Bromodimethylsulfonium bromide: A novel reagent for the one pot synthesis of potent Nα-ureido peptides and study of molecular docking and antibacterial activities

Document Type : Article

Authors

1 Dept. of Chemistry, SIT, Affiliated to VTU, Tumakuru. Karntaka. India

2 Dept. of Chemistry, S.I.T., Tumakuru, Karnataka, INDIA

3 Dept. of Biotechnolgy, S.I.T., Tumakuru, Karnataka, INDIA

Abstract

Nα-protected ureidopeptides were synthesized efficiently using Bromodimethylsulfonium bromide mediated Curtius rearrangement through the in-situ generation of carboxylated sulfonium intermediate. Conversion of carboxylic acids to ureidopeptides in good yield was obtained in one-pot under mild reaction conditions, through a simple workup. To check the binding modes and binding affinity of urea functional group with target protein, the synthesized compounds were subjected to docking studies. Docking scores confirm that the molecules Boc-Leu-ψ[NHCONH]-Ala-OMe and Leu-ψ[NHCONH]-Ala-OMe have least energy and good agreement with the results of antibacterial studies against Escherichia coli, Staphylococcus aureus and Pseudomonas aeroginosa with respect to Streptomycin sulphate as a standard. The synthesized compounds were well characterized by IR, 1H NMR, 13C NMR and mass spectral studies.

