Synthesis of 6-ethyl-1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic acid

Article abstract of DOI:10.5560/ZNB.2013-3009

Interaction of 6-amino-1-ethyl-4-oxoquinoline-3-carboxylic ester (7) with chloral hydrate and hydroxylamine hydrochloride gave the corresponding isonitroso-acetamido derivative 8 which, upon treatment with concentrated sulfuric acid, was converted regioselectively into 1,2,9-trioxopyrrolo[3,2-f] quinoline-8-carboxylic acid (3). This novel tricyclic system was isolated in good yield as a stable hydrate 3H. Structural assignments of the new compounds are based on microanalytical and spectral (MS and NMR) data.

Full text of DOI:10.5560/ZNB.2013-3009

Synthesis of 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic
Acid
Randa M. Al-As’ada, Mustafa M. El-abadelaha, Salim S. Sabria, Jalal A. Zahraa, and
Wolfgang Voelterb
a
Chemistry Department, Faculty of Science, The University of Jordan, Amman 11942, Jordan
Interfakulta¨res Institut fu¨r Biochemie, Universita¨t Tu¨bingen, Hoppe-Seyler-Straße 4, 72076
b
Tu¨bingen, Germany
Reprint requests to Prof. Dr. W. Voelter. E-mail: wolfgang.voelter@uni-tuebingen.de or
Prof. Dr. M. M. El-Abadelah. E-mail: mustelab@ju.edu.jo
Z. Naturforsch. 2013, 68b, 700 – 706 / DOI: 10.5560/ZNB.2013-3009
Received January 12, 2013
Dedicated to Professor Heinrich No¨th on the occasion of his 85th birthday
Interaction of 6-amino-1-ethyl-4-oxoquinoline-3-carboxylic ester (7) with chloral hydrate and
hydroxylamine hydrochloride gave the corresponding isonitroso-acetamido derivative 8 which,
upon treatment with concentrated sulfuric acid, was converted regioselectively into 1,2,9-trioxopyr-
rolo[3,2-f]quinoline-8-carboxylic acid (3). This novel tricyclic system was isolated in good yield as
a stable hydrate 3H. Structural assignments of the new compounds are based on microanalytical and
spectral (MS and NMR) data.
Key words: 6-Amino-1-ethyl-4-oxoquinoline-3-carboxylic Ester, Isonitroso-acetamido Derivative,
Regioselective Annelation, Stable Hydrated Isatin Moiety,
1,2,9-Trioxopyrrolo[3,2-f]quinoline Derivatives
Introduction
tinib [20 – 22] or soulieotine [23, 24] (Fig. 1). Isatins
are widely employed in the synthesis of various bio-
Isatin (1H-indole-2,3-dione, Fig. 1) is an endoge- logically active compounds, such as functionalized in-
nous indole found in human blood, urine [1, 2], cere- dirubins [25] or regioisomeric isoindigos [26, 27], ex-
brospinal fluid [3, 4], and in many organisms. It is emplified by meisoindigo (Fig. 1); the latter compound
also present in plants of the genus Isatis [5], or is used in China for the treatment of chronic myelo-
Calanthe discolor LINDL. [6] or Couroupita guiane- cytic leukemia [28].
sis Aubl. [7]. Isatin is produced by an Alteromonas
On the other hand, fluoroquinolones, exemplified
sp. strain inhabiting the surface of embryos of the by ciprofloxacine [29, 30] (Fig. 2), have emerged as
caridean shrimp Palaemon macrodectylus, which pro- a major class of synthetic chemotherapeutic agents
tects them from otherwise lethal effects of infection which have a broad spectrum of activity against sev-
by the pathogenic fungus Lagenidium callinectes [8]. eral strains of bacteria [29 – 35]. Since 1986, more than
Substituted isatins are also found in plants e. g., the 25 fluoroquinolones have been approved by FDA, and
melosatin alkaloids 1a–c [9 – 11] (Fig. 1), obtained most of those remained on the market.
from the Caribbean tumorigenic plant Melochia to-
Herein, we wish to report on the synthesis of a new
mentosa, as well as the isoprenyl isatins 2a [12, 13] tricyclic system 3 (Fig. 2) incorporating a 4-pyridone
and 2b [14] (Fig. 1) from fungi. A number of recent re- moiety condensed to isatin as depicted in Scheme 1.
views have focused on the biological role of isatin and As a structural feature, the heterocyclic assembly in
the range of biological activities (e. g., anti-microbial, 3 encompasses 4-oxoquinoline (rings A, B) and isatin
anti-cancer and anti-HIV), displayed by isatin and as- (rings B, C) chemotypes. Such a new hybrid hete-
sorted isatin derivatives [15 – 18]; examples include rocyclic system might display interesting biological
methasizone [19], and the antitumor agents suni- properties.
