Letter - spectral assignment
Received: 17 September 2015
Revised: 22 October 2015
Accepted: 29 October 2015
Published online in Wiley Online Library: 23 November 2015
(wileyonlinelibrary.com) DOI 10.1002/mrc.4388
1
13
H and C NMR spectral assignments of novel
flavonoids bearing benzothiazepine
Seunghyun Ahn,a† Soon Young Shin,b† Yearam Jung,a Hyeryoung Jung,a
Beom Soo Kim,a Dongsoo Kohc** and Yoongho Lima*
The resulting solid was filtered and washed with ethanol and was
recrystallized from ethanol to form the pure benzothiazepine com-
Introduction
Benzothiazepine is a heterocyclic compound containing nitrogen
and sulfur. A variety of derivatives can be designed by modifying
the positions of the double bond and benzene ring. 2,3-Dihydro-
1,5-benzothiazepine (also known as 2,3-dihydro[b][1,4]thiazepine)
derivatives show diverse biological activities, including inhibitory
effects on alpha-glucosidase, urease, cholinesterase, and butyryl-
cholinesterase, and agonistic activity toward the transient receptor
potential ankyrin 1 (TRPA1) receptor (Fig. 1(A)).[1–4] When two ben-
zene rings are attached at the C-2 and C-4 positions, 2,4-diphenyl-
2,3-dihydro-1,5-benzothiazepine containing a C6-C3-C6 skeleton
can be derived (Fig. 1(B)). Flavonoids are found in various plants
as their secondary metabolites and are composed of C6-C3-C6 skel-
etons (Fig. 1(C)).[5,6] Because methoxylation and naphthalenyl
groups can increase cellular compartmentation and cell permea-
bility,[7,8] we designed and synthesized methoxylated 4-(1-hy-
droxy-naphthalen-2-yl)-2-phenyl-2,3-dihydro-1,5-benzothiazepine
derivatives (Fig. 1(D)). However, flavonoids bearing a benzo-
thiazepine skeleton have rarely been reported,[2,3] even though
their design and synthesis are of interest because of their biological
diversity. Furthermore, because the 1H and 13C NMR, and high res-
olution mass spectrometric (HR/MS) data can be used as references
for further study, herein, we report the NMR and MS data of 27
novel flavonoids bearing benzothiazepine skeletons.
pound (20, yield: 67%, MP: 213–221 °C).
NMR spectra
The synthesized benzothiazepines were prepared in deuterated chlo-
roform (CDCl3), apart from derivative 27, which was dissolved in deu-
terated dimethyl sulfoxide (DMSO-d6), with concentrations of
approximately 50 mM, and transferred into 2.5 mm NMR tubes for
the NMR experiments. All NMR spectroscopic data were collected
using an Avance 400 spectrometer (9.4 T; Bruker, Karlsruhe, Germany)
at room temperature. The chemical shifts were referenced to TMS.
The parameters for the 1H and 13C NMR experiments were as follows:
the relaxation delay, 90° pulse, spectral width, number of data points,
and digital resolution were set to 1 and 3 s, 11.8 and 15.0 μs, 5500 and
20 000 Hz, 32 and 64 K, and 0.340 and 0.640 Hz/point, respectively.
The parameters for the distortionless enhancement by polarization
transfer (DEPT) experiments were the same as those for 13C NMR.
The data points of the two dimensional experiments, including
correlation spectroscopy (COSY), heteronuclear multiple quantum
coherence (HMQC), and heteronuclear multiple bond connectivity
(HMBC), were set to 2 K × 256 (t2 × t1). The long-range coupling times
for HMBC were set to 40 and 70 ms. The detailed experimental
methods were the same as those previously reported.[9]
General experimental procedures
Experimental
To obtain the HR/MS data of the benzothiazepine derivatives, ultra
performance liquid chromatography (UPLC)-hybrid quadrupole-
time-of-flight mass spectrometry was carried out on a Waters Acquity
Syntheses
All of the benzothiazepine derivatives (1-27) were synthesized as
shown in Scheme 1. The typical procedure for the synthesis of
benzothiazepine 20 is described as follows. To a stirred solution
of 2′-hydroxy-4,5-dimethoxyacetophenone (I, 5 mmol, 980 mg) and
4-methoxy-1-naphthaldehyde (II, 5 mmol, 930 mg) in ethanol
(50 ml) was added an aqueous solution of KOH (50% w/v, 5 ml),
and the mixture was stirred at room temperature for 24 h. Ice-water
was added to the mixture, which was acidified with 3 N HCl to
pH = 3, to form a precipitate. The precipitate was filtered and
washed with water and methanol successively to give a chalcone
compound (III, yield: 40%, MP: 181–184 °C). 2-Aminothiophenol
(IV, 1.2 mmol, 150 mg, d: 1.17 g/ml) was added to a solution of the
chalcone (III, 1 mmol, 364 mg) in 15 ml of ethanol containing a cat-
alytic amount of gallium (III) trifluoromethanesulfonate. The reac-
tion mixture was refluxed at 85 °C for 6 h. After cooling the
reaction mixture to room temperature, a precipitate is formed.
* Correspondence to: Yoongho Lim, Division of Bioscience and Biotechnology,
Konkuk University, Hwayang-Dong 1, Kwangjin-Ku, Seoul, Korea 143-701.
E-mail: yoongho@konkuk.ac.kr
** Correspondence to: Dongsoo Koh, Department of Applied Chemistry, Dongduk
Women’s University, Seoul, Korea 136-714.
E-mail: dskoh@dongduk.ac.kr
† S Ahn and SY Shin contributed equally to this work.
a Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701,
Korea
b Department of Biological Sciences, Konkuk University, Seoul 143-701, Korea
c
Department of Applied Chemistry, Dongduk Women’s University, Seoul 136-714,
Korea
Magn. Reson. Chem. 2016, 54, 382–390
Copyright © 2015 John Wiley & Sons, Ltd.
Ahn, Seunghyun