Keywords

Main Subjects


References
1. Omar, I.B., Refat, M.S., Salman, M.A.L., and Majthoub,
M.M. Chemical studies on the uses of urea
complexes to synthesize compounds having electrical
and biological applications", Int. J. Mat. Sci., 2, pp.
67-82 (2012).
2. Sharwan, K.D. and Rashmi Synthesis of N, N'-
disubstituted ureas from biuret and anilines", J. Appl.
Chem., 3, pp. 1011-1014 (2014).
M. Raghavendra et al./Scientia Iranica, Transactions C: Chemistry and ... 25 (2018) 3311{3321 3319
3. Isabelle, G. Unsymmetrical ureas. Synthetic methodologies
and application in drug design", Org. Prep. and
Proce. Int., 39, pp. 355-383 (2000).
4. Sanjay, B., Zehra, T., and Sudharshan, M. Medicinal
chemistry of ureido derivatives as antiinfectives", Anti-
Infe. Agent in Med. Chem., 5, pp. 135-160 (2006).
5. Nagireddy, V.R., Pailla, S.K., Peddi, S.R., Kantam,
M.L., and Kallu, R.R. Synthesis of unsymmetrical
phenylurea derivatives via oxidative cross coupling
of aryl formamides with amines under metal free
conditions", New J. Chem., 37, pp. 1-3 (2013).
6. Koyo, M. ACAT inhibitors as antiatherosclerotic
agents: Compounds and mechanisms", Med. Res. Rev.,
14, pp. 271-305 (1994).
7. Nicholas, H.C., Paul, E.A., Lee, T.B., Chong-Hwan,
C., Charles, J.E., Sena, G., Mary, G., David, A.J.,
Prabharkar, K.J., Bruce, K., Patrick, Y.S.L., Michael,
B.M.L., and Susan, E.V. Improved cyclic urea inhibitors
of the HIV-1 protease: synthesis, potency,
resistance pro le, human pharmacokinetics and Xraycrystal
structure of DMP 450", Chem. and Bio.,
3, pp. 301-314 (1996).
8. James, L.M., Michael, J.O., Marlene, M.R., Carol, R.,
Thomas, R.S., Linyee, S., Dean, P.G.B., Mojgan, A.T.,
Delia, P., Andrea, B., Romeo, R., Francesca, F., Naser,
A., Allan, R.M., Katia, V., Stefania, G., Stefania,
M., and Pier, A.B. Design, synthesis, and biological
evaluation of new 8-heterocyclic xanthine derivatives
as highly potent and selective human A2B adenosine
receptor antagonists", J. Med. Chem., 47, pp. 1434-
1447 (2004).
9. Khalid, M.K., Sumayya, S., Muhammad, A., Madiha,
G., Javariya, Z., and Ambreen, K. Unsymmetrically
disubstituted urea derivatives: A potent class of
antiglycating agents", Bioorg. & Med. Chem., 17, pp.
2447-2451 (2009).
10. Peter, S.D., John, E.B., Judy, F., Michael, I., Vincent,
J.K., Charles, R.K., Daniel, R.K., Cristina, T.L.,
Ellen, W.M., Hans, E., Laura, A.K.P., Thomas, J.P.,
Richard, E.S., John, H.T., Kathleen, D.T., and Ernest,
V.J. Structure-based design of novel, urea-containing
FKBP12 inhibitors", J. Med. Chem., 39, pp. 1872-
1884 (1996).
11. Pawel, D. and Dawid, L.J.J. Amide and ureafunctionalized
pyrroles and benzopyrroles as synthetic,
neutral anion receptors", Chem. Soc. Rev., 40, pp.
2971-2985 (2011).
12. Sebastien, F., Emmanuel, M., Jacques, L., Jean,
C.T., Alexandre, P., and Rene, C.G. N-phenyl-N0-(2-
chloroethyl) urea analogues of combretastatin A-4: Is
the N-phenyl-N0-(2-chloroethyl)urea pharmacophore
mimicking the trimethoxy phenyl moiety", Bioorg. and
Med. Chem. Lett., 17, pp. 2000-2004 (2007).
13. Douglas, S.J., Cory, S., Scott, E.L., Suzanne, R.K.,
Lorraine, K.F., Mark, M., David, B., Marya, B.L.,
Sarah, E.S., David, T.D., Nalini, S., Shobha, N.B.,
Stephen, J.K., Tyzoon, K.N., Benjamin, F.C.A., and
Kay A highly potent, orally bioavailable, and selective
urea FAAH inhibitor", ACS Med. Chem. Lett., 2, pp.
91-96 (2011).
14. Dan, Z., Sonawane, N.D., Marc, H.L., and Baoxue, Y.
Comparative transport eciencies of urea analogues
through urea transporter UT-B", Biochimi. Biophy.
Acta., 1768, pp. 1815-1821 (2007).
15. Paul, S.C., Anne, L.G., Trudy, H.G., Jonathan, D.P.,
Michael, B., Steve, B., David, D.D., Joseph, E.D.,
Christian, H.G., Arnaud, L.T., Yusheng, L., Nagraj,
M., David, P.N., Emanuele, P., Steven, R., Dean,
S., Lora, L.S., Qing, T., Pamela, R.T., Ski-Kai, T.,
Martin, T., Tiansheng, W., Yunyi, W., Hong, Z.,
and Dean, S. Novel dual-targeting benzimidazole urea
inhibitors of DNA gyrase and topoisomerase IV possessing
potent antibacterial activity: Intelligent design
and evolution through the judicious use of structureguided
design and structure-activity relationships", J.
Med. Chem., 51, pp. 5243-5263 (2008).
16. Vijay, K.D.N., Hadianawala, M., Sahishna, P., Shweta,