© 2013 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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R. M. Al-As’ad et al. · 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic Acid
701
Ph
O
O
4
R1
R1
3
5
2
O
O
6
1
N
R2
N
R2
H
7
R3
H
isoprenyl isatins (2a, b)
melosatins (1a - c)
CH2
a ( R1 = H; R2
=
)
)
a (R1 = R2 = R3 = H)
b (R1 = R2 = OMe; R3 = H)
c (R2 = R3 = OMe; R1 = H)
CH2
b (R2 = H; R1
=
Me
R
Me
N
NHCSNH2
N
H
F
O
O
O
N
N
H
N
H
Me
MeO
soulieotine
methasizone
sunitinib (R = CONHCH2CH2NEt2
)
H
N
O
O
NH
O
O
N
N
H
Me
indirubin
meisoindigo
Fig. 1. Selected natural and synthetic isatin derivatives.
Results and Discussion
4-oxoquinoline 7. The preparation and satisfactory mi-
croanalysis of compounds 4 [37, 38], 5 [37, 38] and
The synthetic strategy towards the target tricyclic 6 [39, 40] were previously reported, but their MS and
system 3 commenced with the preparation of ethyl 6- NMR spectral data are lacking. Compound 7 was pre-
amino-1-ethyl-4-oxoquinoline-3-carboxylate (7), fol- pared (for use as synthon) by reduction of 6 with iron
lowed by annelating the pyrrolidine-2,3-dione moi- and ammonium chloride solution, but was not charac-
ety as outlined in Scheme 1. Thus, treatment of terized [41]. Since compound 7 served herein as key
4-nitroaniline with diethyl ethoxymethylenemalonate intermediate, it was characterized and transformed into
gave the respective enamine derivative 4 which was 3 (Scheme 1) using the classical Sandmeyer method-
then cyclized into 4-oxoquinoline-3-carboxylate 5 un- ology [42 – 46]. It follows that interaction of 7 with
der Gould–Jacobs0 reaction conditions [36]. Subse- chloral hydrate and hydroxylamine hydrochloride de-
quent N(1)-ethylation of 5 to obtain 6, followed by livered the corresponding new isonitroso-acetamido
nitro-group reduction, produced the desired 6-amino- derivative 8. Finally, this penultimate intermediate 8
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702
R. M. Al-As’ad et al. · 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic Acid
Fig. 2. A representative fluoroquinolone and an isatin-quinolone hybrid 3.
3
6
EtO2C
+
CO2Et
O2N
EtO2C
2
O2N
CO2Et
(ii)
4
(i)
2'
3'
EtOH
EtOH
1
5
OEt
NH2
N
H
4
O
4
O
4
5
8
5
8
O2N
CO2Et
O2N
CO2Et
4a
(iv)
(iii)
6
7
3
2
1
1
8a
N
N
H
Et
5
6
O
O
H
5
5
8
4
4
N
CO2Et
(vi)
H2N
CO2Et
(v)
O
1
1
N
N
N
8
OH
Et
Et
8
7
OH
O
2
O
O
2
OH
1
1
O
9
O
C
3
9b
9b
3
HN
HN
9
CO2H
CO2H
9a
9a
3a
4
3a
4
8
7
8
7
H2O
H+
B
A
6
6
5a
5a
N
N
5
5
Et
Et
3
3H
Scheme 1. (i) 130 – 140 ◦C, 2 h; (ii) (Ph)2O, 240 ◦C, 1 h; (iii) K2CO3, EtI, EtOH / reflux, 10 h; (iv) SnCl2, conc. HCl /
10 – 12 h, r. t.; (v) CCl3-CH(OH)2, NH2OH, HCl, Na2SO4, H2O / reflux, 8 h; (vi) 95% H2SO4 / 90 ◦C, 1 h.
