Published ArticleIn the present study, we report Yb(OTf)3 catalyzed synthesis of biscoumarins by pseudo
three-component reaction of aldehyde and 4-hydroxycoumarin. The synthesized biscoumarins were evaluated
for antimicrobial and insecticidal activity. Results of antimicrobial activity were found to be moderate
to good in terms of zones of inhibition and MIC values against E. coli, P. vulgaris and S. aureus. The compounds
were inactive against the used fungal strains except B4 in case of Penicillium. Insecticidal activity
of the biscoumarins B-1, B-3, B-5 and B-11 was found to be good exhibiting 70-75% mortality effect on
Callosobruchus maculatus

Dodkeyb, Alaknanda M.

Kendrekarc, Pravin S.

Pawar, Rajendra P.

Tekalea, Sunil U.

Thorea, Shivaji N.

English

Central University Of Technology Free State - LibraryCUT, South Africa

Chemistry & Biology Interface Vol. 8 (1), January – February 201856ISSN: 2249 –4820Yb(OTf)3 Catalyzed Synthesis, Antimicrobial and Insecticidal activity of some BiscoumarinsAbstract: In the present study, we report Yb(OTf)3 catalyzed synthesis of biscoumarins by pseudo three-component reaction of aldehyde and 4-hydroxycoumarin. The synthesized biscoumarins were evalu-ated for antimicrobial and insecticidal activity. Results of antimicrobial activity were found to be moderate to good in terms of zones of inhibition and MIC values against E. coli, P. vulgaris and S. aureus. The com-pounds were inactive against the used fungal strains except B4 in case of Penicillium. Insecticidal activity of the biscoumarins B-1, B-3, B-5 and B-11 was found to be good exhibiting 70-75% mortality effect on Callosobruchus maculatus.Keywords: Yb(OTf)3, Biscoumarins, Antimicrobial, InsecticidalSunil U. Tekalea, Shivaji N. Thorea, Alaknanda M. Dodkeyb, Pravin S. Kendrekarc, Rajendra P. Pawar*aaDepartment of Chemistry, Deogiri College, Station Road, Aurangabad (MS)-431 005, India.bDepartment of Chemistry, S. B. E. S. College of Science, Aurangabad (MS)-431 001, India.cDepartment of Health Sciences, Central University of Technology, Bloemfontein, Free State-9300, South Africa.*Corresponding author Email: rppawar@yahoo.comReceived September-Novemver 2017; Accepted 25 January 2018RESEARCH PAPERCHEMISTRY & BIOLOGY INTERFACEAn official Journal of ISCB, Journal homepage; www.cbijournal.comIntroduction:2H-Chromen-2-one or benzopyran-2-one (1); commonly known as coumarin belongs to benzopyrone class of heterocyclic compounds. Coumarins constitute a biodynamic and significant class of naturally occurring compounds in the realm of natural products and synthetic organic chemistry [1].4-Hydroxycoumarin (2) is a vitamin K antagonist [2]. Dicoumarol (3) is a naturally occurring anticoagulant, inhibitor of reductases and vitamin K deplete [3]. It is a natural compound of plant and fungal origin. O O(1)O OOH(2)OOOH OHOO(3)Coumarin based heterocyclic compounds are well renowned for therapeutic potential as well as many biological activities including Chemistry & Biology Interface, 2018, 8, 1, 56-61Chemistry & Biology Interface Vol. 8 (1), January – February 201857vitamin K antagonists [4], pesticides [5], anti-inflammatory agents [6], anti-coagulants [7] etc. A wide range of biological applications of coumarin based derivatives have intrigued organic and medicinal chemists to explore as drugs. This fact renders them attractive for derivatization and evaluation as novel therapeutic agents. Thus, coumarin related compounds