A facile approach to the synthesis of structurally diverse 6,8a-dihydropyrido[2,3-d]pyrimidine derivatives via a three-component domino reaction

Article abstract of DOI:10.1039/c5ob01484k

A concise and efficient approach to the synthesis of structurally diverse 6,8a-dihydropyrido[2,3-d]pyrimidine derivatives has been accomplished by a three-component reaction involving sulfonyl acetonitrile, an aromatic aldehyde, and 6-aminouracil. The met

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A facile approach to the synthesis of structurally
diverse 6,8a-dihydropyrido[2,3-d]pyrimidine
derivatives via a three-component domino reaction
Cite this: DOI: 10.1039/x0xx00000x
Yuvaraj Dommaraju,a,b Shruti Bora,a and Dipak Prajapati a,b*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Flight in Nature Reviews Drug Discovery,9 highlighted the work of
A
concise and efficient approach to the synthesis of
Stover et al.10 where 1.6 million compounds from Pfizer compound
library were screened for antibacterial activity. This study resulted in
the finding of three pyrido[2,3ꢀd]pyrimidine derivatives as potent
synthetic antibacterials, that selectively targeted the biotin
carboxylase of bacteria. Also, substances that contains the
pyrido[2,3ꢀd]pyrimidine framework have other stimulating
structurally diverse 6,8a-dihydropyrido[2,3-d]pyrimidine
derivatives has been accomplished by a three-component
reaction involving sulfonyl acetonitrile, an aromatic aldehyde,
and 6-aminouracil. The method involves domino Knoevenagel
condensation/Michael addition/ cyclization cascade in the
presence of triethylamine in refluxing ethanol.
biological
properties
such
as
anticardiovascular,11
antihypersensitive,12 antiꢀinflammatory,13 antifolate,14 insecticidal,15
and antiviral16 activities. Due to the biological activities of
compounds bearing pyrimidine moieties7 deserve the synthesis of
resourceful analogues. A plethora of methods17 have been reported
for the synthesis of pyrido[2,3ꢀd]pyrimidines and related
compounds. As part of our continued research interest towards the
development of highly expedient multicomponent reactions for the
synthesis of diverse pyrimidine containing heterocyclic compounds
of biological importance,18 we report herein the synthesis of a novel
class of structurally diverse 6,8aꢀdihydropyrido[2,3ꢀd]pyrimidine
derivatives using a threeꢀcomponent oneꢀpot protocol under mild
reaction conditions.
Introduction
The development of reliable and highly selective Multicomponent
reactions (MCRs), continues to be an important challenge in organic
synthesis, especially, in the synthesis of diversely substituted
molecular scaffolds in the field of biologically active compounds
and natural product chemistry.1 Compared with stepꢀbyꢀstep
transformations, MCRs provide complex molecular architecture
from simple and readily available starting materials with a high
degree of selectivity and diversity.2 Generally, the selectivity in
MCRs can be affected by various factors, such as catalysts, ligands,
reaction conditions, additives, or the structural features of the
reactants. In this regard, MCRs have been used extensively in the
construction of innumerable chemical libraries. For example, Yan
and coꢀworkers developed several MCRs, which showed the role of
catalyst, solvent, substrates to generate molecular diversity.3 In
particular, the generation of molecular diversity by varying the
structural features of the reactants are emerging as an efficient tool
towards the synthesis of novel heterocyclic compounds.4
Pyrimidines have been recognized as an important class of
heterocyclic compounds and widely studied by the chemists as well
as biologists, due to its presence in numerous natural products and
structurally diverse synthetic derivatives.5 Among pyrimidineꢀ
containing compounds, fused pyrimidines, particularly pyrido[2,3ꢀ
d]pyrimidine derivatives are found in a large variety of substances
that exhibit important biological activities.6 For example, this
heterocyclic structural motif is present in several protein kinase
Scheme 1. Threeꢀcomponent reaction of 1,3ꢀdimethylꢀ6ꢀaminouracil
1a, phenylsulfonyl acetonitrile 2a, and 4ꢀmethylbenzaldehyde 3a.
inhibitors such as AZD8055,
a selective ATPꢀcompetitive
mammalian target of rapamycin kinase inhibitor, used for the
treatment of antitumor,7 piritrexim, a lipophilic inhibitor of the
human dihydrofolate reductase (DHFR) that displays high potency
for the treatment of metastatic urothelial cancer.8 Recently, M. H.
