Tautomerism in Flindersine - A DFT Treatment

  • Lemi Türker Department of Chemistry, Middle East Technical University, Üniversiteler, Eskişehir Yolu No: 1, 06800 Çankaya/Ankara, Turkey
Keywords: flindersine, tautomerism, valance tautomerism, transition state, density functional


Flindersine is a natural product of plant kingdom. Its structure contains a lactam group which could undergo 1,3-type proton tautomerism. It also has an embedded pyran moiety which might show valence tautomerism. Presently, those tautomers are investigated within the restrictions of density functional theory at the level of B3LYP/6-311++G(d,p). Certain quantum chemical output has been collected compared and discussed. Also the possibility of valence tautomerism has been searched by proposing two transition state paths.


H. Matthes and E. Schreiber, Flindersine from wood of Flindersia australis R.Br., Rutaceae, Ber. Dtsch. Pharm. Ges. 24 (1914), 385-444.

R. F. C. Brown, J. J. Hobbs, G. K. Hughes and E. Ritchie, The chemical constituents of Australian Flindersia species. VI. The structure and chemistry of Flindersine, Aust. J. Chem. 7 (1954), 348-377. https://doi.org/10.1071/CH9540348

R. F. C. Brown, G. K. Hughes and E. Ritchie, The chemical constituents of Australian Flindersia species. IX. A synthesis of Flindersine, Aust. J. Chem. 9 (1956), 277-282. https://doi.org/10.1071/CH9560277

R. F. C. Brown, The chemical constituents of Australian Flindersia Species. VII. The synthesis of derivatives of kokusagininic and skimmianinic acids, Aust. J. Chem. 8(1) (1955), 121-124. https://doi.org/10.1071/CH9550121

V. Duraipandiyan and S. Ignacimuthu, Antibacterial and antifungal activity of Flindersine isolated from the traditional medicinal plant, Toddalia asiatica (L.) Lam, J. Ethnopharmacol. 123(3) (2009), 494-498. https://doi.org/10.1016/j.jep.2009.02.020

S. Ahmad, Flindersine from Fagara heitzii, J. Nat. Prod. 47(2) (1984), 391-392. https://doi.org/10.1021/np50032a035

V. Duraipandiyan, K. Baskar, C. Muthu, S. Ignacimuthu and N. A. Al-Dhabi, Bioefficacy of flindersine against Helicoverpa armigera Hübner, Spodoptera litura Fabricius, Anopheles stephensis Liston. and Culex quinquefasciatus Say, Braz. Arch. Biol. Technol. 58(4) (2015), 595-604. https://doi.org/10.1590/S1516-8913201500282

F. O’Donnell, T. J. P. Smyth, V. N. Ramachandran and W. F. Smyth, A study of the antimicrobial activity of selected synthetic and naturally occurring quinolines, Int. J. Antimicrob. Agents 35(1) (2009), 30-38. https://doi.org/10.1016/j.ijantimicag.2009.06.031

A. Thawabteh, S. Juma, M. Bader, D. Karaman, L. Scrano, S. A. Bufo and R. Karaman, The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens, Toxins 11(11) (2019), 656-684. https://doi.org/10.3390/toxins11110656

K. C. Majumdar and P. K. Choudhury, Regioselective synthesis of flindersine analogues, Synth. Commun. 23(8) (1993), 1087-1100. https://doi.org/10.1080/00397919308018586

R. M. Bowman, M. F. Grundon and K. J. James, Quinoline alkaloids. Part XVI. 2,2-Dimethylpyranoquinolines from base-catalysed rearrangement of isoprenyl epoxides. Synthesis and biogenesis of flindersine, J. Chem. Soc., Perkin Trans. 1 (1973), 1055-1059. https://doi.org/10.1039/p19730001055

M. Ramesh, P. S. Mohan and P. Shanmugam, A convenient synthesis of flindersine, atanine and their analogues, Tetrahedron 40(20) (1984), 4041-4049. https://doi.org/10.1016/0040-4020(84)85084-x

Y. R. Lee, H. I. Kweon, W. S. Koh, K. R. Min, Y. Kim and S. H. Lee, One-pot preparation of pyranoquinolinones by ytterbium(iii) trifluoromethanesulfonate-catalyzed reactions: Efficient synthesis of flindersine, N-methylflindersine, and zanthosimuline natural products, Synthesis 12 (2001), 1851-1855. https://doi.org/10.1055/s-2001-17516

P. Gunasekaran, P. Prasanna, S. Perumal and A. I. Almansour, ZnCl2-catalyzed three-component domino reactions for the synthesis of pyrano[3,2-c]quinolin-5(6H)-ones, Tetrahedron Lett. 54(25) (2013), 3248-3252. https://doi.org/10.1016/j.tetlet.2013.04.022

P. L. Gentili, F. Ortica, A. Romani and G. Favaro, Effects of proximity on the relaxation dynamics of flindersine and 6(5H)-phenanthridinone, J. Phys. Chem. A 111(2) (2007), 193-200. https://doi.org/10.1021/jp0646426

A. de Groot and B. J. M. Jansen, A simple synthesis of 2h-pyrans; a one-step synthesis of flindersine, Tetrahedron Lett. 16 (1975), 3407-3410. https://doi.org/10.1016/S0040-4039(00)91410-2

H. Li, Y. Tang and R. P. Hsung, Investigating thermal dimerization of N-methyl-flindersine. Syntheses and characterizations of paraensidimerines, Tetrahedron Lett. 53(45) (2012), 6138-6143. https://doi.org/10.1016/j.tetlet.2012.08.147

