An Easy Access to the Synthesis of Sugar-Based N-Methyl-Pyrrolidine via [3 + 2] Cycloaddition Methodology

Article abstract of DOI:10.1002/jhet.2398

(Chemical Equation Presented) Sugar-based N-methyl-pyrrolidine derivatives have been synthesized by the cycloaddition reaction of the ylide generated from sarcosine and paraformaldehyde with the sugar-derived dipolarophile. All the newly synthesized produ

Full text of DOI:10.1002/jhet.2398

Month 2015 An Easy Access to the Synthesis of Sugar-Based N-Methyl-Pyrrolidine via
[3 + 2] Cycloaddition Methodology
Hemamalini Arasasppana and Mohan Das Thangamuthua,b
*
aDepartment of Organic Chemistry, University of Madras, Guindy Campus, Chennai, 600 025, India
bDepartment of Chemistry, School of Basic and Applied Sciences, Central University of Tamil Nadu, Thiruvarur,
610 004, India
*
E-mail: tmohandas@cutn.ac.in
Additional Supporting Information may be found in the online version of this article.
Received November 19, 2014
DOI 10.1002/jhet.2398
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Sugar-based N-methyl-pyrrolidine derivatives have been synthesized by the cycloaddition reaction of the
ylide generated from sarcosine and paraformaldehyde with the sugar-derived dipolarophile. All the newly
synthesized products were characterized by NMR (1H, 13C), mass spectroscopy and elemental analysis.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
various dipoles used, azomethine ylide is extensively used
for the construction of various biologically active com-
pounds [30,31]. Infact, Rizzi has observed the formation
of azomethine ylide by the thermal decarboxylation of
α-amino acids whose rate was accelerated in the presence
of the carbonyl compounds [32]. This had been an interest-
ing route for the synthesis of non-stabilized azomethine
ylides. Few years later, Tsuge and coworkers have shown
that the decarboxylative approach to azomethine ylide oc-
curs via the formation of an oxazolidinone intermediate
rather than the direct decarboxylation followed by carbon
dioxide elimination [33].
This report deals with the synthesis and characterization
of N-methyl-pyrrolidine derivatives obtained from 1,3-
dipolar cycloaddition reaction between sugar chalcone
and unstabilized azomethine ylide. Here, α-amino acid
decarboxylative route was chosen for the generation of
azomethine ylide from amino acid and paraformaldehyde.
To the best of our knowledge, there has been no report
on the 1,3-dipolar cycloaddition reaction of azomethine
ylide derived from paraformaldehyde and sarcosine with
sugar-chalcone dipolarophile.
In general, heterocyclic compounds have a diverse bio-
logical activity. Among the heterocyclic compounds, the
importance of pyrrolidine ring systems arises because of
its pharmacological activities [1–8], such as antimicrobial,
antitumour, anti-HIV-1, anticonvulsant, malic enzyme in-
hibitors, human melanocortin-4 receptor agonists. Pyrrol-
idine ring system is important in the construction of
various bioactive natural products [9–11]. Naturally occur-
ring alkaloid having N-methyl-pyrrolidine derivative,
Bgugaine [12], is a potent hepatotoxin in rat and human
liver cells. It also has the capability to induce significant
DNA damage in a human hepatoblastoma (HepG2) cell
line. Some direct synthetic methods have been reported
for the synthesis of pyrrolidine ring systems [13–15]. For
example, the cyclization of aminyl radicals [13], highly
stereospecific cyclization of amino allene catalyzed by an
organosamarium complex [14], 5-endo iodoamidation cy-
clization of olefinic amines [15]. Recently, it has found ap-
plication in catalysis. For the synthesis of the high-value
heterocyclic framework, in addition to the [3+ 2] cycload-
ditions [16–19] and aza Cope Mannich rearrangements
[20–23], a new catalytic approach via the modular combi-
nation of β amino aldehydes and simple olefins using an
enantioselective SOMO (singly occupied molecular orbital)
activation/cycloaddition was developed by MacMillan and
coworkers [24]. The [3 + 2] cycloaddition reaction of
azomethine ylide with alkene represents an outstanding tool
in organic synthesis to provide five-membered nitrogen het-
erocycles, generally with high regio and stereoselectivities
[25–29]. A wide variety of dipoles and dipolarophiles are
used to obtain various heterocyclic skeleton. Among the
RESULTS AND DISCUSSION
4,6-O-butylidene-D-glucopyranose, compound 1, was
synthesized from D-glucose following the literature proce-
dure [34,35]. 4,6-O-butylidene-D-glucopyranosyl-propan-
2-one, compound 2, was achieved from compound 1
through Knoevenagel condensation [36–38]. Aldol conden-
sation of compound 2 with various-substituted aromatic
aldehydes resulted in the formation of the corresponding
© 2015 HeteroCorporation

H. Arasasppan and M. D. Thangamuthu
Vol 000
α,β-unsaturated-β-C-glycosidic ketones, compounds 3–6,
in 45–68% yield. Acetylation of compounds 3–6 gave the
corresponding acetylated compounds 7–10 in 80–85%
yield. Details about the synthesis and characterization of
compounds 3–10 are discussed.