constitute the significant targets in medicinal and pharmaceutical chemistry. Rare earth metal triflates act as water tolerant, mild and efficient catalysts which are well established as environmentally benign Lewis acids particularly useful for green chemistry applications; offering functional group tolerance during reactions. Furthermore, the triflates do not lose their acidity even in the presence of Lewis bases containing oxygen, nitrogen, sulfur and phosphorus atoms. Among commonly used lanthanide metal triflates; ytterbium (III) trifluoromethanesulfonate or ytterbium (III) triflate; abbreviated as Yb(OTf)3 is a water tolerant Lewis acid catalyst useful in many synthetic organic reactions. Recently it has been used in Meerwein-Ponndorf-Verley (MPV) reduction [8], Hantzsch reaction [9], thia-Michael addition to α, β-unsaturated ketones [10], Friedel-Crafts acylation [11], synthesis of α-amino phosphonates [12], substituted lactams [13], β-enaminones [14], benzoxanthenes [15] etc. Considering a wide range of biological activities and therapeutic potential of coumarin derivatives; in the present work we have synthesized some biscoumarins by ytterbium triflate catalyzed reaction of various aldehydes with 4-hydroxy coumarin (Scheme 1). Furthermore, the synthesized compounds were screened for antibacterial, antifungal and insecticidal activities. OO O OOHOHXOOHOOHX 2EtOH, reflux, 1.5-3 h(Scheme 1)Yb(OTf)3 (5 mol%)(a-k)Table 1: Ytterbium triflate catalyzed synthesis of biscoumarinsSr. No. Aldehyde Product CodeTime (h)Yield (%)@ M. P. (oC)1CHO(a) B1 1.5 83 227-229 [22]2CHOF(b) B2 1.5 78 243-2453CHOCF3(c) B3 1.5 74 182-1844CHOFNO2(d) B4 2.0 80 173-1755CHO(e) B5 1.5 87 255-2576CHOMeS(f) B6 1.5 90 225-2277CHOBrF(g) B7 3.0 79 178-1808CHOFBr(h) B8 3.0 74 280-2829CHOOO(i) B9 1.5 85 230-23210CHOOHOMe(j) B10 3.0 78 272-27411 CHOFOH(k) B11 3.0 75 248-250@Reactions were carried on aldehyde (2 mmol) and 4-hydroxycoumarin (4 mmol) in ethanol (5 mL) using Yb(OTf)3 (5 mol%).Materials and Methods: Chemicals used were SD fine or Aldrich made. Melting points of the products were recorded in capillaries open at one end on a digital melting point apparatus (Optics Technology). Progress of the reaction was monitored by TLC (70% ethyl acetate: n-hexane). Antimicrobial activity of the synthesized compounds was carried out by using reported methods. Chemistry & Biology Interface, 2018, 8, 1, 56-61Chemistry & Biology Interface Vol. 8 (1), January – February 201858General procedure for the synthesis of biscoumarins: Yb(OTf)3 (5 mol%) was added to a solution of aldehyde (2 mmol) and 4-hydroxycoumarin (4 mmol) in ethanol (5 mL) and contents were refluxed for the specified time (Table 1). Progress of the reaction was monitored by TLC (70% ethyl acetate: n-hexane). After completion of reaction as indicated by TLC; contents were concentrated under reduced pressure, diluted with water (10 mL) and the precipitated solid was further purified by crystallization with ethanol to afford pure product. The aqueous layer was concentrated in vacuum to give a white crystalline solid as the recovered catalyst which can be recycled.Spectral data of representative compounds is mentioned below:3-[(4-Fluoro-3-nitrophenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)-4-hydroxy-2H-chromen-2-one] (Entry 4, Table 1): M. P. 173-175 oC; 1H NMR (400 MHz, CDCl3) δ ppm 6.19 (s, 1H), 7.15 (d, 1H), 7.36 (d, 5H), 7.6 (t, 2H), 7.8 (d, 1H), 8.0-8.2 (dd, 2H), 11.32 (1H, brs, -OH), 11.70 (1H, brs, -OH), 13C NMR (100 MHz, CDCl3) δ ppm 35.46, 59.57, 103.48, 115.93, 117.73, 123.89, 132.02, 134.67, 136.69, 137.26, 151.68, 152.21, 154.27, 164.74, 165.09; EI-MS: 474.2 (M-1) (Negative mode), 476.2 (M+1) (Positive mode); IR (neat) cm-1 2970.8, 1739.48, 1649.84, 1615.12, 1598.21,1346.45, 762.36.3-[(9H-fluoren-2-yl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-4-hydroxy-2H-chromen-2-one: (Entry 5, Table 1): M. P. 255-257, 1H NMR (400 MHz, CDCl3) δ ppm 3.98 (s, 2H), 6.21 (s, 1H), 7.37 (d, 2H), 7.4-7.54 (m, 7H), 7.6-7.9 (m, 4H), 8.1 (dd, 2H), 11.35 (brs, 1H, -OH), 11.59 (brs, 1H, -OH). 13C NMR (100 MHz, CDCl3) δ ppm 35.97, 36.37, 104.60, 116.04, 117.07, 119.55, 123.27, 123.94, 124.88, 125.43, 126.52, 132.10, 137.53, 139.18, 140.90, 143.04, 152.09, 164.34, 165.14; EI-MS: 499.3 (M-1) (Negative mode), 501.3 (M+1) (Positive mode); IR (neat) cm-1 2981, 1739.44, 1661.93, 1610.22, 1563.54, 1346.65, 755.38.Biological evaluation of biscoumarins:Determination of antibacterial activity:Antibacterial activity was studied by using reported disc diffusion method [16, 17]. Nutrient agar medium was prepared and plated with the microbial cultures - Escherichia coli (gram -ve), Proteus vulgaris (gram -ve) and Staphylococcus aureus (gram +ve), A. Niger, A. Fumigatus and Penicillium.  10-6 CFU/mL (Colony Forming Unit per mL) was inoculated separately on the solidified agar on each petri dish by streaking with the help of a wire loop. Discs (5 mm diameter) were prepared in each of these plates. Solutions of the test compounds were prepared at a concentration of 500 μg/mL and 30 µL of each sample was added onto the disc. Thus prepared plates were kept in refrigerator (4 oC)  for 30 minutes for uniform diffusion of sample into media. The plates were incubated at 37 °C for 24 hr in incubator and the diameter of zone of inhibition was expressed in millimeter (mm) (Table 2).Each sample was assayed in triplicate and the mean values were determined. The efficiency of samples against bacteria was compared with the broad spectrum antibiotic rifampicin and ampicillin (each at 500 μg/mL concentration) by measuring the zone of inhibition. The minimum inhibitory concentration (MIC) is defined as the lowest drug concentration inhibiting bacterial growth which makes the zone of inhibition just visible. The MIC values for selected compounds were determined on solid medium (Nutrient agar) and expressed by average of three assays using Collin’s method [18]. The range of concentration used was 350 ppm-450 Chemistry & Biology Interface, 2018, 8, 1, 56-61Chemistry & Biology Interface Vol. 8 (1), January – February 201859Chemistry & Biology Interface, 2018, 8, 1, 56-61ppm (Table 3).Table 2: Antimicrobial evaluation of biscoumarinsSr. No. Comp. Zone of inhibition (mm)E. ColiP. VulgarisS. AureusA. NigerA. Fumigatus Penicillium1 B1 * * * * * *2 B2 * * * * * *3 B3 * * * * * *4 B4 * * * * * 19 mm5 B5 9 mm * 6 mm * * *6 B6 * * * * * *7 B7 * * * * * *8 B8 11 mm 10 mm 10 mm * * *9 B9 * * * * * *10 B10 * * * * * *11 B11 3 mm 2 mm 7 mm * * *12 Rif 12 mm 11 mm 16 mm13 Amp 28 mm * * 18 20 30* = No zone of inhibition below 500 μg/mLTable 3: Determination of MICSr. No. CompE. Coli (mm) P. Vulgaris (mm) S. Aureus (mm)450 ppm400 ppm350 ppm300 ppm450 ppm400 ppm350 ppm300 ppm450 ppm400 ppm350 ppm300 ppm1 B5 6 4 1 NR NR NR NR NR 2 NR NR NR2 B8 8 2 NR NR 6 1 NR NR 4 NR NR NR3 B11 NR NR NR NR NR NR NR NR 2 NR NR NR4 Rif 10 7 3 NR 9 5 