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anionic site of BChE, consisting of Val and Leu residues, allows fac-
ile insertion of 8e into the active site gorge13 (Fig. 4). This com-
pound shows more favorable interactions with choline binding
site instead of the peripheral anionic site residues in contrast to
AChE receptor.
In conclusion, a series of piperidone-grafted spiropyrrolizines
has been synthesized by the three-component [3+2]-cycloaddition
reaction of azomethine ylides to highly functionalized dipolaro-
philes. Most of the synthesized compounds were found to be sig-
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nificantly active with IC50 values ranging from 3.13 to 22.32
Compounds, 8g and 8e, showed the maximum inhibitory activity
against AChE and BChE with IC50 values of 3.36 and 3.13 M,
respectively. The presence of two C@C functionalities in these spi-
roheterocyclic hybrids render them valuable synthons for the con-
struction of complex heterocycles of biological importance and this
work is currently under progress in our laboratory.
lM.
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Acknowledgments
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The authors thank the Malaysian Government and Universiti
Sains Malaysia for RUT Grant [1001/PKIMIA/855006] and RU Grant
[1001/PKIMIA/811221], to conduct this research. Y.K. thanks Uni-
versity Sains Malaysia for financial support by way of a fellowship.
29. Basiri, A.; Murugaiyah, V.; Osman, H.; Hemamalini, M.; Fun, H. K. Acta Cryst.
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30. Synthesis of 100-carbonyl-(spiro[2.30]5-chloro oxindole-hexahydro-1H-pyrrolizine)-
300,500-bis[(E)-arylmethylidene]tetrahydro-400(1H)-pyridinones (8a–k): A mixture
of 1-acryloyl-3,5-diarylidenepiperidin-4-ones (5, 0.364 mmol), 5-chloroisatin
Supplementary data
(6, 0.364 mmol) and L-proline (7, 0.364 mmol) was dissolved in methanol
(5 mL) and heated under reflux for 5 h. The reaction progress was monitored by
TLC analysis. After completion of the reaction, the precipitate obtained was
filtered and washed with cold methanol (25 mL) to afford the spiropyrrolizines
(8) as white solid. The purity of 8 was checked using TLC and 1H NMR
techniques.
Supplementary data associated with this article can be found, in
100-Carbonyl(spiro[2.30]5-chlorooxindole-hexahydro-1H-pyrrolizine)-300,500-bis[(E)-
4-methylphenylmethylidene]tetrahydro-400(1H)-pyridinones (8h): White solid;
References and notes
(0.139 g, 85%); mp 173–175 °C; IR (KBr)
m ;
max: 3428, 1700, 1641 cmꢀ1 1H
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2.06 (m, 1H, H-5), 2.16–2.22 (m, 1H, H-4), 2.35 (s, 6H, CH3), 2.42–2.47 (m, 1H,
H-7), 2.49–2.57 (m, 2H, H-4, H-7), 3.90 (dd, J = 12.09, 7.09 Hz, 1H, H-3), 3.98–
4.10 (m, 2H, H-4a, H-600), 4.53 (d, J = 16.50, 1H, H-200), 4.59 (d, J = 16.50, 1H, H-
200), 5.06 (d, J = 15.60 Hz, 1H, H-600), 6.63–7.29 (m, 9H, H-Aromatic), 7.53 (s, 1H,
H-arylmethylidene), 7.65 (s, 1H, H-arylmethylidene), 7.84 (s, 1H, NH). 13C NMR
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31. Crystallographic data (excluding structure factors) for spiro-pyrrolizine 8h in
this Letter have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 908117. Copies of the data
can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44 (0)1223 336033 or e-mail:
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