methylene groups adjacent to the N-CH3 group resonated
around 3.1 and 3.0 ppm, whereas a broad peak in the range
2.9–2.8 that correspond to the two methine protons con-
firmed the formation of the five-membered ring structure
(Fig. 2).
The 1H-NMR spectrum of compound 15 notably exhibited
a large coupling constant for the H-1 signal (δ 5.16 ppm;
3JH1,H2 9.0Hz), indicating a trans-diaxial orientation of H-1
and H-2 as expected for the β-D-configured glucopyranose
moiety. The presence of six carbons that corresponds to the
–CH2 group in the DEPT-135 experiment further confirmed
the formation of the sugar-based N-methyl-pyrrolidine
derivative, 15. The formation of the product was further
confirmed from mass and elemental analysis. The mass
spectrum of compound 15 showed a molecular ion peak
at m/z 548 [M + H]+, which confirms that the addition
takes place at the olefin double bond of the
dipolarophile to form the five-membered pyrrolidine
ring. Moreover, the product gave a satisfactory elemen-
tal analysis. Similar results were observed for the other
derivatives irrespective of the nature of substituent
present in the aromatic moiety attached to the sugar
chalcone as represented in Table 1.
Sugar-Based N-Methyl-Pyrrolidine. The ylide generated
from sarcosine, compound 11, and paraformaldehyde,
compound 12, reacts with the dipolarophile to yield
N-methyl-pyrrolidine derivatives, compounds 13–16, in
moderate to good yield (Scheme 1). The reaction
conditions were optimized using different solvents. When
the reaction was carried out in toluene, the cycloadduct was
not formed, and it maybe because of the insoluble nature of
partially protected sugar chalcone. On complete protection
of the partially protected sugar chalcone through
acetylation and by changing the solvent to a mixture of
toluene and acetonitrile, the cycloaddition reaction went
smoothly resulting in good yield. The reaction was
almost performed under neutral condition. Thus, the
reaction of α,β-unsaturated-di-O-acetyl-β-C-glycosidic
ketones, compounds 7–10, with the ylide generated using
a solvent mixture of toluene–acetonitrile in the ratio 1:1
resulted in yields of 63–78% of the corresponding sugar-
based N-methyl-pyrrolidine derivatives 13–16 (Table 1).
However, the presence of an electron-withdrawing keto
group increases the dipolarophilic reactivity of sugar
chalcone toward the azomethine ylide (Fig. 1).
CONCLUSION
Several sugar-based N-methyl-pyrrolidine derivatives
were synthesized and characterized using NMR, mass,
and elemental analysis. The formation of the five-
membered ring system was identified from NMR spectro-
scopic technique. Furthermore, the presence of β-anomeric
form of the sugar moiety was observed from the higher
coupling constant value.
The structures of the resulting N-methyl-pyrrolidine de-
1
rivatives were characterized by H-NMR and 13C-NMR
spectral techniques and also further confirmed from
1
DEPT-135 experiment. In the H-NMR spectrum of com-
pound 15, the presence of N-CH3 group that appeared as
a sharp singlet at 2.4 ppm and the presence of two
Scheme 1. Synthesis of sugar-based N-methyl-pyrrolidine derivatives, 13–16.
