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Letter - spectral assignment
Received: 17 December 2015
Revised: 30 March 2016
Accepted: 31 March 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/mrc.4442
1
13
H and C NMR spectral data of
p-nitrobenzenesulfonamides and
dansylsulfonamides derived from N-alkylated
o-(purinemethyl)anilines
Fátima Morales, Joaquín M. Campos and Ana Conejo-García*
(135°), 9.0ms; recycle time, 1 s; 1/2J (CH)= 4 ms; 65 536 data points
acquired and transformed from 1024 scans; spectral width, 15 KHz;
Introduction
In recent years, purine bases have been the subject of extensive
research that led to the discovery of thousands of biological active
compounds, including antineoplastic ones.[1–6] We synthesized a
novel series of alkylated purines (1-9) with notable in vitro anti-
proliferative activities, low toxicity and systemic distribution after
oral administration in vivo.[1] The design of these compounds was
based on the modifications of acyclic O,N-acetals, previously
described by our research group as anti-proliferative agents.[7–10]
We have also prepared the 5-fluorouracil (5-FU) derivative (10) as
a prototype compound. Finally, the fluorescent analogous (11-14)
of the most active compounds were synthesized in order to
study the in vitro and in vivo drug distributions.[1] The p-
nitrobenzenesulfonyl group was interchanged with the dansyl
group as a chromophore because of its similarity. Moreover, a
fluorescence study of some anti-tumour drugs with a dansyl
[5-(dimethylamino)naphthalene-1-sulfonyl] group in their struc-
ture that present no toxicity in vivo[11] confirms the use of this
chromophore in the design.
Although the structure of these derivatives was determined
by means of standard spectroscopic techniques (1H, 13C NMR
and MS), a detailed NMR study has been performed in order
to unequivocally corroborate their structures. Herein, we report
the 1H and 13C NMR unequivocal assignments of a series of
anti-proliferative compounds. The spectra of the precursors
and intermediate derivatives of the synthesis pathway for their
preparation are also included.
and line broadening, 1.3Hz. HMBC spectra were measured with a
pulse sequence gc2hmbc (Standard sequence, Agilent Vnmrj_3.2A
software) optimized for 8 Hz (inter-pulse delay for the evolution of
long-range couplings: 62.5ms). The HSQC spectra were measured
with a pulse sequence gc2hsqcse (Standard sequence Agilent
Vnmrj_3.2A software).
Results and discussion
The N-9-substituted derivatives (isomers 1-8, 11, 13; Scheme 1) and
the N-1-5-FU derivative 10 (Scheme 1) were obtained by
microwave-assisted Mitsunobu reaction as previously reported.[1]
We were also able to isolate the N-3-adenine derivative 9
(Scheme 1) and the N-7-2,6-dichloropurine derivatives 12 and 14
(Scheme 1).[1] By-products 19 and 20 (Scheme 1) were also
obtained when compounds 15 and 16 were treated with
tetrabutylammonium fluoride.
1H NMR and 13C NMR data (chemical shifts, multiplicity and
coupling constants) for compounds 1-25 are shown in
Tables 1–14. Unambiguous assignments for all NMR signals
were made through the combined information of one-
dimensional and two-dimensional NMR experiments such as
DEPT, HSQC and HMBC (see Supporting information).
The procedure used to determine the structures of 1-25 from
their NMR data is as follows: The identification of N-9-substituted
derivatives 1-7 relies on the observation of the correlation of the
benzylic hydrogen atoms linked to the purine with the C-4 of the
purine moiety in the HMBC spectrum. The C-4 of the purine moiety
(C-4pur) can be identified because of its 1,3-relationship with the
benzylic hydrogen atoms in 1-7 and in addition the H-2 atom of
the purine ring in 1, 2, 4-6 (Fig. 1).
Experimental
NMR spectroscopy was carried out at the Centro de
Instrumentación Científica, Universidad de Granada (Spain), and
the data were recorded at 400 MHz (1H) and 100 MHz (13C) on a
Varian NMR System 400, or at 300 MHz (1H) and 75MHz (13C) on a
Varian Inova spectrometer at ambient temperature. Chemical shifts
(δ) are quoted in ppm and are referenced to the residual solvent
peak. Spin multiplicities are given as s (singlet), d (doublet), dd
(double doublet), ddd (double double doublet), pst (pseudotriplet),
t (triplet) and m (multiplet). Coupling constants (J) are given in Hz.
The digital resolution of all 13C spectra recorded is 0.9536 Hz/points.
The following parameters were used in DEPT experiments: PW
The link between the benzylic hydrogen atoms and the quater-
nary carbons of the 2,6-dichloropurine moiety C-4pur and C-5pur
*
Correspondence to: Ana Conejo-García, Department of Pharmaceutical and
Organic Chemistry, Faculty of Pharmacy, University of Granada, c/ Campus de
Cartuja s/n, 18071 Granada, Spain. E-mail: aconejo@ugr.es
Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy,
University of Granada, c/ Campus de Cartuja s/n, Granada, Spain
Magn. Reson. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.