J. J. P. Stewart, Optimization of parameters for semiempirical methods I. Method, J. Comput. Chem. 10 (1989), 209-220. https://doi.org/10.1002/jcc.540100208

J. J. P. Stewart, Optimization of parameters for semiempirical methods II. Applications, J. Comput. Chem. 10 (1989), 221-264. https://doi.org/10.1002/jcc.540100209

A. R. Leach, Molecular Modeling, Essex: Longman, 1997.

P. Fletcher, Practical Methods of Optimization, New York: Wiley, 1990.

W. Kohn and L. Sham, Self-consistent equations including exchange and correlation Effects, Phys. Rev. 140 (1965), 1133-1138. https://doi.org/10.1103/PhysRev.140.A1133

R. G. Parr and W. Yang, Density Functional Theory of Atoms and Molecules, London: Oxford University Press, 1989.

C. J. Cramer, Essentials of Computational Chemistry, Chichester, West Sussex: Wiley, 2004.

A. D. Becke, Density-functional exchange-energy approximation with correct asymptotic behavior, Phys. Rev. A 38 (1988), 3098-3100. https://doi.org/10.1103/PhysRevA.38.3098

S. H. Vosko, L. Wilk and M. Nusair, Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis, Can. J. Phys. 58 (1980), 1200-1211. https://doi.org/10.1139/p80-159

C. Lee, W. Yang and R. G. Parr, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Phys. Rev. B 37 (1988), 785-789. https://doi.org/10.1103/PhysRevB.37.785

SPARTAN 06, Wavefunction Inc., Irvine CA, USA, 2006.

O. Reutov, Theoretical Principles of Organic Chemistry, Moscow: Mir Pub, 1970.

E. V. Anslyn and D. A. Dougherty, Modern Physical Organic Chemistry, Sausalito, California: University Science Books, 2006.

S. Sarel and J. Rivlin, Ring-chain valence tautomerism in chlorinated 2h-pyran systems, Tetrahedron Lett. 6(13) (1965), 821-828. https://doi.org/10.1016/S0040-4039(00)90025-X

C. D. Gabbutt, B. M. Heron, S. B. Kolla, C. Kilner, S. J. Coles, P. N. Horton and M. B. Hursthouse, Ring contraction during the 6π-electrocyclisation of naphthopyran valence tautomers, Org. Biomol. Chem. 6(17) (2008), 3096-3104. https://doi.org/10.1039/b807744d

C. M. Moorhoff, New annulation techniques; condensations of phosphonium ylides and substituted 2H-pyran-5-carboxylates; preparation of cyclohexenonedicarboxylates and cyclohexadienedicarboxylates, J. Chin. Chem. Soc. 50 (2003), 419-424. https://doi.org/10.1002/jccs.200300064

L. R. Smith, Schemes and transformations in the (CH)8 series, The “valence isomers” of cyclooctatetraene, J. Chem. Educ. 55(9) (1978), 569-576. https://doi.org/10.1021/ed055p569

D. Tejedor, S. Delgado-Hernández, R. Diana-Rivero, A. Díaz-Díaz and F. García-Tellado, Recent advances in the synthesis of 2H-pyrans, Molecules 24 (2019), 2904-2920. https://doi.org/10.3390/molecules24162904

J. D. Hepworth and B. M. Heron, Synthesis and photochromic properties of naphthopyrans, in: Progress in Heterocyclic Chemistry, G.W. Gribble, J.A. Joule, eds., vol. 17, pp. 33-62, Oxford (UK): Elsevier, 2005. https://doi.org/10.1016/S0959-6380(05)80324-1

E. Vogel, Valence isomerizations in compounds with strained rings, Angew. Chem. Int. Ed. Engl. 2 (1963), 1-11. https://doi.org/10.1002/anie.196300011

E. N. Marvell, G. Caple, T. A. Gosink and G. Zimmer, Valence isomerization of a cis- dienone to an α-pyran, J. Am. Chem. Soc. 88 (1966), 619-620. https://doi.org/10.1021/ja00955a050

E. N. Marvell and T. A. Gosink, Valence isomerization of 2,4,6-trimethyl-2H-pyran, J. Org. Chem. 37 (1972), 3036-3037. https://doi.org/10.1021/jo00984a030

T. A. Gosink, Valence isomers. Substituent effects on the equilibrium between 2H-pyrans and cis dienones, J. Org. Chem. 39 (1974), 1942-1944. https://doi.org/10.1021/jo00927a032

O. V. Drygina, A. D. Garnovskii and A. V. Kazantsev, The interconversions of pyrylium salts, pyrans, pyrones, and their open-chain forms, Russ. Chem. Rev. 54(12) (1985), 1167-1184. https://doi.org/10.1070/rc1985v054n12abeh003163

R. Shakirov, M. V. Telezhenetskaya, I. A. Bessonova, S. F. Aripova, I. A. Israilov, M. N. Sultankhodzhaev, V. I. Vinogradova, V. I. Akhmedzhanova, T. S. Tulyaganov, B. T. Salimov and V. A. Tel’nov, Alkaloids. plants, structures, properties, Chem. Nat. Compd. 32 (1996), 932-1028. https://doi.org/10.1007/BF01374041

How to Cite
Türker, L. (2020). Tautomerism in Flindersine - A DFT Treatment. Earthline Journal of Chemical Sciences, 4(2), 89-104. https://doi.org/10.34198/ejcs.4220.89104