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An Easy Access to the Synthesis of Sugar-Based N-Methyl-Pyrrolidine via [3 + 2]
Cycloaddition Methodology
Table 1
Synthesis of sugar-based Ν-methyl-pyrrolidine derivatives, 13–16.
NMR data
Entry
1
R
Time (h)
10
Yield (%)
65
δ (Ano)/ppm 3J(H1,H2)/Hz
δ (ÀΝCΗ2)/ppm
δ (ÀCΗ)/ppm
5.17, 9.0
3.12, 2.96
2.88–2.76, 2.64–2.50b
2
8
73
5.15, 9.0
3.12, 2.99
2.85, 2.61–2.54b
l
3
4
5
5
78
63
5.16, 9.0
5.04, 9.0
3.11, 2.97
2.89–2.83
3.22, 3.09–3.03a
3.09–3.03b, 2.89–2.84
aPeaks overlapped with methine protons.
bPeaks overlapped with diastereotopic methylene protons.
EXPERIMENTAL SECTION
Chemical shifts are referenced to internal standard TMS.
Elemental analysis was performed using PerkinElmer 2400
Series II CHNS/O Analyzer (PerkinElmer, Waltham, MA,
General Methods.
D-glucose and various aldehydes
were purchased from Sigma-Aldrich Chemicals Pvt. Ltd.
(St. Louis, MO, USA) and were of high purity.
Butyraldehyde and the organic catalyst (pyrrolidine),
sarcosine and paraformaldehyde were obtained from
Sisco Research Laboratories Pvt. Ltd. (Mumbai, India).
Other reagents, such as hydrochloric acid, sodium
hydrogen carbonate, ammonium chloride, sodium acetate,
and solvents (AR Grade) were obtained from S.D. Fine-
Chem Ltd (Mumbai, India) in high purity and were used
without any further purification. Acetylacetone was
purchased from LOBA Chemie Pvt. Ltd. (Mumbai,
India). Aceticanhydride was purchased from Fischer
Chemicals Pvt. Ltd. (Mumbai, India). The solvents were
purified according to the standard methods. Column
chromatography was performed on silica gel
(100–200mesh). NMR spectra were recorded on a Bruker
DRX 300MHz instrument in either CDCl3 or DMSO-d6.
USA).
Di-Acetylated-Sugar Chalcone Derivatives
Physicochemical and Spectral Data of (E)-1-(4,6-O-Butylidene-
2,3-Diacetyl-β-D-Glucopyranosyl)-4-(4-Bromophenyl)-but-3-en-2-
one (7).
Compound 7 was obtained as a colorless
crystalline solid by the acetylation of sugar chalcone, 3
(0.44g, 1mmol) using NaOAc (0.25g, 3mmol) and Ac2O
(4ml, 40mmol).
Mp: 158–160°C; Yield: 0.45g (85%); 1H-NMR
(300 MHz, CDCl3): δ 7.55–7.39 (m, 5H, Ar–H, Alk–H),
6.70 (d, J= 15.9 Hz, 1H, Alk–H), 5.23 (t, J= 9.2Hz, 1H,
Sac–H), 4.93 (t, J =9.5 Hz, 1H, Sac–H), 4.48
(t, J =5.1 Hz, 1H, Sac–H), 4.19–4.13 (m, 2H, Sac–H),
3.41–3.39 (m, 2H, Sac–H), 2.92 (dd, J =8.7 Hz,
J = 16.4Hz, 1H, –CH2), 2.65 (dd, J =3.3 Hz, J= 16.2 Hz,
1H, –CH2), 2.06 (s, 3H, –COCH3), 2.03 (s, 3H, –COCH3),
1.59–1.56 (m, 2H, –CH2), 1.37 (q, J=7.8Hz, 2H, –CH2), 0.89
Figure 1. Mechanism for the generation of azomethine ylide by
Figure 2. General representation for the synthesis of pyrrolidine ring
decarboxylative approach.
system.