Results and discussion
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DOI: 10.1039/C5OB01484K
We Initiated our study by choosing 1,3ꢀdimethylꢀ6ꢀaminouracil 1a, (Table 1, entries 9). We also performed the model reaction in the
phenylsulfonyl acetonitrile 2a, and 4ꢀmethylbenzaldehyde 3a as absence of the catalyst, but this attempt failed to afford the product
model substrates. In a typical experiment, 1a (1 mmol), 2a (1 mmol) 4a (Table 1, entry 6). Thus, we chose triethylamine and ethanol as
and 3a (1 mmol) were refluxed in 8 mL of dimethylformamide the best catalyst and solvent for the reaction of 6ꢀaminouracil 1,
(DMF) by using triethylamine (30 mmol%) as a catalyst (Scheme 1). alkylsulfonyl acetonitrile 2, and aromatic aldehyde 3.
In contrast to earlier reports,19 we obtained the unexpected 7ꢀaminoꢀ With the optimised reaction conditions, we then explored the
1,3ꢀdimethylꢀ6ꢀ(phenylsulfonyl)ꢀ5ꢀ(pꢀtolyl)ꢀ6,8aꢀdihydropyrido[2,3ꢀ
generality of the method for the synthesis of 6,8aꢀdihydropyrido[2,3ꢀ
d]pyrimidineꢀ2,4(1H,3H)ꢀdione 4a in 61% yield (Table 1, entry 1) d]pyrimidines 4 by employing differently substituted aromatic
within 4 hours. To the best of our knowledge, no method for the aldehydes 3 (Table 2). As shown in Table 2, the aromatic aldehydes
synthesis of 6,8aꢀdihydropyrido[2,3ꢀd]pyrimidine core have been bearing electronꢀwithdrawing groups such as bromo, chloro, fluoro,
reported in the literature yet.
and nitro gave better yields than with electronꢀreleasing groups.
However, this transformation with heteroaromatic and aliphatic
aldehydes such as indoleꢀ3ꢀcarbaldehyde, thiopheneꢀ2ꢀcarbaldehyde,
furanꢀ2ꢀcarbaldehyde and acetaldehyde failed to give compound 4
even after 10 hours of reflux.
Table 1. Optimization conditions for the synthesis of 6,8aꢀ
dihydropyrido[2,3ꢀd]pyrimidine derivative 4a.a
Table 2. The generality of the method for the synthesis of 6,8aꢀ
dihydropyrido[2,3ꢀd]pyrimidine derivative 4a – 4s.a
Entry
Solvent
(8 mL)
DMF
acetonitrile
ethanol
methanol
water
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
ethanol
Catalyst
(30 mol%)
NEt3
Time
(hours)
Yield
(%)b
61
65
67
66
10
ꢀc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
4
4
4
4
6
7
7
7
7
4
5
5
5
6
6
7
6
6
4
NEt3
NEt3
NEt3
NEt3
ꢀ
InCl3
PTSA
ꢀc
ꢀc
Lꢀproline
piperidine
pyrrolidine
DABCO
DBU
morpholine
DMAP
Pyridine
NaOH
K2CO3
NEt3
trace
62
58
55
57
61
52
ꢀc
51
48
68d
aReaction conditions: 1,3ꢀdimethylꢀ6ꢀaminouracil 1a (1 mmol),
phenylsulfonyl acetonitrile 2a (1 mmol)
,
and 4ꢀ
b
methylbenzaldehyde 3a (1 mmol) were used. Isolated yield.
d
cProduct not observed. Reaction was carried out in 10 mmol
scale (50 mL of ethanol was used as solvent).
In order to optimize the reaction conditions, we investigated various
solvents, base, and acid catalysts. Among the all solvents (Table 1,
entries 1–5), ethanol provided the best yield (Table 1, entries 3), and
the workꢀup of the reaction was more convenient with ethanol. The
reaction proceeded smoothly to afford product 4a when 30 mol% of
organic bases such as piperidine, pyrrolidine, DABCO, DBU,
morpholine, DMAP were used as catalysts (Table 1, entries 10–15).