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R. M. Al-As’ad et al. · 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic Acid
703
then underwent, in conc. H2SO4, regioselective in- and annelated indirubins for assessment of their an-
tramolecular cyclization at carbon-5 to furnish the re- tiprolifertive activities is currently under way.
spective new product 3H in 24% overall yield. Com-
pound 3H, an angular tricyclic heterocycle, is a stable
hydrate of the targeted annelated isatin 3. To the best
of our knowledge, isolable and stable monohydrated
isatins (i. e. 3,3-dihydroxyindolin-2-ones) are hitherto
undescribed in the literature. Hence, compound 3H
represents the first 4-quinolone-based tricyclic system
incorporating a stable hydrated isatin moiety (rings
B/C, Scheme 1).
Experimental Section
The following chemicals used in this study were pur-
chased from Acros and were used as received: diethyl
ethoxymethylenemalonate, p−nitroanilines, diphenyl ether,
iodoethane, chloral hydrate, hydroxylamine hydrochloride,
and anhydrous SnCl2. 1H and 13C NMR spectra were
recorded on a 500 MHz spectrometer (Bruker Avance-III).
Chemical shifts are expressed in ppm (δ units), with TMS
as internal standard; J values for H-1H coupling constants
1
The new compounds 7, 8 and 3H were character-
ized by elemental analyses, IR, MS and NMR spec-
are given in Hertz. High-resolution mass spectra (HRMS)
tral data. These data, detailed in the Experimental Sec- were acquired (in positive mode) using the electrospray ion
trap (ESI) technique by collision-induced dissociation on
a Bruker APEX-4 (7-Tesla) instrument. The samples were
dissolved in acetonitrile, diluted in spray solution (methanol-
water 1 : 1 v/v + 0.1% formic acid) and infused using a sy-
ringe pump with a flow rate of 2 µL min−1. External cal-
ibration was conducted using arginine clusters in a mass
range m/z = 175 – 871. Elemental analyses were performed
on a Euro Vector elemental analyzer, model EA 3000.
tion, are consistent with the suggested structures. Thus,
the mass spectra display the correct molecular ion
peaks for which the measured high-resolution (HRMS)
data are in good agreement with the calculated values.
DEPT and 2D (COSY, HMQC, HMBC) experiments
showed correlations that helped in the 1H and 13C sig-
nal assignments to the different carbons and their at-
tached, and/or neighboring hydrogens. For compounds
5–8, long-range correlations are observed between 5-
H and each of C-8a and C-4; likewise, 2-H is corre-
lated with each of C-8a, C-4 and CO2Et, while 8-H
is correlated with C-4a and C-6. For compound 3H,
long-range correlations are also observed between 4-H
and each of C-9b and C-5a; likewise, 5-H is correlated
with C-3a and C-9a, while 7-H is correlated with C-5a,
C-9 and CO2H. The NMR spectra of 3H reveal that
carbon-1 resonates at δ = 92.5 ppm, a value expected
for an sp3 carbon flanked by two electronegative oxy-
gen atoms, while the two hydrogens of the geminal
hydroxy groups at C-1 resonate as a broad signal at
δ = 7.35 ppm (exchangeable with D2O). Both of the
latter 1H and 13C signals constitute diagnostic criteria
in support of the existence of the keto group as a sta-
Diethyl 2-[(4-nitrophenylamino)methylene]malonate (4)
A mixture of p-nitroaniline (13.8 g, 0.1 mol) and diethyl
ethoxymethylenemalonate (21.6 g, 0.1 mol) was heated at
130–140 ◦C for 2 h, during which time the resulting EtOH
was distilled off. Thereafter, the reaction mixture was cooled
to r. t., the residual solid was collected under suction and
recrystallized from ethyl acetate to give 4. Yield: 22.8 g
(74%); m. p. 142 – 143 ◦C (lit. [37]: m. p. 142 – 143 ◦C). –
HRMS ((+)-ESI): m/z = 309.10811 (calcd. 309.10866 for
C14H17N2O6, [M + H]+), 331.09006 (calcd. 331.09061 for
C14H16NaN2O6, [M+Na]+). – 1H NMR (500 MHz, CDCl3):
δ = 1.36, 1.40 [2 t, J = 7.1 Hz, 7.1 Hz, 6H, 2 (CH3CH2)],
4.29, 4.34 (2 q, J = 7.1, 7.1 Hz, 4H, 2 (CH2Me)), 7.23 (d,
J = 9 Hz, 2H, 2-H/6-H), 8.28 (d, J = 9 Hz, 2H, 3-H/5-H),
8.51 (d, J = 13.2 Hz, 1H, 30-H), 11.20 (d, J = 13.2 Hz, 1H, N-
H/exchangeable with D2O). – 13C NMR (125 MHz, CDCl3):
δ = 14.2, 14.4 (2 CH3CH2), 60.6, 61.0 (2 OCH2Me), 97.1
(C-20), 116.4 (C-2/C-6), 126.0 (C-3/C-5), 143.9 (C-4), 144.6
(C-1), 149.7 (C-30), 165.1, 168.6 (2 CO2Et).
