Design, Synthesis, and Antibacterial Evaluation of Propylene-tethered 8-Methoxyl Ciprofloxacin-isatin Hybrids

Article abstract of DOI:10.1002/jhet.3279

A series of 8-methoxyl ciprofloxacin (8-OMe CPFX)-isatin hybrids 3a–f and 4a–f tethered through propylene were designed, synthesized, and examined for their in vitro antibacterial activities against a panel of Gram-positive and Gram-negative pathogens including drug-resistant bacteria. All the synthesized hybrids (minimum inhibitory concentration: ≤0.03–64?μg/mL) exhibited considerable activities against the tested strains, especially against the Gram-negative pathogens. Among them, hybrid 3b was no inferior to the parent 8-OMe CPFX that could act as a starting point for further optimization.

Full text of DOI:10.1002/jhet.3279

Month 2018
Design, Synthesis, and Antibacterial Evaluation of Propylene-tethered
8-Methoxyl Ciprofloxacin-isatin Hybrids
*
Hua Guo
School of Chemistry and Life Science, Anshan Normal University, Anshan 114007, Liaoning, China
*E-mail: m13704127672@163.com
Received May 7, 2018
DOI 10.1002/jhet.3279
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A series of 8-methoxyl ciprofloxacin (8-OMe CPFX)-isatin hybrids 3a–f and 4a–f tethered through pro-
pylene were designed, synthesized, and examined for their in vitro antibacterial activities against a panel of
Gram-positive and Gram-negative pathogens including drug-resistant bacteria. All the synthesized hybrids
(minimum inhibitory concentration: ≤0.03–64 μg/mL) exhibited considerable activities against the tested
strains, especially against the Gram-negative pathogens. Among them, hybrid 3b was no inferior to the par-
ent 8-OMe CPFX that could act as a starting point for further optimization.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
the quinolone moiety could enhancement of the activity
against Gram-positive organisms and anaerobes while
maintaining excellent potency against Gram-negative
bacteria [18]. It is worth to notice that some of the
8-methoxyl ciprofloxacin (8-OMe CPFX, Fig. 1)
derivatives exhibit considerable antibacterial activity
[19,20]. Obviously, 8-OMe CPFX is a reasonable choice
used to develop new antibacterial agents.
Isatin is an endogenous compound identified in many
organisms and has the ability to exert several noncovalent
interactions such as Van der Waals force and hydrogen
bonds [21,22]. Isatin derivatives endow with a variety of
biological properties including antibacterial activity, and
some isatin-based compounds have been approved for
clinical use [23,24]. Thus, isatin is a useful chemical
protype to exploit new drugs.
Based on the aforementioned research results and as an
ongoing program to develop novel antibacterial agents, a
series of 8-OMe CPFX-isatin hybrids 3a–f and 4a–f
tethered through propylene were designed, synthesized,
and examined for their in vitro antibacterial activities
against clinically important Gram-positive and Gram-
negative pathogens including drug-resistant bacteria. The
design strategy is illustrated in Figure 2.
Gram-positive and Gram-negative bacteria, which are
the most common pathogens in hospital and community
settings, are capable of causing various serious and even
fatal infections [1,2]. Antibiotics are the key weapons in
the fight against bacterial infection, but the overuse and
misuse of antibiotics have triggered increased drug
resistance [3]. Currently, antimicrobial resistance
constitutes a global health problem. To combat antibiotic
resistance, the paucity of new antibacterial drugs is
evident [4].
The current arsenal of broad spectrum antibiotics is
dominated by only four major scaffolds: cephalosporins,
penicillins, macrolides, and quinolones [5,6]. Among
them, quinolones as the second largest antibiotics are
used widely in the treatment of various bacterial
infections caused by both Gram-positive and Gram-
negative pathogens [7–9]. Moreover, besides typical
antibacterial activity, quinolone motif as a multivalent
scaffold exhibited diverse biological properties [10] such
as antitubercular [11], antimalarial [12,13], and anticancer
[14] activities, which play a pivotal role in drug
development. Unfortunately, like other antibiotics,
bacteria have already developed resistance to quinolone
antibiotics, making them more and more ineffective
[15–17]. Thus, it is of paramount importance to develop
new quinolone antibiotics to overcome drug resistance.