Even inorganic bases like NaOH and K2CO3 were also provided the
product 4a, but with less yield in comparison with organic bases
(Table 1, entries 17, 18). When pyridine was used as a base catalyst,
we afforded the Knoevenagel condensed product of 2a and 3a, but
not 4a (Table 1, entries 16). The reaction failed to give the product
4a when we applied the acid catalysts such as InCl3, PTSA instead
base catalysts (Table 1, entries 7, 8). The reaction afforded only trace
product in the presence of Lꢀproline, even after 7 hours of reflux
aReaction conditions: 6ꢀaminouracil
acetonitrile 2a (1 mmol) and aromatic aldehyde
were used. bIsolated yield.
1
(1 mmol), phenylsulfonyl
(1 mmol)
,
3
We further extended our study with different alkylsulfonyl
acetonitriles 2b-e, to explore the feasibility of the reaction. This
protocol accepts a variety of alkylsulfonyl acetonitriles, where alkyl
group can be an aromatic, heteroaromatic, and aliphatic group,
obtained results are summarized in Table 3. Surprisingly the reaction
2 | J. Name., 2012, 00, 1-3
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proceeded smoothly with the heteroaromatic 2ꢀ(thiophenꢀ2ꢀ
ylsulfonyl)acetonitrile 2d and aliphatic 2ꢀ
(methylsulfonyl)acetonitrile 2e to give the product 4v and 4w. It
indicates that the alkyl substituents attached to sulfonyl functional
group don’t have the negative effect towards the formation of the
product 4 as like heteroaromatic aldehydes. But the alkyl groups
attached to sulfonyl functional group has shown significant change
in the yield of the product. The structure of 6,8aꢀdihydropyrido[2,3ꢀ
d]pyrimidine derivatives 4 were assigned by IR, mass, 1H NMR, and
13C NMR spectra.
Table 3. The feasibility of the method with alkylsulfonyl
acetonitriles for the synthesis of 6,8aꢀdihydropyrido[2,3ꢀ
d]pyrimidine derivatives 4t – 4w.a
Scheme 2. Plausible mechanism for the formation of 4.
To support our mechanistic postulate, a two component reaction was
carried out between the Knoevenagel condensation product 5a
(synthesized from phenylsulfonyl acetonitrile 2a and 4ꢀmethyl
benzaldehyde 3a) and 6ꢀaminouracil 1a under the similar reaction
conditions (Scheme 3). As expected, the derivative 4a was obtained
in comparable yield (65%). We further confirmed our mechanistic
postulate by monitoring the model threeꢀcomponent reaction (by thin
layer chromatography) at different time intervals and observed a spot
corresponds to Knoevenagel condensation product 5a appeared with
Rf value 0.75 (ethyl acetate:hexane 2:8) within 30 minutes. These
experiments supports our assumption that the experimental results
were highly consistent with the proposed mechanism.
aReaction conditions: 1,3ꢀdimethylꢀ6ꢀaminouracil 1a (1 mmol),
alkylsulfonyl acetonitrile
2
(1 mmol)
,
and 4ꢀmethyl
benzaldehyde 3a (1 mmol) were used. bIsolated yield.
For example, the mass spectrum of 4g showed a molecular ion peak
at m/z = 460.1, which is corresponding with the proposed structure.
In the IR spectrum of 4g, two absorptions at 3399 and 3356 cm–1
attributed to NH2, and other absorption bands at 1632, 1595, 1499,
1450, 1384, 1352, 1302, 1213, 789 cm–1, related to C=O, C=C, SO2,
and C–Cl stretching vibrations, indicating the most significant
functional groups in the product. The 1H NMR spectrum of 4g
exhibited two singlets at δ = 8.71 and 8.33 ppm (exchangeable with
deuterium), which can be assigned to the NH2 group. Nine aromatic
hydrogen signals resonate as two multiplets at δ = 7.72 – 7.65, 7.56
–7.49 ppm, two triplets at δ = 7.29, 7.19 ppm, and one doublet at δ =
6.79 ppm. The resonance for the two CH protons appeared as
singlets at δ = 4.97, 4.36 ppm. Remaining six Nꢀmethyl hydrogens
Scheme 3. Stepwise experiments for the synthesis of 4a.