1
ble hydrated form. The H signal at δ = 14.81 ppm
belongs to the acidic CO2H formed by acid-catalyzed
hydrolysis of the ester group in compound 8 during its
cyclocondensation reaction.
Ethyl 6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (5)
Functionalized indirubins [25] and isoindigos [26,
27] (Fig. 1) are receiving considerable interest as
lead structures for the development of new antitu-
mor agents. Our prime interest has been related to
condensation reactions of the annelated isatin 3H
with indoxyl-3-acetates, and with the active methylene
group of (substituted) oxindoles. Based on such reac-
Compound 4 (5 g, 0.016 mol) was added to diphenyl ether
(50 mL), and the mixture was refluxed for 1 h. The so-
lution was then cooled, the resulting precipitate collected
by suction filtration, washed with cyclohexane, dried, and
recrystallized from DMF to give pure 5. Yield: 4.11 g
(98%); m. p. > 320 ◦C (lit. [38]: m. p. > 320 ◦C). –
tions of 3H, the preparation of annelated isoindigos HRMS ((+)-ESI): m/z = 263.06625 (calcd. for 263.06680
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704
R. M. Al-As’ad et al. · 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic Acid
C12H11N2O5, [M + H]+), 285.04819 (calcd. 285.04874 5.57 (s, 2H, NH2/exchangeable with D2O), 7.07 (dd,
for C12H10NaN2O5, [M+Na]+). – 1H NMR (500 MHz, J = 9.0 Hz, 2.5 Hz, 7-H), 7.40 (d, J = 2.5 Hz, 1 H, 5-H),
CF3CO2D): δ = 1.41 (t, J = 7.1 Hz, 3H, CH3CH2), 4.59 (q, 7.53 (d, J = 9.0 Hz, 1 H, 8-H), 8.50 (s, 1H, 2-H). – 13C
J = 7.1 Hz, 2H, CH2Me), 8.30 (d, J = 9.3 Hz, 1H, 8-H), 8.83 NMR (125 MHz, [D6]DMSO): δ = 15.0 (CH3CH2O), 15.2
(dd, J = 2.3 Hz, 9.3 Hz, 1H, 7-H), 9.40 (s, 1H, 2-H), 9.41 (CH3CH2N), 48.6 (NCH2Me), 60.2 (OCH2Me), 108.5 (C-5),
(d, J = 2.3 Hz, 1H, 5-H), 11.50 (s, 1H, N-H/exchangeable 108.8 (C-2), 119.2 (C-8), 121.7 (C-7), 130.7 (C-8a), 131.3
with D2O). – 13C NMR (125 MHz, CF3CO2D): δ = 14.3 (C-4a), 147.5 (C-2), 147.8 (C-6), 166.6 (CO2Et), 174.1 (C-4).
(CH3CH2O), 67.6 (OCH2Me), 108.7 (C-3), 122.4 (C-4a), – C14H16N2O3(260.29): calcd. C 64.60, H 6.20, N 10.76;
123.6 (C-8), 124.0 (C-5), 133.0 (C-7), 144.1 (C-8a), 149.6 found C 64.42, H 6.12, N 10.58.