The structure–activity relationship indicated that the
introduction of the methoxyl group on the C-8 position of
RESULTS AND DISCUSSION
The synthetic pathway for the desired hybrids 3a–f and
4a–f is described in Scheme 1. C-5 substituted isatins 1a,b
© 2018 Wiley Periodicals, Inc.

H. Guo
Vol 000
Similar as their anti-Gram-positive bacteria activity,
mono-isatin hybrids were more active than the
corresponding bis-isatin hybrids against Gram-negative
pathogens, which may attribute to the fact that carboxylic
acid on quinolone motif is essential for gyrase binding
and bacterial membrane transport. In particular, the most
active hybrid 3b was comparable to or better than the
parent 8-OMe CPFX and was far more potent than VAN
against Gram-negative organisms, which could act as a
lead for further optimization.
Figure 1. Chemical structure of 8-OMe CPFX.
were alkylated with 1,3-dibromopropane to afford N-(3-
bromopropyl) isatins 2a,b, which were then incorporated
into 8-OMe CPFX moiety to give the desired targets 3a,b
and 4a,b. Subsequently, condensation of hybrids 3a,b or
4a,b with the corresponding alkoxyamine yielded other
conjugates 3c–f and 4c–f [25].
All 8-OMe CPFX-isatin hybrids 3a–f and 4a–f were
evaluated for their in vitro antibacterial activities against
a panel of Gram-positive and Gram-negative pathogens
[26]. The minimum inhibitory concentration (MIC) is
defined as the minimum concentration of compound
required to give 90% inhibition of bacterial growth. The
results were listed in Tables 1 and 2, respectively.
EXPERIMENTAL SECTION
Synthesis. General procedure for the preparation of 3a,b
and 4a,b. N-(3-bromopropyl) isatins 2a,b were prepared
by literature reported method [25]. A mixture of N-(3-
bromopropyl) isatins 2a,b (1.4 mmol), 8-OMe CPFX
(1 mmol) and K2CO3 (3 mmol) in DMF (10 mL) was
stirred at room temperature for 5 days. After filtration, the
filtrate was concentrated under reduced pressure. The
residue was purified by MPLC to provide the desired
targets 3a,b and 4a,b.
From Table 1, it can be concluded that all 8-OMe CPFX
hybrids 3a–f bearing mono-isatin motif exhibited
considerable antibacterial activities against all of the
tested Gram-positive strains with MIC in a range of 0.25
to 64 μg/mL, but less active than the parent 8-OMe
CPFX and CPFX. The structure–activity relationship
indicated that introduction of imine at C-3 position of
isatin moiety seems did not increase the activity greatly;
mono-isatin hybrids were far more potent than the
corresponding bis-isatin hybrids.
As it can be seen from Table 2, all 8-OMe CPFX hybrids
3a–f exhibited promising antibacterial activities against all
of the tested Gram-negative strains with MIC ranging from
≤0.03 to 8 μg/mL. Further analysis revealed that the MICs
of hybrids 3a–f were < 1 μg/mL against the majority of the
tested pathogens. In general, introduction of imine at C-3
position of isatin moiety was detrimental to the activity.
1-Cyclopropyl-7-(4-(3-(2,3-dioxoindolin-1-yl)propyl)pip-
erazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinol-
ine-3-carboxylic acid (3a).
Brown solid, yield: 11%. 1H
NMR (400 MHz, DMSO-d6) δ 1.14–1.28 (4H, m,
2 × cyclopropyl-CH2), 2.02 (2H, t, –CH2–), 2.96 (4H, s,
piperazine-4H), 3.18 (4H, s, piperazine-4H), 3.84 (2H, t,
–CH2–), 3.87 (3H, s, OCH3), 3.98–4.00 (1H, m,
cyclopropyl-CH), 4.27 (2H, t, –CH2–), 7.06–8.42 (6H, m,
Ar-H). ESI-MS m/z: 549 [M + H]+. Elemental Anal.
Calcd (%) for C29H29FN4O6: C, 63.50; H, 5.33; N,
10.21; Found: C, 63.27; H, 5.14; N, 10.03.