Conclusions
1
appeared at δ = 3.04 ppm as a singlet. The Hꢀdecoupled 13CꢀNMR
In conclusion, we have demonstrated a facile and efficient oneꢀ
pot, threeꢀcomponent reaction strategy for the synthesis of
spectrum of 4g showed 19 distinct resonances, Nꢀmethyl groups in
the pyrimidine ring appear at δ = 29.61, 27.64 ppm and two
significant SP3 carbons in the pyridine ring showed signals at δ =
34.05, 66.00 ppm. The most important resonance for amidine carbon
appeared at δ = 159.02 ppm, and the peaks at δ = 160.932, 154.65
ppm indicates two amide carbonyl carbons. The described analytical
data of 4g confirmed the proposed structure.
A plausible mechanism for the synthesis of 6,8aꢀdihydropyrido[2,3ꢀ
d]pyrimidine derivatives 4 has been proposed in Scheme 2. It is
assumed that Knoevenagel condensation product A is formed
between alkylsulfonyl acetonitrile 2 and aromatic aldehyde 3 which
then participates in Michael addition with 6ꢀaminouracil 1 to form
the Michael adduct B. Then the formed Michael adduct B undergoes
intramolecular cyclization to produce intermediate C. A subsequent
1,3ꢀproton shift of the intermediate C forms the final product 4.
structurally
derivatives.
diverse
6,8aꢀdihydropyrido[2,3ꢀ
d
d
]pyrimidine
]pyrimidine
A
novel class of pyrido[2,3ꢀ
derivatives were obtained in good to excellent yields from this
atomꢀeconomical procedure without the requirement of the
traditional column chromatography. The present method
provides large substrate scope, tolerated a variety of aromatic
aldehydes, 6ꢀaminouracils, and alkylsulfonyl acetonitriles.
Further, we believe that our developed methodology can be
regarded as a valuable protocol for production of novel
pyrido[2,3ꢀd]pyrimidine derivatives and will create interest
among chemists towards the synthesis of combinatorial
libraries.
Acknowledgements
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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5OB01484K
We thank CSIR, New Delhi for financial support to the
Network project. YD thanks UGC, New Delhi for the award of
a research fellowship. We also thank the Director, CSIRꢀ
NEIST, Jorhat, for his keen interest and constant
encouragement.
885ꢀ898; (c) J. Matsumoto and S. Minami, J. Med. Chem., 1975, 18
,
74ꢀ79.
7
C. M. Chresta, B. R. Davies, I. Hickson, T. Harding, S. Cosulich, S.
E. Critchlow, J. P. Vincent, R. Ellston, D. Jones, P. Sini, D. James, Z.
Howard, P. Dudley, G. Hughes, L. Smith, S. Maguire, M.
Hummersone, K. Malagu, K. Menear, R. Jenkins, M. Jacobsen, G. C.
M. Smith, S. Guichard and M. Pass, Cancer Res., 2010, 70, 288ꢀ298.
(a) M. Zink, H. Lanig and R. Troschutz, Eur. J. Med. Chem., 2004,
39, 1079ꢀ1088; (b) R. de Wit, S. B. Kaye, J. T. Roberts, G. Stoter, J.
Scott and J. Verweij, Br. J. Cancer, 1993, 67, 388ꢀ390.
Notes and references
aMedicinal Chemistry Division, CSIR-North-East Institute of Science and
Technology, Jorhat, Assam 785006, India.
bAcadamy of Scientific and Innovative Research, New Delhi, India
Fax: +91 376 2370011;
8
9
M. H. Flight, Nat. Rev. Drug Disc., 2011, 10, 577ꢀ577.
E-mail: dr_dprajapati2003@yahoo.co.uk.
10 J. R. Miller, S. Dunham, I. Mochalkin, C. Banotai, M. Bowman, S.
Buist, B. Dunkle, D. Hanna, H. J. Harwood, M. D. Huband, A.
Karnovsky, M. Kuhn, C. Limberakis, J. Y. Liu, S. Mehrens, W. T.
Mueller, L. Narasimhan, A. Ogden, J. Ohren, J. V. N. V. Prasad, J. A.
Shelly, L. Skerlos, M. Sulavik, V. H. Thomas, S. VanderRoest, L.