2 NR 11 8 5 2Determination of insecticidal activity:A study was performed to evaluate insecticidal activity of biscoumarin derivatives against bean weevil Callosobruchus maculatus (F); the most dangerous pest of stored grains. Infected grains of phaseolus were purchased from market and C. maculatus (F) were separated from other species on the basis of morphological difference. These were separately reared in a glass jar containing phaseolus which was covered by muslin cloth and tied with rubber band to provide proper aeration to the culture and used as the stock. After 28-30 days newly hatched adult C. maculatus were observed inside the jar which was used to study the mortality effect of biscoumarins.The grains were initially washed with water and dried in oven at 40-45 oC so as to destroy the infected stages of any pest if exists in grains. Each pre-sterilized glass jar was filled with 10 gm of the grains. Then each compound with 500 μg/mL concentration was applied on grains and left for 48 h to evaporate the solvent. 10 Beetles were allowed to enter inside each jar which was covered with muslin cloth and observed after an interval of 24 h each for 96 h. The rate of mortality was recorded for each compound against C. maculatus (Table 4). The experiment was carried in triplicate and percentage adult mortality was determined by counting the number of dead insects divided by the total number of insects introduced multiplied by 100 [19]. Table 4: Insecticidal activity of biscoumarinsCompoundNumber of insects dead after Total % mortality24 h 48 h 72 h 96 hB1 1 1-2 2 3 75B2 0 1 1 3 50B3 1 2 2 2 70B4 1 1 1 2 50B5 0 1 2 4 70B6 0 0 0 1 10B7 0 0 2 2 40B8 1 1 2 3 70B9 1 1 2 2 60B10 0 1 1 1 30B11 0 2 1 4 70Chemistry & Biology Interface Vol. 8 (1), January – February 201860Chemistry & Biology Interface, 2018, 8, 1, 56-61Figure 4: Plot of total % mortality after 96 hResults and Discussion:In the present work, Yb(OTf)3 was successfully used as a catalyst for the pseudo three-component condensation of aldehyde and 4-hydroxy coumarin in ethanol under reflux condition. Optimization of catalyst concentration for a model reaction of benzaldehyde with 4-hydroxy coumarin showed that only 5 mol% of the catalyst was found to be enough sufficient to catalyze the transformation. Almost all the screened aldehydes including sterically hindered ones reacted under these conditions to afford the corresponding biscoumarin derivatives in good yields.Antibacterial activity of the synthesized biscoumarins revealed that the compound B-8 was active against all the three bacterial strains viz. E. Coli, P. Vulgaris, S. Aureus which showed significant zone of inhibition comparable with that of the standard Rifampicin in case of E. Coli as well as P. Vulgaris but less than in the case of S. Aureus. Biscoumarin B-5 was effective against E. Coli and S. Aureus only and inactive against P. Vulgaris. Compound B-11 was less effective against all the three bacterial strains employed. The remaining biscoumarins were observed to be inactive against the used bacterial strains. The results of minimum inhibitory concentration (MIC) determination for the selected compounds B-5, B-8 and B-11 are mentioned in Table 3. Antifungal activity of the biscoumarins revealed that only the compound B-4 was active against Penicillium fugus and not active against A. Niger and A. Fumigatus at 500 μg/mL concentration. Antifungal activity of the compound B-4 can be attributed