11-Cyclopropyl-6-fluoro-8-methoxy-7-(4-(3-(5-methyl-2,3-
dioxoindolin-1-yl)propyl)piperazin-1-yl)-4-oxo-1,4-dihyd-
roquinoline-3-carboxylic acid (3b).
Brown solid, yield:
26%. 1H NMR (400 MHz, DMSO-d6) δ 1.12–1.26 (4H, m,
Figure 2. The design strategy of 8-OMe CPFX-isatin hybrids. [Color figure can be viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Design, Synthesis, and Antibacterial Evaluation of Propylene-tethered 8-methoxyl
Ciprofloxacin-isatin Hybrids
Scheme 1. Synthetic route of hybrids 3a-f and 4a-f.
Table 1
In vitro antibacterial activity of hybrids 3a–f and 4a–f against Gram-positive strains.
MIC (μg/mL)
Compd.
MSSE
0.5
0.5
0.25
0.5
0.5
2
MRSE
MSSA
MRSA
E.fa.
E.fm.
3a
3b
3c
3d
3e
3f
4
8
8
8
4
1
1
2
4
4
1
1
2
1
2
4
4
2
2
4
16
8
64
16
16
8
4
2
2
16
4a
4b
4c
4d
4e
4f
64
>128
>128
>128
>128
>128
>128
4
64
32
>128
128
128
>128
32
128
>128
>128
>128
128
>128
>128
>128
>128
>128
>128
>128
8
64
32
16
64
64
0.125
0.125
1
>128
>128
>128
>128
>128
0.25
0.25
1
CPFX
8-OMeCPFX
VAN
0.25
0.125
0.5
0.5
1
4
2
1
8
1
Abbreviations: MSSE, methicillin-sensitive Staphylococcus epidermidis; MRSE, methicillin-resistant Staphylococcus epidermidis; MSSA, methicillin-
sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; E.fa., Enterococcus faecalis ATCC; E.fm., Enterococcus faecium;
CPFX, ciprofloxacin; 8-OMe CPFX, 8-methoxy ciprofloxacin; VAN, vancomycin.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

H. Guo
Vol 000
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Design, Synthesis, and Antibacterial Evaluation of Propylene-tethered 8-methoxyl
Ciprofloxacin-isatin Hybrids
2 × cyclopropyl-CH2), 2.01 (2H, t, –CH2–), 2.22 (3H,
s, CH3), 2.98 (4H, s, piperazine-4H), 3.21 (4H, s,
piperazine-4H), 3.84 (2H, t, –CH2–), 3.87 (3H, s,
OCH3), 3.99–4.00 (1H, m, cyclopropyl-CH), 4.24 (2H,
t, –CH2–), 7.08–8.44 (5H, m, Ar-H). ESI-MS m/z:
cyclopropyl-CH), 4.16–4.22 (5H, m, –CH2– and
NOCH3), 7.04–8.42 (6H, m, Ar-H). ESI-MS m/z: 578
[M + H]+. Elemental Anal. Calcd (%) for C30H32FN5O6:
C, 62.38; H, 5.58; N, 12.12; Found: C, 62.22; H, 5.37;
N, 12.03.
563 [M
+
H]+. Elemental Anal. Calcd (%) for
1-Cyclopropyl-6-fluoro-8-methoxy-7-(4-(3-(3-(methoxyi-
mino)-5-methyl-2-oxoindolin-1-yl)propyl)piperazin-1-yl)-
4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3d).
Yellow solid, yield: 67%. 1H NMR (400 MHz,
DMSO-d6) δ 1.10–1.28 (4H, m, 2 × cyclopropyl-CH2),
2.00 (2H, t, –CH2–), 2.23 (3H, s, CH3), 3.04 (4H, s,
piperazine-4H), 3.32 (4H, s, piperazine-4H), 3.82–3.90
(5H, m, –CH2– and OCH3), 3.99–4.01 (1H, m,
cyclopropyl-CH), 4.15–4.21 (5H, m, –CH2– and
NOCH3), 7.10–8.41 (5H, m, Ar-H). ESI-MS m/z: 592
[M + H]+. Elemental Anal. Calcd (%) for C31H34FN5O6:
C, 62.93; H, 5.79; N, 11.84; Found: C, 62.77; H, 5.57;
N, 11.68.