(C-6), 150.4 (C-2), 169.3 (CO2Et), 176.9 (C-4).
Ethyl 1-ethyl-6-[2-(hydroxyimino)acetamido]-4-oxo-
Ethyl 1-ethyl-6-nitro-4-oxo-1,4-dihydroquinoline-
1,4-dihydroquinoline-8-carboxylate (8)
3-carboxylate (6)
Crystalline sodium sulfate (36 g), a hot solution of the
A stirred mixture of compound 5 (5 g, 0.019 mol), amino ester 7 (3.5 g, 0.013 mol) in 4% aqueous hydrochloric
K2CO3 (8 g, 0.058 mol), iodoethane (24.96 g, 0.162 mol), acid (2 mL), and a solution of hydroxylamine hydrochloride
and EtOH (20 mL) was refluxed for 10 h. The reac- (5.5 g, 0.079 mol) in water (12 mL) were added successively
tion mixture was then evaporated to dryness and ex- to a solution of chloral hydrate (4.5 g, 0.03 mol) in water
tracted with CH2Cl2(2 × 20 mL). The combined CH2Cl2 (23 mL). Thereafter, the reaction mixture was refluxed
extracts were washed with H2O, dried, and evaporated with continuous stirring for 8 h, and the resulting solu-
to dryness. The residual solid was recrystallized from tion was filtered while hot. The precipitated product was
EtOH to yield 6. Yield: 4.3 g (83%); m. p. 229 – 231 ◦C collected by suction filtration, washed with hot water and
(decomp.) (lit. [39]: m. p. 230 – 232 ◦C (decomp.)). – dried to give 8. Yield: 3.5 g (82%); m. p. 219 – 220 ◦C. –
HRMS ((+)-ESI): m/z = 291.09755 (calcd. 291.09810 for HRMS ((+)-ESI): m/z = 332.12410 (calcd. 332.12465 for
C14H15N2O5, [M + H]+), 313.07949 (calcd. 313.08004 C16H18N3O5, [M + H]+), 354.10604 (calcd. 354.10659
for C14H14NaN2O5, [M+Na]+). – 1H NMR (500 MHz, for C16H17NaN3O5, [M+Na]+). – 1H NMR (500 MHz,
[D6]DMSO): δ = 1.30 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.40 [D6]DMSO): δ = 1.29 (t, J = 7.1 Hz, 3H, CH3CH2O),
(t, J = 7.0 Hz, 3H, NCH2CH3), 4.26 (q, J = 7.1 Hz, 2H, 1.40 (t, J = 7.0 Hz, 3H, CH3CH2N), 4.23 (q, J = 7.1 Hz,
OCH2Me), 4.46 (q, J = 7.0 Hz, 2H, NCH2Me), 8.1 (d, OCH2Me), 4.40 (q, J = 7.0 Hz, NCH2Me), 7.70 (s, 1H,
J = 9.0 Hz, 1H, 8-H), 8.50 (dd, J = 9.0 Hz, 2.8 Hz, 1H, 7- CH=NOH), 7.83 (d, J = 9.1 Hz, 1 H, 8-H), 8.13 (dd,
H), 8.78 (s, 1H, 2-H), 8.90 (d, J = 2.8 Hz, 1H, 5-H). – 13C J = 9.1 Hz, 2.1 Hz, 7-H), 8.58 (d, J = 2.1 Hz, 1H, 5-H), 8.66,
NMR (125 MHz, [D6]DMSO): δ = 14.6 (OCH2CH3), 14.7 (s, 1H, 2-H), 10.55 (s, 1H, N-H/exchangeable with D2O),
(NCH2CH3), 49.0 (NCH2Me), 60.6 (OCH2Me), 112.2 (C-3), 12.26 (d, 1H, CH=NO-H/exchangeable with D2O). – 13C
119.8 (C-8), 122.8 (C-5), 127.1 (C-7), 128.4 (C-6), 143.0 (C- NMR (125 MHz, [D6]DMSO): δ = 14.9 (OCH2CH3), 15.0
8a), 144.1 (C-4a), 150.8 (C-2), 164.4 (CO2Et), 172.5 (C-4).