Wang, Z. Wang, A. Whitton, T. Zhu and C. K. Stover, PNAS, 2009,
106, 1737ꢀ1742.
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
1
(a) B. B. Touré and D. G. Hall, Chem. Rev., 2009, 109, 4439ꢀ4486;
(b) A. Dömling, Chem. Rev., 2006, 106, 17ꢀ89; (c) L. F. Tietze and
A. Modi, Med. Res. Rev., 2000, 20, 304ꢀ322; (d) G. H. Posner, Chem. 11 O. Fjellström, J. Deinum, T. Sjögren, C. Johansson, S.
Rev., 1986, 86, 831ꢀ844.
Geschwindner, V. Nerme, A. Legnehed, J. McPheat, K. Olsson, C.
2
(a) J. Zhu, Q. Wang and M. X. Wang, Multicomponent Reactions in
Organic Synthesis, Wiley Blackwell, 2015; (b) S. Brauch, S. S. van
Bodin, A. Paunovic and D. Gustafsson, J. Biol. Chem., 2013, 288,
873ꢀ885.
Berkel and B. Westermann, Chem. Soc. Rev., 2013, 42, 4948ꢀ4962; 12 C. J. Blankley, L. R. Bennett, R. W. Fleming, R. D. Smith, D. K.
(c) J. Zhu and H. Bienaymé, Multicomponent Reactions, John Wiley
and Sons, 2005.
Tessman and H. R. Kaplan, J. Med. Chem., 1983, 26, 403ꢀ411.
13 (a) S. S. Laddha and S. P. Bhatnagar, Bioorg. Med. Chem., 2009, 17
,
3
(a) H. Gao, J. Sun and C. G. Yan, Mol. Div., 2014, 18, 511ꢀ519; (b) J.
Sun, D. Zhu, H. Gong and C. G. Yan, Tetrahedron, 2013, 69, 10565ꢀ
10572; (c) J. Sun, Y. Sun, H. Gong, Y. J. Xie and C. G. Yan, Org.
6796ꢀ6802; (b) G. Nam, C. M. Yoon, E. Kim, C. K. Rhee, J. H. Kim,
J. H. Shin and S. H. Kim, Bioorg. Med. Chem. Lett., 2001, 11, 611ꢀ
614.
lett., 2012, 14, 5172ꢀ5175; (d) L. Hui, H. Y. Li and C. G. Yan, Eur. J. 14 W. D. Sedwick, M. Hamrell, O. E. Brown and J. Laszlo, Mol.
Org. Chem., 2012, 3157ꢀ3164; (e) J. Sun, E. Y. Xia, Q. Wu and C. G. Pharmacol., 1982, 22, 766ꢀ770.
Yan, ACS Comb. Sci., 2011, 13, 421ꢀ426; (f) J. Sun, Q. Wu, E. Y. 15 R. E. Heckler, G. P. Jourdan, Eur. Patent, 414 386, 1991; Chem.
Xia and C. G. Yan, Eur. J. Org. Chem., 2011, 2981ꢀ2986; (g) J. Sun, Abstr. 1991, 115, 71630.
Y. Sun, E. Y. Xia and C. G. Yan, ACS Comb. Sci., 2011, 13, 436ꢀ 16 R. B. Tenser, A. Gaydos and K. A. Hay, Antimicrob. Agents
441; (h) L. Hui, Y. X. Jin, J. X. Wang and C. G. Yan, Eur. J. Org.
Chem., 2011, 7194ꢀ7198.
Chemother., 2001, 45, 3657ꢀ3659.
17 (a) A. KhalafiꢀNezhad, M. Divar and F. Panahi, RSC Adv., 2015, 5,
4
(a) N. Poomathi, S. Mayakrishnan, D. Muralidharan, R. Srinivasan
and P. T. Perumal, Green Chem., 2015; (b) D. Bhuyan, M. M.
Sarmah, Y. Dommaraju and D. Prajapati, Tetrahedron Lett., 2014,
55, 5133ꢀ5136; (c) N. Kielland, E. VicenteꢀGarcía, M. Revés, N.
2223ꢀ2230; (b) S. P. Satasia, P. N. Kalaria and D. K. Raval, Org.