S., Naidu, V.G.M., Satheesh, K.N., and Krishnam,
R.A. Design, synthesis, and biological evaluation
of 4-(1-(4(sulphanilamide)phenyl)-3-(methyl)-
1H-pyrazol-5-yl)dine urea and N-acyl derivatives as
a soluble epoxide hydrolase inhibitors", Med. Chem.
Res., 23, pp. 2178-2197 (2014).
17. Olga, R. and Ratner, S. E ects of analogues of
aspartic acid on enzymes of urea synthesism", Arch.
Biochem. and Biophys., 127, pp. 688-704 (1968).
18. Valeria, A., Luigi, F., and Lorenzo, M. Anion recognition
by hydrogen bonding: urea-based receptors",
Chem. Soc. Rev., 39, pp. 3889-3915 (2010).
19. Radu, C. Crystal engineering with urea and thiourea
hydrogen-bonding groups", Chem. Commun., pp. 295-
307 (2008).
20. Sureshbabu, V.V. and Rao, V. Synthesis of ureidopeptides
using penta
uorophenyl carbamates from
N03b1-Fmoc-peptide acids", Ind. J. Chem., 47B, pp.
910-919 (2008).
21. Narendra, N., Gundala, C., and Sureshbabu, V.V.
Application of carbodiimide mediated Lossen rearrangement
for the synthesis of 03b1-ureidopeptides
and peptidyl ureas employing N-urethane 03b1-
amino/peptidyl hydroxamic acids", Org. Biomol.
Chem., 7, pp. 3520-3526 (2009).
22. Sureshbabu, V.V., Lalithamba, H.S., Narendra, N.,
and Hemantha, H.P. New and simple synthesis of
acid azides, ureas and carbamates from carboxylic
acids: application of peptide coupling agents EDC and
HBTU", Org. Biomol. Chem., 8, pp. 835-840 (2010).
23. Kazuyoshi, T., Yoshie, A., Atsuko, S., Toshiko, T.,
and Haruo, O. Convenient methods for syntheses of
active carbamates, ureas and nitrosoureas using N,N0-
3320 M. Raghavendra et al./Scientia Iranica, Transactions C: Chemistry and ... 25 (2018) 3311{3321
disuccinimido carbonate", Tetrahedron Lett., 24, pp.
4569-4572 (1983).
24. Chennakrishnareddy, G., Vishwanatha, T.M., and
Sureshbabu, V.V. One-pot synthesis of ureido peptides
and urea-tethered glycosylated amino acids employing
deoxo-
uor and TMSN3", Synlett., 3, pp. 407-
410 (2009).
25. Narendra, N., Sureshbabu, V.V., and Kantharaju
Penta
uorophenyl(tert-butoxycarbonylamino)methyl
carbamates: Synthesis, isolation and application to
the synthesis of ureidopeptides", Ind. J. Chem., 48,
pp. 920-926 (2008).
26. Shaabani, A. and Maleki, A. Three-component, onepot
synthesis of 3, 4-dihydropyrimidin-2-(1H)-ones catalyzed
by bromodimethylsulfonium bromide", Chem.
Pa., 61, pp. 333-336 (2007).
27. Meerwein, H., Zenner, K.F., Gipp, R., and Justus, L.
Chlor-dimethyl-sulfoniumsalze", Ann. Chem., 688,
pp. 67-67 (1965).
28. Das, B., Krishnaiah, M., and Venkateswarlu, K.
Highly regioselective ring opening of epoxides and
aziridines using bromodimethylsulfonium bromide",
Tetrahedron Lett., 47, pp. 4457-4460 (2006).
29. Yuan, L.C. and Bert, H.B. The electrophilic addition
of dimethylbromosulfonium bromide to conjugated
enones: ecient synthesis of -bromo enones", Can.
J. Chem., 60, pp. 2268-2273 (1982).
30. Abu, T.K., Ejabul, M., Ballav, M.B., and Subrata,
G. A highly ecient and chemoselective synthetic
protocol for tetrahydropyranylation/depyranylation of
alcohols and phenols", Eur. J. Org. Chem., 2003, pp.
4113-4117 (2003).
31. Satavisha, S., Jugal, K.R.D., Jagadish, P.H., and
Abu, T.K. Bromodimethylsulfonium bromide catalyzed
synthesis of 1, 5-benzodiazepines using a multicomponent
reaction strategy", Synlett., 24, pp. 2601-
2605 (2013).
32. Sucheta, K. and Vittal, R.B. Bromodimethyl sulfonium
bromide: an inexpensive reagent for the solventfree,
one-pot synthesis of -amino phosphonates",
Tetrahedron Lett., 46, pp. 1209-1210 (2005).
33. Abu, T.K., Sidick, B.R., and Mohan, L. Bromodimethylsulfonium
bromide catalyzed synthesis of
2, 3-unsaturated-O-glycosides via Ferrier rearrangement",
Arkivoc., ii, pp. 201-212 (2012).
34. Biswanath, D., Ramu, R., Ravikanth, B., and Saidi,
R.V. Bromodimethylsulfonium bromide: An e-
cient catalyst for solvent free synthesis of 1, 5-
benzodiazepines", J. Mol. Cat., 246, pp. 76-78 (2006).
35. Lal, D.S.Y., Vishnu, P.S., and Rajesh, P. Bromodimethylsulfonium
bromide: a useful reagent for
conversion of aldoximes and primary amides to nitriles",
Tetrahedron Lett., 50, pp. 5532-5535 (2009).
36. Sarifuddin, G. and Rajakumar, A.K. Bromodimethylsulfonium
bromide as a potential candidate for photocatalytic