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H. Arasasppan and M. D. Thangamuthu
Vol 000
1
(t, J=7.4Hz, 3H, –CH3); 13C-NMR (75 MHz, CDCl3): δ
195.9, 170.2 (2C), 142.2, 132.3, 129.7, 126.6, 102.6, 78.4,
74.5, 73.1, 72.5, 70.8, 68.1, 43.0, 36.0, 20.8 (2C), 17.4,
13.8; Elemental analysis: Anal. Calcd. for C24H29BrO8: C,
Mp: 262–263°C; H-NMR (300 MHz, CDCl3): δ 8.74
(d, J= 15.9 Hz, 1H, Alk–H), 8.48 (d, J= 9.6Hz, 1H,
Ar–H), 8.31–8.08 (m, 8H, Ar–H), 7.02 (d, J= 15.9 Hz,
1H, Alk–H), 5.28 (t, J = 9.2 Hz, 1H, Sac–H), 5.03
(t, J =9.5 Hz, 1H, Sac–H), 4.50 (t, J =5.1 Hz, 1H,
Sac–H), 4.30–4.19 (m, 2H, Sac–H), 3.45–3.41 (m, 3H,
Sac–H), 3.08 (dd, J = 8.4 Hz, J =16.2 Hz, 1H, –CH2),
2.81 (dd, J =3.3 Hz, J = 15.9Hz, 1H, –CH2), 2.08 (s,
3H, –COCH3), 2.07 (s, 3H, –COCH3), 1.64–1.59 (m, 2H,
–CH2), 1.38 (q, J = 7.8 Hz, 2H, –CH2), 0.90 (t, J =7.4 Hz,
3H, –CH3); 13C-NMR (75 MHz, CDCl3): δ 196.0, 170.3
(2C), 140.2, 133.1, 131.3, 130.7, 130.3, 128.9, 127.9,
127.8, 127.3, 126.4, 126.2, 126.0, 125.1, 125.0, 124.6,
124.2, 122.3, 102.6, 78.5, 77.2, 74.9, 73.2, 72.6, 70.8,
68.2, 43.5, 36.0, 20.8 (2C), 17.4, 13.8; Elemental analysis:
Anal. Calcd. for C34H34O8: C, 71.56; H, 6.01%. Found: C,
71.59; H, 6.04.
54.87; H, 5.56%. Found: C, 54.92; H, 5.60.
Physicochemical and Spectral Data of (E)-1-(4,6-O-Butylidene
2,3-Diacetyl-β-D-Glucopyranosyl)-4-(4-Allyloxyphenyl)-but-3-
en-2-one (8). Compound 8 was obtained as a colorless
solid by the acetylation of sugar chalcone, 4 (0.42g,
1 mmol) using NaOAc (0.25g, 3 mmol) and Ac2O (4ml,
40mmol).
Mp: 126–128°C; Yield: 0.40 g (80%); 1H-NMR
(300 MHz, CDCl3): δ 7.50 (t, 3H, Ar–H, Alk–H),
6.93 (d, J = 8.7Hz, 2H, Ar–H), 6.61 (d, J = 16.2Hz, 1H,
Alk–H), 6.12–5.99 (m, 1H, Alk–H), 5.42 (d, J = 17.3Hz,
1H, Alk–H), 5.32 (d, J= 10.5 Hz, 1H, Alk–H), 5.23
(t, J= 9.2Hz, 1H, Sac–H), 4.94 (t, J =9.6 Hz, 1H, Sac–
H), 4.58 (d, J =5.1 Hz, 2H, –CH2), 4.48 (t, J= 5.1 Hz,
1H, Sac–H), 4.20–4.14 (m, 2H, Sac–H), 3.40–3.42 (m,
3H, Sac–H), 2.91 (dd, J = 8.4 Hz, J =16.2 Hz, 1H, –CH2),
2.63 (dd, J= 3.3 Hz, J =16.1 Hz, 1H, –CH2), 2.06 (s,
3H, –COCH3), 2.03 (s, 3H, –COCH3), 1.43–1.40 (m, 2H,
–CH2), 1.37 (q, J = 8.1 Hz, 2H, –CH2), 0.89 (t, J= 7.4 Hz,
3H, –CH3); 13C-NMR (75 MHz, CDCl3): δ 196.0, 170.3,
170.2, 160.9, 143.5, 132.7, 130.2, 127.1, 124.1, 118.1,
115.3, 102.6, 78.5, 74.8, 73.2, 72.6, 70.8, 68.9, 68.2,
42.8, 36.1, 20.8 (2C), 17.5, 13.9; Elemental analysis: Anal.