(CH3CH2N), 48.7 (NCH2Me), 60.5 (OCH2Me), 110.5 (C-3),
117.3 (C-5), 119.1 (C-8), 126.2 (C-7), 130.1 (C-6), 136.1
(C-8a), 136.9 (C-4a), 145.2 (CH=NOH), 149.6 (C-2), 161.9
(O=C−NH), 166.2 (CO2Et), 174.0 (C-4). – C16H17N3O5
(331.32): calcd. C 58.00, H 5.17, N 12.68; found C 57.84, H
5.26, N 12.50.
Ethyl 6-amino-1-ethyl-4-oxo-1,4-dihydroquinoline-
3-carboxylate (7)
Anhydrous stannous chloride (2.5 g, 14 mmol) was added
portion-wise to a stirred solution of the nitro compound 6
(1.0 g, 3.4 mmol) in conc. HCl (20 mL), cooled at 2 – 5 ◦C.
The reaction mixture was stirred for one additional hour at
2 – 5 ◦C and for 20 h at r. t. Thereafter, the solution was diluted
with water (200 mL) and treated portion-wise with a 40%
6-Ethyl-1,1-dihydroxy-2,9-dioxo-2,3,6,9-tetrahydro-
1H-pyrrolo[3,2-f]quinoline-8-carboxylic acid (3H)
Compound 8 (0.6 g; 1.8 mmol) was added portion-
aqueous sodium hydroxide solution to pH ∼11. The resulting wise to 95% sulfuric acid (4 mL) preheated at 65 – 70 ◦C
faint-yellowish precipitate was collected by suction filtration, under stirring. Thereafter, the temperature of the reac-
washed with water, and dried to give 7. Yield: 0.68 g (77%); tion mixture was raised to 90 ◦C and maintained there for
m. p. 209 – 211 ◦C. – HRMS ((+)-ESI): m/z = 261.12337 1 h. The resulting solution was then cooled to r. t., treated
(calcd. 261.12392 for C14H17N2O3, [M + H]+), 283.10531 with crushed ice (200 g), and allowed to stand overnight.
(calcd. 283.10586 for C14H16NaN2O3, [M+Na]+). – 1H The precipitated product was filtered, washed succes-
NMR (500 MHz, [D6]DMSO): δ = 1.27 (t, J = 7.1 Hz, sively with hot water and cold methanol (10 mL), and
3H, CH3CH2O), 1.35 (t, J = 7.0 Hz, 3H, CH3CH2N), 4.20 dried to give 3H. Yield: 0.35 g (64%); m. p. > 350 ◦C. –
(q, J = 7.1 Hz, OCH2Me), 4.32 (q, J = 7.0 Hz, NCH2Me), HRMS ((+)-ESI): m/z = 305.07718 (calcd. 305.07736 for
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R. M. Al-As’ad et al. · 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic Acid
705
C14H13N2O6, [M + H]+), 327.05912 (calcd. 327.05931 (C-1), 108.3 (C-8), 118.4 (C-4), 121.1 (C-5), 123.8 (C-9a),
for C14H12NaN2O6, [M+Na]+). – 1H NMR (500 MHz, 127.6 (C-9b), 135.4 (C-5a), 140.8 (C-3a), 148.8 (C-7), 166.0
[D6]DMSO): δ = 1.43 (t, J = 7.1 Hz, 3H, CH2CH3), 4.65 (CO2H), 174.4 (C-2), 177.9 (C-9). – C14H12N2O6 (304.25):
(q, J = 7.1 Hz, 2H, CH2Me), 7.35 (s, 2H, (HO)2C-1/ calcd. C 55.27, H 3.98, N 9.21; found C 55.03, H 3.86, N
exchangeable with D2O), 7.52 (d, J = 9 Hz, 1H, 4-H), 9.08.
8.08 (d, J = 9 Hz, 1H, 5-H), 9.01 (s, 1H, 7-H), 10.70
Acknowledgement
(s, 1H, N-H/exchangeable with D2O), 14.51 (s, 1H,
CO2H/exchangeable with D2O). – 13C NMR (125 MHz,
This research work has been supported financially by the
[D6]DMSO): δ = 15.1 (CH2CH3), 50.3 (CH2Me), 92.5
Scientific Research Support Fund (SRSF) at Amman, Jordan.
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