selective oxidation of benzylic alcohols using
oxygen and visible light", RSC Adv., 2, pp. 7781-7787
(2012).
37. Batool, A. and Alireza, P. Bromodimethylsulfonium
bromide/tetrabutylammonium nitrite: an ecient catalyst
mixture for the nitration of phenols", Turk. J.
Chem., 34, pp. 753-759 (2010).
38. Lal, D.S.Y., Rajesh, P., and Vishnu, P.S. Bromodimethylsulfonium
bromide-ZnCl2: A mild and ef-
cient catalytic system for Beckmann rearrangement",
Synthesis, 11, pp. 1771-1776 (2010).
39. Abu, T.K., Sidick, B.R., Mohan, L., and Mohammad,
H.M. Formation of unexpected -amino amidine
through three-component UGI condensation reaction",
RSC Adv.,2, pp. 5506-5509 (2012).
40. Ding, N., Chun, Y., Zhang, W., and Li, Y. Bromodimethylsulfonium
bromide catalyzed synthesis of
methyl 2-dexoy-4, 6-O-benzylidene galactopyranoside
from galactal and the rapid route to 2,3- and 2,6-
dideoxygalactopyranoses", Chin. J. Chem., 30, pp.
409-412 (2012).
41. Abu, T.K. and Musawer, K.M. Bromodimethylsulfonium
bromide mediated dithioacetalization of carbohydrates
under solvent-free conditions", Carbohyd. Res.,
345, pp. 2139-2145 (2010).
42. Deepak, K.Y., Arvind, K.Y., Vishnu, P.S., Geeta, W.,
and Lal, D.S.Y. Bromodimethylsulfonium bromide
(BDMS)-mediated Lossen rearrangement: synthesis of
unsymmetrical ureas", Tetrahedron Lett., 53, pp. 2890-
2893 (2012).
43. Xiayang, Q., Sherin, A.M.S., Cheryl, J.A., Robert,
C.I., Martin, S., and David, P.J. Molecular basis for
triclosan activity involves a
ipping loop in the active
site", Prot. Sci., 8, pp. 2529-2532 (1999).
44. David, S., Caroline, M., Johannes, B.G., Sonja, S.,
Kay, D., Heiko, M.M., Wolfram, W., and Valentin, W.
Structural basis of multivalent binding to wheat germ
agglutinin", J.A.C.S., 132, pp. 8704-8719 (2010).
45. Yongcheng, S., Chia, I.L., Fu-Yang, L., Joo Hwan,
N., Mary, H., Yi-Liang, L., Wen-Yih, J., Jennifer,
L., George, L.Y., Victor, N., Andrew, W.H.J., and
Eric, O. Inhibition of staphyloxanthin virulence factor
biosynthesis in staphylococcus aureus: In vitro, in
vivo, and crystallographic results", J. Med. Chem., 52,
pp. 3869-3880 (2009).
46. Berman, H., Henrick, K., and Nakamura, H. Announcing
the worldwide protein data bank", Nat. New
Biol., 10, pp. 980-980 (2003).
47. Jianbin, Y., Chi, Z., Min, G., Zhiyan, B., Weiguo,
Z., Tiancong, Q., Zhiwei, C., Wen, P., Haibin, L.,
Fajun, N., Zhao, W., and Daoxin, X. The arabidopsis
CORONATINE INSENSITIVE1 protein is a
jasmonate receptor", The Plant Cell., 21, pp. 2220-
2236 (2009).
48. Jiang, Xiang, R., Pan, W.C.S., and Bao, T.Z. Synthesis
of novel estrogen receptor antagonists using metalcatalyzed
coupling reactions and characterization of
their biological activity", J. Med. Chem., 56, pp. 2779-
2790 (2013).
M. Raghavendra et al./Scientia Iranica, Transactions C: Chemistry and ... 25 (2018) 3311{3321 3321
49. Nakao, N., Toshifumi, B., Shinich, N., and Michikazu.
Meta-diamide insecticides acting on distinct sites of
RDL GABA receptor from those for conventional noncompetitive
antagonists", Insect Biochem. and Mol.
Bio., 43, pp. 366-375 (2013).
50. Cousins K.R. Computer review of chem draw ultra
12.0.", J.A.C.S., 133, p. 8388 (2011).
51. Naika, H.R., Krishna, V., Lingaraju, K., Chandramohan,
V., Manjunath, D., Navya, P.N., and Suresh, D.
Molecular docking and dynamic studies of bioactive
compounds from naravelia zeylanica (L.) DC against
glycogen synthase kinase-3 protein", J. Taibah Uni.
for Sci., 9, pp. 41-49 (2015).
52. Krajacic, M.B., Novak, P., Dumic, M., Cindric, M.,
Paljetak, H.C., and Kujundzic, N. Novel ureas and
thioureas of 15-membered azalides with antibacterial
activity against key respiratory pathogens", Eur. J.
Med. Chem., 44, pp. 3459-3470 (2009).
53. Uma, K., Lalithamba, H.S., Raghavendra, M., Chandramohan,
V., and Anupama, C. Synthesis of Naprotected
aminoacid/peptide Weinreb amides employing
N,N'-carbonyldiimidazole as activating agent;
studies on docking and antibacterial activities",
Arkivoc., iv, pp. 339-351 (2016).

Volume 25, Issue 6
Transactions on Chemistry and Chemical Engineering (C)
November and December 2018
Pages 3311-3321
  • Receive Date: 14 August 2017
  • Revise Date: 25 November 2017
  • Accept Date: 14 May 2018