Calcd. for C27H34O9: C, 64.53; H, 6.82%. Found: C,
General Procedure for the Synthesis of Sugar-Based
N-Methyl-Pyrrolidine Derivatives (13–16).
To a solution
of ylide generated from sarcosine, 11 (1 mmol) and
paraformaldehyde, 12 (1 mmol) in 1:1 ratio of toluene and
acetonitrile, the sugar chalcone derivatives, 7–10 (1.2 mmol)
were added. After refluxing the reaction mixture for a given
period of time, it was then evaporated under reduced
pressure. The product, 13–16, was then purified by column
chromatography.
Physicochemical and Spectral Data of 4’-[4-Bromophenyl]-
3’-[2-(2,3-di-O-Acetyl-4,6-O-Butylidene-β-D-Glucopyranosyl)-
1-Oxoethyl]-1’-Methyl[Pyrrolidine] (13). Compound 13 was
obtained by the reaction of sarcosine, 11 (0.09g, 1mmol),
paraformaldehyde, 12 (0.30g, 1mmol) and sugar chalcone,
7 (0.53g, 1mmol) as a yellow syrupy liquid.
64.58; H, 6.85.
Physicochemical and Spectral Data of (E)-1-(4,6-O-Butylidene-
2,3-Diacetyl-β-D-Glucopyranosyl)-4-(3,4-Dioxanephenyl)-but-3-
en-2-one (9). Compound 9 was obtained as a yellow solid
Yield: 0.38g (65%); 1H-NMR (300MHz, CDCl3): δ
7.42 (d, J = 6.9 Hz, 2H, Ar–H), 7.16 (d, J =8.4Hz, 2H,
Ar–H), 5.17 (t, J= 9.0 Hz, 1H, Sac–H), 4.79 (t, J =9.6 Hz,
1H, Sac–H), 4.45 (t, J = 4.8 Hz, J = 5.1 Hz, 1H, Sac–H),
4.09–4.01 (q, J =10.5 Hz, 1H, –Sac–H), 3.71–3.59
(q, J =7.5 Hz, 1H, –Sac–H), 3.40–3.30 (m, 3H, Sac–H),
3.12 (q, J =8.1 Hz, 2H, –NCH2), 2.96 (q, J =7.5 Hz,
2H, –NCH2), 2.88–2.76 (m, 1H, –CH), 2.64–2.50 (m,
2H, –CH, –CH2), 2.37 (s, 3H, –NCH3), 2.31–2.29 (m,
1H, –CH2), 1.99 (s, 3H, –COCH3), 1.96 (s, 3H, –COCH3),
1.62–1.55 (m, 2H, –CH2), 1.36 (q, J= 7.8 Hz, 2H, –CH2),
0.89 (t, J = 7.4 Hz, 3H, –CH3); 13C-NMR (75 MHz,
CDCl3): δ 205.7, 170.1 (2C), 142.7, 131.8, 129.3, 120.5,
102.6, 78.3, 74.3, 72.9, 72.2, 70.7, 68.0, 64.1, 60.5, 58.3,
45.2, 43.9, 41.8, 36.0, 30.9, 20.7, 20.6, 17.4, 13.8; Elemental
analysis: Anal. Calcd. for C27H36BrNO8: C, 55.67; H, 6.23;
by the acetylation of sugar chalcone, 5 (0.41g, 1 mmol)
using NaOAc (0.25g, 3mmol) and Ac2O (4ml, 40mmol).