Biomol. Chem., 2014, 12, 1751ꢀ1758; (c) A. Rahmati and Z. Khalesi,
Tetrahedron, 2012, 68, 8472ꢀ8479; (d) R. Sarma, K. J. Borah, Y.
Dommaraju and D. Prajapati, Mol. Div., 2011, 15, 697ꢀ705; (e) S.
Samai, G. Chandra Nandi, S. Chowdhury and M. S. Singh,
Tetrahedron, 2011, 67, 5935ꢀ5941; (f) G. Imani Shakibaei, A. Feiz,
H. Reza Khavasi, A. Abolhasani Soorki and A. Bazgir, ACS Comb.
Sci., 2011, 13, 96ꢀ99; (g) X. Berzosa, X. Bellatriu, J. Teixidó and J. I.
Borrell, J. Org. Chem., 2010, 75, 487ꢀ490; (h) A. Shaabani, M.
Seyyedhamzeh, A. Maleki, F. Rezazadeh and M. Behnam, J. Comb.
Chem., 2009, 11, 375ꢀ377; (i) R. Ghahremanzadeh, M. Sayyafi, S.
Ahadi and A. Bazgir, J. Comb. Chem., 2009, 11, 393ꢀ396.
Isambert, M. J. Arévalo and R. Lavilla, Adv. Synth. Catal., 2013, 355
3273ꢀ3284; (d) C. Altug, A. K. Burnett, E. Caner, Y. Dürüst, M. C.
Elliott, R. P. J. Glanville, C. Guy and A. D. Westwell, Tetrahedron
,
,
2011, 67, 9522ꢀ9528; (e) B. Ganem, Acc. Chem. Res., 2009, 42, 463ꢀ
472.
5
(a) V. Sharma, N. Chitranshi and A. K. Agarwal, Int. J. Med. Chem.,
2014, 2014, 31; (b) V. Kumar and M. P. Mahajan, in Heterocycles in
Natural Product Synthesis, WileyꢀVCH Verlag GmbH & Co. KGaA,
2011, pp. 507ꢀ533; (c) E. V. Costa, M. L. B. Pinheiro, C. M. Xavier, 18 (a) N. Rajesh and D. Prajapati, Org. Biomol. Chem., 2015, 13, 4668ꢀ
J. R. A. Silva, A. C. F. Amaral, A. D. L. Souza, A. Barison, F. R.
4672; (b) Y. Dommaraju and D. Prajapati, Mol. Div., 2015, 19, 173ꢀ
Campos, A. G. Ferreira, G. M. C. Machado and L. L. P. Leon, J. Nat.
187; (c) Y. Dommaraju, S. Borthakur, N. Rajesh and D. Prajapati,
Prod., 2006, 69, 292ꢀ294; (d) I. M. Lagoja, Chemistry & biodiversity
2005, , 1ꢀ50; (e) A. Lawen, Bioessays, 2003, 25, 888ꢀ896.
,
RSC Adv., 2015,
Dommaraju and D. Prajapati, Green Chem., 2014, 16, 1158ꢀ1162; (e)
M. M. Sarmah, R. Sarma, D. Prajapati and W. Hu, Tetrahedron Lett.,
5, 24327ꢀ24335; (d) D. Bhuyan, R. Sarma, Y.
2
6
(a) M. N. Nasr and M. M. Gineinah, Arch. Pharm., 2002, 335, 289ꢀ
295; (b) A. J. Kraker, B. G. Hartl, A. M. Amar, M. R. Barvian, H. D.
2013, 54, 267ꢀ271; (f) R. Sarma, M. M. Sarmah and D. Prajapati, J.
Org. Chem., 2012, 77, 2018ꢀ2023.
H. Showalter and C. W. Moore, Biochem. Pharmacol., 2000, 60
,
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19 (a) P. S. Naidu, P. Borah and P. J. Bhuyan, Tetrahedron Lett., 2012,
53, 4015ꢀ4017; (b) A. Agarwal and P. M. S. Chauhan, Tetrahedron
Lett., 2005, 46, 1345ꢀ1348; (c) I. Devi, B. S. D. Kumar and P. J.
Bhuyan, Tetrahedron Lett., 2003, 44, 8307ꢀ8310.
This journal is © The Royal Society of Chemistry 2012
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