C30H31FN4O6: C, 64.05; H, 5.55; N, 9.96; Found: C,
63.88; H, 5.34; N, 9.72.
3-(2,3-Dioxoindolin-1-yl) propyl 1-cyclopropyl-7-(4-(3-
(2,3-dioxoindolin-1-yl)propyl)piperazin-1-yl)-6-fluoro-8-
methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
1
(4a).
Brown solid, yield: 17%. H NMR (400 MHz,
DMSO-d6) δ 1.10–1.28 (4H, m, 2 × cyclopropyl-CH2),
1.85 (2H, t, –CH2–), 2.04 (2H, t, –CH2–), 2.48 (2H, t,
–CH2–), 3.01 (4H, s, piperazine-4H), 3.32 (4H, s,
piperazine-4H), 3.74–3.90 (7H, m, 2 × –CH2– and
OCH3), 3.99–4.01 (1H, m, cyclopropyl-CH), 4.24 (2H, t,
–CH2–), 7.05–8.46 (10H, m, Ar-H). ESI-MS m/z: 736
[M + H]+. Elemental Anal. Calcd (%) for C40H38FN5O8:
C, 65.30; H, 5.21; N, 9.52; Found: C, 65.09; H, 5.04; N,
9.37.
1-Cyclopropyl-7-(4-(3-(3-(ethoxyimino)-2-oxoindolin-1-yl)
propyl)piperazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (3e).
Yellow solid,
1
3-(5-Methyl-2,3-dioxoindolin-1-yl) propyl 1-cyclopropyl-
6-fluoro-8-methoxy-7-(4-(3-(5-methyl-2,3-dioxoindolin-1-
yield: 46%. H NMR (400 MHz, DMSO-d6) δ 1.10–1.28
(4H, m, 2 × cyclopropyl-CH2), 1.36 (3H, t, NOCH2CH3),
2.03 (2H, t, –CH2–), 2.96 (4H, s, piperazine-4H), 3.22
(4H, s, piperazine-4H), 3.85–3.92 (5H, m, –CH2– and
OCH3), 3.98–3.99 (1H, m, cyclopropyl-CH), 4.20 (2H, t,
–CH2–), 4.37 (2H, q, NOCH2CH3), 7.06–8.46 (6H, s, Ar-
H). ESI-MS m/z: 592 [M + H]+. Elemental Anal. Calcd
(%) for C31H34FN5O6: C, 62.93; H, 5.79; N, 11.84;
Found: C, 62.69; H, 5.51; N, 11.59.
yl)propyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-
1
carboxylate (4b).
Brown solid, yield: 14%. H NMR
(400 MHz, DMSO-d6)
δ
1.20–1.37 (4H, m,
2 × cyclopropyl-CH2), 2.02 (2H, t, –CH2–), 2.20 (2H, t,
–CH2–), 2.24 (3H, s, CH3), 2.28 (3H, s, CH3), 2.54 (2H,
t, –CH2–), 2.82 (4H, s, piperazine-4H), 3.30 (4H, s,
piperazine-4H), 3.74–3.89 (5H, m, –CH2– and OCH3),
3.98–4.03 (3H, m, –CH2– and cyclopropyl-CH), 4.36
(2H, t, –CH2–), 7.01–8.47 (8H, m, Ar-H). ESI-MS m/z:
3-(2,3-Dioxoindolin-1-yl) propyl 1-cyclopropyl-7-(4-(3-
(2,3-dioxoindolin-1-yl)propyl)piperazin-1-yl)-6-fluoro-8-
764 [M
+
H]+. Elemental Anal. Calcd (%) for
methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
C42H42FN5O8: C, 66.04; H, 5.54; N, 9.17; Found: C,
65.79; H, 5.28; N, 9.02.
1
(3f).