Mp: 114–116°C; Yield: 0.40 g (82%); 1H-NMR
(300 MHz, CDCl3): δ 7.45 (d, J = 16.2Hz, 1H, Alk–H),
7.04–7.02 (m, 2H, Ar–H), 6.83 (d, J = 8.7 Hz, 1H, Ar–H),
6.56 (d, J =15.9 Hz, 1H, Alk–H), 6.02 (s, 2H, –OCH2),
5.23 (t, J =9.3 Hz, 1H, Sac–H), 4.93 (t, J= 9.5 Hz, 1H,
Sac–H), 4.48 (t, J =5.1 Hz, 1H, Sac–H), 4.19–4.13
(m, 2H, Sac–H), 3.41–3.39 (m, 3H, Sac–H), 2.90
(dd, J =8.7Hz, J =16.1 Hz, 1H, –CH2), 2.63 (dd,
J =3.3 Hz, J= 16.1 Hz, 1H, –CH2), 2.06 (s, 3H, –COCH3),
2.03 (s, 3H, –COCH3), 1.63–1.56 (m, 2H, –CH2), 1.37
(q, J =7.5 Hz, 2H, –CH2), 0.89 (t, J = 7.4 Hz, 3H, –CH3);
13C-NMR (75 MHz, CDCl3): δ 195.9, 170.2 (2C), 150.1,
148.5, 143.4, 128.7, 125.2, 124.3, 108.7, 106.6, 102.6,
101.7, 78.5, 74.7, 73.1, 72.5, 70.7, 68.2, 42.9, 36.0, 20.8,
17.4, 13.8; Elemental analysis: Anal. Calcd. for
C25H30O10: C, 61.22; H, 6.16%. Found: C, 61.26; H, 6.19.
N, 2.40%. Found: C, 55.71; H, 6.27; N, 2.44.
Physicochemical and Spectral Data of 4’-[4-(Allyloxy)Phenyl]-
3’-[2-(2,3-di-O-Acetyl-4,6-O-Butylidene-β-D-Glucopyranosyl)-1-
Oxoethyl]-1’-Methyl[Pyrrolidine] (14). Compound 14 was
obtained by the reaction of sarcosine, 11 (0.09g, 1mmol),
paraformaldehyde, 12 (0.30g, 1mmol), and sugar
chalcone, 8 (0.50g, 1mmol) as a yellow liquid.
Physicochemical and Spectral Data of (E)-1-(4,6-O-
Butylidene-2,3-di-O-Acetyl-β-D-Glucopyranosyl)-4-(1-Pyrenyl)-
but-3-en-2-one (10). Compound 10 was obtained as a dark
yellow solid by the acetylation of the corresponding sugar
chalcone, 6.
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An Easy Access to the Synthesis of Sugar-Based N-Methyl-Pyrrolidine via [3 + 2]
Cycloaddition Methodology
Yield: 0.41 g (73%); 1H-NMR (300 MHz, CDCl3): δ
7.18 (d, J = 8.4Hz, 2H, Ar–H), 6.86 (d, J= 8.9 Hz, 2H,
Ar–H), 6.09–5.98 (m, 1H, Alk–H), 5.41 (d, J = 17.1Hz,
1H, Alk–H), 5.28 (d, J= 10.5 Hz, 1H, Alk–H), 5.15
(t, J= 9.0Hz, 1H, Sac–H), 4.78 (t, J =9.6 Hz, 1H, Sac–
H), 4.52 (t, J= 4.8 Hz, 2H, –OCH2), 4.44 (m, 2H, Sac–
H), 4.09–3.96 (m, 2H, Sac–H), 3.34–3.30 (m, 2H, Sac–
H), 3.12 (q, J = 6.6 Hz, 2H, –NCH2), 2.99 (t, J= 8.6 Hz,
2H, –NCH2), 2.85 (dd, J =2.4 Hz, J =7.4 Hz, 1H, –CH),
2.61–2.54 (m, 2H, –CH, –CH2), 2.36 (s, 3H, –NCH3),
2.34–2.33 (m, 1H, –CH2),, 2.03 (s, 3H, –COCH3), 1.96
(s, 3H, –COCH3), 1.59–1.56 (m, 2H, –CH2), 1.36 (q,
J =7.2 Hz, 2H, –CH2), 0.88 (t, J =7.4 Hz, 3H, –CH3);
13C-NMR(75 MHz, CDCl3): δ 206.2, 170.2, 170.0, 157.4,
135.7, 133.3, 128.4, 117.6, 114.9, 102.5, 78.3, 74.2,
73.0, 72.2, 70.6, 68.9, 68.0, 64.7, 60.5, 58.3, 45.6, 43.9,
42.0, 36.0, 20.7, 17.4, 13.8; Elemental analysis: Anal.
Calcd. for C30H41NO9: C, 64.38; H, 7.38; N, 2.50%.