to the presence of -NO2 group at meta and F-atom at para position. The remaining compounds were not active against all the three fungi below 500 μg/mL concentration.Compounds B-1, B-3, B-5 and B-11 showed about 70-75% mortality effect on Callosobruchus maculatus whereas B-2, B-4 and B-8 showed 50% of mortality i.e. moderate effect and B-6 showed the least mortality rate to control C. maculatus.Conclusion:In the present study Yb(OTf)3 was used as a catalyst for the synthesis of biscoumarins by pseudo three-component reaction of aldehyde and 4-hydroxycoumarin. The reactions were successful even with sterically hindered aldehydes. Antibacterial activity study revealed that the compounds B-5, B-8 and B-11 possessed moderate to good zones of inhibition against the bacterial strains used. Compound B-4 was found to be active against Penicillium fungus but inactive against Aspergillus niger and Aspergillus fumigatus fungal species. Compounds B-1, B-3 and B-5 showed good mortality rates against C. maculatus (70-75% mortality) after 96 h.Acknowledgements: Authors are thankful to the Principal, Deogiri College, Aurangabad (MS) India for providing the necessary laboratory facilities and to the Director, Sophisticated Analytical Instrumentation Facility, Punjab University, Chandigarh for providing the spectral data. References: Chemistry & Biology Interface Vol. 8 (1), January – February 201861Chemistry & Biology Interface, 2018, 8, 1, 56-611. F.G. Medina, J.G. Marrero, M. Macias-Alonso, M.C. Gonzalez,  I.C. Guerrero, A.G.T. Garcia, S. O. Robles  Nat. Prod. Rep. 2015, 32, 1472-1507. 2. J. C. Jung, Oee-Sook Park Molecules 2009, 14, 4790-4803.3. D. Wardrop, D. Keeling Br J Haematol. 2008, 141(6), 757-63. 4. R. Wallin Biochem J. 1986, 236(3), 685-693.5. J.C. Jung, H.I. Moon. Pharm Biol. 2011, 49(2), 190-193. 6. H.L.T. Anh, D.C. Kim, W. Ko, T.M. Ha, N.X. Nhiem,  P.H. Yen, B.H. Tai, L.H. Truong,  V.N. Long,  T. Gioi, Q.T. Hong,  C.V. Minh, H. Oh,  Y.C. Kim, P.V. Kiem Pharm. Biol. 2017, 55(1), 1195-1201. 7. N. Au,  A.E. Rettie Drug Metab Rev. 2008, 40(2), 355-75.8. J. Lowenthal, H. Birnbaum Science. 1969, 164(3876), 181-183.9. A. Mollica, S. Genovese, F. Pinnen, A. Stefanucci, M. Curini, F. Epifano Tetrahedron  Lett. 2012, 53(7), 890-892. 10. L-M. Wang, J. Sheng, L. Zhang, J-W. Han, Z-Y. Fan, H. Tian, C-T. Qian Tetrahedron  2005, 61(6), 1539-1543.11. A. Kumar, I. Ahmad, M.S. Rao J. Sulfur Chem. 2009, 30(6), 570-577.12. A. Kawada, S. Mitamura, S. Kobayashi  J. Chem. Soc. Chem. Comm.1993, 1157-1158.13. Y. Heo, D.H. Cho, M.K. Mishra, D.O. Jang Tetrahedron Lett. 2012, 53(30), 3897-3899.14. R. Annunziata, Mauro Cinquini, F. Cozzi, V. Molteni, O. Schupp J. Org. Chem. 1996, 61 (23), 8293-8296. 15. F. Epifano, S. Genovese, M. Curini Tetrahedron Lett. 2007, 48(15), 2717-2720. 16. W. Su, D. Yang, C. Jin, B. Zhang Tetrahedron Lett. 2008, 49(21), 3391-3394.17. P.R. Murray, E.J. Baron, M.A. Pfaller, F.C. Tenover, H.R. Yolken Manual Clini. Microbio 6th Ed. ASM Press, D.C. Washington 1995, 15-18. 18. C.H. Collins, P.M. Lyne, J.M.  Grange Microbio. Methods 1995, 7th Ed.  175 - 190.19. L. Lajide, P. Escoubas, J. Mizutani. Phytochem. 1995, 40, 1105-1112.

Yb(OTf)3 Catalyzed Synthesis, Antimicrobial and Insecticidal activity of some Biscoumarins

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Yb(OTf)3 Catalyzed Synthesis, Antimicrobial and Insecticidal activity of some Biscoumarins

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