Yellow solid, yield: 39%. H NMR (400 MHz,
DMSO-d6) δ 1.09–1.26 (4H, m, 2 × cyclopropyl-CH2),
1.36 (3H, t, NOCH2CH3), 2.00 (2H, t, –CH2–), 2.24 (3H,
s, CH3), 3.00 (4H, s, piperazine-4H), 3.34 (4H, s,
piperazine-4H), 3.86–3.92 (5H, m, –CH2– and OCH3),
3.99–4.02 (1H, m, cyclopropyl-CH), 4.16 (2H, t, –CH2–),
4.36 (2H, q, NOCH2CH3), 7.08–8.48 (5H, m, Ar-H).
ESI-MS m/z: 606 [M + H]+. Elemental Anal. Calcd (%)
for C32H36FN5O6: C, 63.46; H, 5.99; N, 11.56; Found:
C, 63.18; H, 5.79; N, 11.38.
The general procedure for preparing targets 3c–f and
4c–f.
A mixture of methoxylamine or ethoxylamine
hydrochloride (8 mmol), sodium bicarbonate (15 mmol),
and 3a,b or 4a,b (5 mmol) in a mixture of water (10 mL)
and methanol (10 mL) was stirred at room temperature
for 24 h. After removal of the solvent, the residue was
diluted with water (10 mL) and filtered. The solid crude
product was purified by silica gel chromatography eluted
with DCM to v (DCM):v (MeOH) = 10:1 to give the title
hybrids 3c–f and 4c–f.
3-(3-(Methoxyimino)-2-oxoindolin-1-yl) propyl 1-cyclopro
pyl-6-fluoro-8-methoxy-7-(4-(3-(3-(methoxyimino)-2-oxo-
indolin-1-yl)propyl)piperazin-1-yl)-4-oxo-1,4-dihydroqui-
1-Cyclopropyl-6-fluoro-8-methoxy-7-(4-(3-(3-(methoxyim-
ino)-2-oxoindolin-1-yl)propyl)piperazin-1-yl)-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (3c).
Yellow solid,
noline-3-carboxylate (4c).
Yellow solid, yield: 74%. 1H
1
yield: 53%. H NMR (400 MHz, DMSO-d6) δ 1.12–1.26
(4H, m, 2 × cyclopropyl-CH2), 2.02 (2H, t, –CH2–), 2.88
(4H, s, piperazine-4H), 3.22 (4H, s, piperazine-4H), 3.86
(3H, s, OCH3), 3.90 (2H, t, –CH2–), 3.99–4.00 (1H, m,
NMR (400 MHz, DMSO-d6) δ 1.12–1.26 (4H, m,
2 × cyclopropyl-CH2), 1.85 (2H, t, –CH2–), 2.02 (2H, t,
–CH2–), 2.56 (2H, t, –CH2–), 2.98 (4H, s, piperazine-
4H), 3.28 (4H, s, piperazine-4H), 3.72–3.88 (7H, m,
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2 × –CH2– and OCH3), 3.99–4.01 (1H, m, cyclopropyl-
CH), 4.14–4.21 (8H, m, –CH2– and 2 × NOCH3),
7.07–8.43 (10H, m, Ar-H). ESI-MS m/z: 794 [M + H]+.
Elemental Anal. Calcd (%) for C42H44FN7O8: C, 63.55;
H, 5.59; N, 12.35; Found: C, 63.29; H, 5.37; N, 12.16.
Antibacterial MIC determination.
All hybrids were
screened for their in vitro antibacterial activity against
representative Gram-positive and Gram-negative strains,
by means of standard twofold serial dilution method
using agar media. Hybrids (10.0 mg) were dissolved in
0.1 N NaOH solution and water (10 mL). Further
progressive twofolds serial dilution with melted Mueller–
Hinton agar was performed to obtain the required
concentrations of 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25,
0.125, 0.06, and 0.03 μg/mL. Petri dishes were incubated
with 104 colony-forming units and incubated at 35°C for
18–24 h.
3-(3-(Methoxyimino)-5-methyl-2-oxoindolin-1-yl) propyl
1-cyclopropyl-6-fluoro-8-methoxy-7-(4-(3-(3-(methoxyimi-
no)-5-methyl-2-oxoindolin-1-yl)propyl)piperazin-1-yl)-4-
oxo-1,4-dihydroquinoline-3-carboxylate (4d).