(m, 1H, –CH), 2.63–2.50 (m, 1H, –CH2), 2.49 (s, 3H,
–NCH3), 2.36 (dd, J = 8.1 Hz, J = 16.4 Hz, 1H, –CH2),
2.02 (s, 3H, –COCH3), 1.97 (s, 3H, –COCH3), 1.57–
1.53 (m, 2H, –CH2), 1.32–1.30 (m, 2H, –CH2), 0.86
(t, J = 7.2 Hz, 3H, –CH3); 13C-NMR (75 MHz, CDCl3):
δ 206.4, 170.2, 170.1, 131.5, 130.8, 130.2, 128.8,
128.4, 128.0, 127.4, 126.4, 126.0, 125.5, 125.2, 124.9,
124.6, 122.8, 102.4, 77.0, 74.2, 72.1, 71.7, 71.3, 70.6,
67.9, 61.1, 49.4, 44.4, 42.0, 35.9, 30.7, 29.6, 20.7,
20.5, 20.2, 17.7; Elemental analysis: Anal. Calcd. for
C37H41NO8: C, 70.79; H, 6.58; N, 2.23%. Found: C,
70.82; H, 6.61; N, 2.26.
REFERENCES AND NOTES
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[3] Xun, L.; Yalin, L.; Wenfang, X. Bioorg Med Chem 2006,
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Found: C, 64.42; H, 7.43; N, 2.55.
Physicochemical and Spectral Data of 4’-[3,4-
Dioxomethylenephenyl]-3’-[2-(2,3-di-O-Acetyl-4,6-O-Butylidene-
β-D-Glucopyranosyl)-1-Oxoethyl]-1’-Methyl[Pyrrolidine] (15).
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Compound 15 was obtained by the reaction of sarcosine, 11
(0.09g, 1mmol), paraformaldehyde, 12 (0.30g, 1mmol),
and sugar chalcone, 9 (0.49g, 1mmol) as a red syrupy liquid.
Yield: 0.43 g (78%); 1H-NMR (300 MHz, CDCl3): δ
6.80 (s, 1H, Ar–H), 6.72–6.71 (m, 2H, Ar–H), 5.94
(d, J= 4.8Hz, 2H, –OCH2), 5.16 (t, J= 9.0 Hz, 1H, Sac–
H), 4.79 (t, J = 9.5 Hz, 1H, Sac–H), 4.46 (q, J= 5.1 Hz,
1H, Sac–H), 4.11–4.03 (m, 2H, Sac–H), 3.39–3.33 (m,
3H, –Sac–H), 3.11 (q, J = 7.5 Hz, 2H, –NCH2), 2.97
(t, J = 8.4Hz, 2H, –NCH2), 2.89–2.83 (m, 1H, –CH),
2.63–2.52 (m, 2H, –CH, –CH2), 2.36 (s, 3H, –NCH3),
2.33–2.29 (m, 1H, –CH2), 2.00 (s, 3H, –COCH3), 1.98
(s, 3H, –COCH3), 1.61–1.55 (m, 2H, –CH2), 1.36 (q,
J =7.5 Hz, 2H, –CH2), 0.89 (t, J =7.2 Hz, 3H, –CH3);
13C-NMR (75 MHz, CDCl3): δ 206.1, 170.2, 170.1,
147.9, 137.4, 120.5, 108.2, 102.5, 101.0, 78.4, 74.2,
72.2, 70.6, 68.0, 64.6, 60.5, 58.2, 46.1, 43.9, 41.9, 36.0,
30.9, 29.7, 20.7, 20.6, 17.4, 13.8; ESI-MS Calc. for
C28H37NO10, 547.24; m/z found, 548.25 [M+ H]+; Ele-
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H, 6.81; N, 2.56%. Found: C, 61.46; H, 6.85; N, 2.60.
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1’-Methyl[Pyrrolidine] (16). Compound 16 was obtained by
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dehyde, 12 (0.30g, 1mmol), and sugar chalcone, 10
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4.65 (q, J=9.6Hz, 1H, Sac–H), 4.36 (t, J=5.3Hz, 1H,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

H. Arasasppan and M. D. Thangamuthu
Vol 000
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