11 g, 100.24 mmol) was
then added. The mixture was stirred overnight, letting it
to slowly reach room temperature. The reaction was
partitioned between water and DCM, and the organic
layer was dried over Mg2SO4 and concentrated. Through
FCC, using hexane/diethyl ether (9:1), (S)‐γ‐[[(tert‐
butyldimethylsilyl)oxy]methyl]‐y‐butyrolactone
was
obtained (10.7 g, 48% from L‐glutamic acid) as a
colourless syrup.
3.3 | Procedure B
3.3.1 | General procedure for sugar‐base
coupling
3.4 | Procedure C
To
a solution of (S)‐γ‐[[(tert‐butyldimethylsilyl)oxy]
3.4.1 | General procedure for the
methyl]‐γ‐butyrolactone (500 mg, 2.17 mmol) in anhy-
drous DCM (10 ml) at −78°C, 1 M solution of DIBAL‐H
in toluene (3.26 mL, 3.26 mmol) was added dropwise
(10 min approximately) under Ar atmosphere. The reac-
tion mixture was then stirred for an additional 45 min
at −78°C, after which a solution of DMAP (265 mg,
2.17 mmol) in 4 ml of DCM, TEA (907 μl, 6.5 mmol)
and Ac2O (1,026 μl, 10.85 mmol) were added. The reac-
tion was stirred overnight allowing it to slowly reach
room temperature and then a saturated aqueous solution
of sodium potassium tartaric acid (4 ml) and a saturated
aqueous solution of ammonium chloride (4 ml) were
desilylation of protected nucleosides
Each protected nucleoside (1.0 equiv) was dissolved in
THF and treated with tetra‐n‐butylammonium fluoride
(1 M in THF, 1.5 equiv). After stirring during 15–
30 min, the solvent was evaporated under reduced pres-
sure. The residue was dissolved in water and passed
through a C8 SPE (Sulpelco, bed wt. 500 mg, volume
3 ml) eluting with water. Each tube was analysed with
an LC–MS instrument in order to collect those tubes con-
taining the unprotected nucleoside and lacking
tetrabutylammonium salts.

8
LETTER ‐ SPECTRAL ASSIGNMENT
[11] M. Okabe, R. C. Sun, S. Y. K. Tam, L. J. Todaro, D. L. Coffen,
ACKNOWLEDGEMENT
J. Org. Chem. 1988, 53, 4780.
This work was partially supported by Junta de Andalucía
(Project CS2016.6). The authors also thank “Centro de
Instrumentation Científica” (CIC; Universidad de
Granada, Spain) for providing the NMR equipment.
[12] T.‐S. Lin, M.‐Z. Luo, M.‐C. Liu, Tetrahedron 1995, 51, 1055.
[13] H. Kawakami, T. Ebata, K. Koseki, K. Matsumoto, H.
Matsushita, Y. Naoi, K. Itoh, Heterocycles 1990, 31, 2041.
[14] K. E. Pfitzner, J. G. Moffatt, J. Org. Chem. 1964, 29, 1508.
[15] K. Agyei‐Aye, D. C. Baker, Carbohydr. Res. 1988, 183, 261.
[16] A. M. Michelson, A. R. Todd, J. Chem. Soc. 1955, 0, 816.
[17] A. Rosowsky, N. N. Pai, Nucleos. Nucleot. 1991, 10, 837.
ORCID
Guillermo Banuelos‐Sanchez
https://orcid.org/0000-0002-
[18] Y. Furukawa, Y. Yoshioka, K. Imai, M. Honjo, Chem. Pharm.
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9485-8168
Francisco Franco‐Montalban https://orcid.org/0000-0001-
6539-1653
[19] R. A. Zhuk, A. É. Berzinya, V. N. Silinya, É. É. Liepin'sh, S. A.
Giller, Chem. Heterocycl. Comp. 1979, 15, 926.
Juan A. Tamayo https://orcid.org/0000-0002-1037-8133
[20] T. A. Khwaja, C. Heidelberger, J. Med. Chem. 1967, 10, 1066.
[21] J. P. Horwitz, J. Chua, M. Noel, J. T. Donatti, J. Org. Chem.
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Guillermo Banuelos‐Sanchez
Francisco Franco‐Montalban
[22] C. H. Kim, V. E. Marquez, S. Broder, H. Mitsuya, J. S. Driscoll,
Juan A. Tamayo
J. Med. Chem. 1987, 30, 862.
Department of Medicinal and Organic Chemistry, Faculty
of Pharmacy, University of Granada, Granada, Spain
[23] K. Mitsudo, T. Kawaguchi, S. Miyahara, W. Matsuda, M.
Kuroboshi, H. Tanaka, Org. Lett. 2005, 7, 4649.
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Correspondence
Juan A. Tamayo, Department of Medicinal and Organic
Chemistry Faculty of Pharmacy, University of Granada,
Campus de Cartuja s/n. Granada 18071, Spain.
Email: jtamayo@ugr.es
[25] M. A. Palafox, Phys. Chem. Chem. Phys. 2014, 16, 24763.
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