Yellow
solid, yield: 45%. 1H NMR (400 MHz, DMSO-d6) δ
1.10–1.26 (4H, m, 2 × cyclopropyl-CH2), 1.86 (2H, t,
–CH2–), 2.02 (2H, t, –CH2–), 2.23 (3H, s, CH3), 2.27
(3H, s, CH3), 2.44 (2H, t, –CH2–), 2.69 (4H, s,
piperazine-4H), 3.12 (4H, s, piperazine-4H), 3.74–3.89
(7H, m, 2 × –CH2– and OCH3), 4.00–4.02 (1H, m,
cyclopropyl-CH), 4.12–4.20 (8H, m, –CH2– and
2 × NOCH3), 7.05–8.46 (8H, m, Ar-H). ESI-MS m/z:
CONCLUSION
In conclusion, a series of 8-OMe CPFX-isatin hybrids
were designed, synthesized, and evaluated for their
in vitro antibacterial activity against a panel of clinically
important pathogens. The results showed that the hybrids
822 [M
+
H]+. Elemental Anal. Calcd (%) for
C44H48FN7O8: C, 64.30; H, 5.89; N, 11.93; Found: C,
64.06; H, 5.77; N, 11.81.
bearing
mono-isatin
motif
displayed
excellent
antibacterial activity especially against Gram-negative
bacteria. Among them, hybrid 3b was no inferior to the
parent 8-OMe CPFX against the majority of the tested
pathogens, worth to be further studied.
3-(3-(Ethoxyimino)-2-oxoindolin-1-yl) propyl 1-cycloprop
yl-7-(4-(3-(3-(ethoxyimino)-2-oxoindolin-1-yl)propyl)
piperazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroqui-
noline-3-carboxylate (4e).
Yellow solid, yield: 36%. 1H
NMR (400 MHz, DMSO-d6) δ 1.10–1.26 (4H, m,
2 × cyclopropyl-CH2), 1.36 (6H, t, 2 × NOCH2CH3),
1.86 (2H, t, –CH2–), 2.02 (2H, t, –CH2–), 2.48 (2H, t,
–CH2–), 2.78 (4H, s, piperazine-4H), 3.16 (4H, s,
piperazine-4H), 3.72–3.88 (7H, m, 2 × –CH2– and
OCH3), 3.98–4.00 (1H, m, cyclopropyl-CH), 4.16 (2H, t,
–CH2–), 4.42 (4H, q, 2 × NOCH2CH3), 7.06–8.41 (10H,
m, Ar-H). ESI-MS m/z: 822 [M + H]+. Elemental Anal.
Calcd (%) for C44H48FN7O8: C, 64.30; H, 5.89; N,
11.93; Found: C, 64.17; H, 5.69; N, 11.73.
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3-(3-(Ethoxyimino)-5-methyl-2-oxoindolin-1-yl)
propyl
1-cyclopropyl-7-(4-(3-(3-(ethoxyimino)-5-methyl-2-oxoin-
dolin-1-yl)propyl)piperazin-1-yl)-6-fluoro-8-methoxy-4-
oxo-1,4-dihydroquinoline-3-carboxylate (4f).
Yellow
solid, yield: 46%. 1H NMR (400 MHz, DMSO-d6) δ
1.10–1.28 (4H, m, 2 × cyclopropyl-CH2), 1.35 (6H, t,
2 × NOCH2CH3), 1.74 (2H, t, –CH2–), 2.02 (2H, t,
–CH2–), 2.24 (3H, s, CH3), 2.26 (3H, s, CH3), 2.40
(2H, t, –CH2–), 2.80 (4H, s, piperazine-4H), 3.24 (4H,
s, piperazine-4H), 3.74–3.90 (7H, m, 2 × –CH2– and
OCH3), 3.99–4.01 (1H, m, cyclopropyl-CH), 4.18 (2H,
t, –CH2–), 4.44 (4H, q, 2 × NOCH2CH3), 7.07–8.44
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(8H, m, Ar-H). ESI-MS m/z: 850 [M
+
H]+.
Elemental Anal. Calcd (%) for C46H54FN7O8: C,
65.00; H, 6.17; N, 11.54; Found: C, 64.83; H, 6.01;
N, 11.32.
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DOI 10.1002/jhet