Novel Piperidine and 3,4-dihydro-2H-pyrrole Alkaloids from Tilia platyphyllos and Tilia cordata Flowers

 

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Abstract

Lime flowers, traditionally used for medical purposes for the treatment of symptoms of the common cold and mental stress, consist of the dried inflorescences including the floral bracts of Tilia cordata, Tilia platyphyllos, Tilia × vulgaris, or mixtures thereof. During phytochemical investigations, 6 different alkaloids – not described until now – were detected in T. cordata and T. platyphyllos flowers. They have been isolated and characterized as alkaloids with a dihydro-pyrrole and a piperidine substructure, respectively. Compounds 1a and 1b (tiliines A and B) are characterized as 2 diastereomers containing a 2-methyl-3,4-dihydro-2H-pyrrol-3-ol, connected via a C-10 alkyl chain to a O-glucosylated hydroquinone moiety. Compounds 2a and 2b (tiliamines A and B) are diastereomers of a 2-methyl-substituted piperidin-3-ol, coupled via a C-9 alkyl chain again to an O-glucosylated hydroquinone moiety. Compounds 3a and 3b (tilacetines A and B) are 3-O-acetylated derivatives of tiliamines. Quantification of the 6 alkaloids by HPLC-ESI-qTOF analysis indicated the presence of all alkaloids in T. cordata flowers and T. platyphyllos flowers, bracts, and leaves, with tiliines A and B and tilacetines A and B being the major compounds. Acetone/water turned out be the best extraction solvent for the alkaloids, but ethanol and ethanol/water mixtures also can be used for effective extraction. Furthermore, the alkaloids are found in hot water extracts, which are typically used in the traditional medicine.

Publication History

Received: 26 October 2020

Accepted after revision: 15 December 2020

Article published online:
12 January 2021

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• References

• 1 Committee on Herbal Medicinal Products. HMPC monograph Tiliae flos–Community herbal monograph on Tilia cordata Miller, Tilia platyphyllos Scop., Tilia × vulgaris Heyne or their mixtures, flos. EMA/HMPC/337066/2011. Accessed August 6, 2020 at: https://www.ema.europa.eu/en/medicines/herbal/tiliae-flos
  Google Scholar
• 2 Committee on Herbal Medicinal Products. HMPC assessment report Tiliae flos–Assessment report on Tilia cordata Miller, Tilia platyphyllos Scop., Tilia × vulgaris Heyne or their mixtures, flos. EMA/HMPC/337067/2011. Accessed August 6, 2020 at: https://www.ema.europa.eu/en/medicines/herbal/tiliae-flos
  Google Scholar
• 3 Council of Europe–European Directorate for the Quality of Medicines. European Pharmacopoiea 10.0: Lime Flower–Tiliae flos. Stuttgart, Germany: Deutscher Apotheker Verlag; 2020
  Google Scholar
• 4 Karioti A, Chiarabini L, Alachkar A, Fawaz Chehna M, Vincieri FF, Bilia AR. HPLC-DAD and HPLC-ESI-MS analyses of Tiliae flos and its preparations. J Pharm Biomed Anal 2014; 100: 205-214 doi:10.1016/j.jpba.2014.08.010
  CrossrefPubMedGoogle Scholar
• 5 Negri G, Santi D, Tabach R. Flavonol glycosides found in hydroethanolic extracts from Tilia cordata, a species utilized as anxiolytics. Rev Bras Plantas Med 2013; 15: 217-224 doi:10.1590/S1516-05722013000200008
  CrossrefPubMedGoogle Scholar
• 6 Toker G, Aslan M, Yeşilada E, Memişoğlu M, Ito S. Comparative evaluation of the flavonoid content in officinal Tiliae flos and Turkish lime species for quality assessment. J Pharm Biomed Anal 2001; 26: 111-121 doi:10.1016/s0731-7085(01)00351-x
  CrossrefPubMedGoogle Scholar
• 7 Kram G, Franz G. Untersuchungen über die Schleimpolysaccharide aus Lindenblüten. Planta Med 1983; 49: 149-153 doi:10.1055/s-2007-969836
  Article in Thieme ConnectPubMedGoogle Scholar
• 8 Toker G, Baser KHC, Kürkçüoglu M, Özek T. The composition of essential oils from Tilia L. Species Growing in Turkey. J Essent Oil Res 1999; 11: 369-374 doi:10.1080/10412905.1999.9701158
  CrossrefPubMedGoogle Scholar
• 9 Symma N, Sendker J, Petereit F, Hensel A. Multistep analysis of Diol-LC-ESI-HRMS data reveals proanthocyanidin composition of complex plant extracts (PAComics). J Agric Food Chem 2020; 68: 8040-8049 doi:10.1021/acs.jafc.0c02826
  CrossrefPubMedGoogle Scholar
• 10 Schmidgall J, Schnetz E, Hensel A. Evidence for bioadhesive effects of polysaccharides and polysaccharide-containing herbs in an ex vivo bioadhesion assay on buccal membranes. Planta Med 2000; 66: 48-53 doi:10.1055/s-2000-11118
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Buchbauer G, Jirovetz L, Jäger W. Passiflora and lime-blossoms: motility effects after inhalation of the essential oils and of some of the main constituents in animal experiment. Arch Pharm 1992; 325: 247-248 doi:10.1002/ardp.19923250410
  CrossrefPubMedGoogle Scholar
• 12 Still PC, Yi B, González-Cestari TF, Pan L, Pavlovicz RE, Chai HB, Ninh TN, Li C, Soejarto DD, McKay DB, Kinghorn AD. Alkaloids from Microcos paniculata with cytotoxic and nicotinic receptor antagonistic activities. J Nat Prod 2013; 76: 243-249 doi:10.1021/np3007414
  CrossrefPubMedGoogle Scholar
• 13 Chaves OS, Gomes RA, Tomaz AC, Fernandes MG, das Graças Mendes L, de Fátima Agra M, Braga VA, de Fátima Vanderlei Souza M. Secondary metabolites from Sida rhombifolia L. (Malvaceae) and the vasorelaxant activity of cryptolepinone. Molecules 2013; 18: 2769-2777 doi:10.3390/molecules18032769
  CrossrefPubMedGoogle Scholar
• 14 Chaves OS, Teles YC, Monteiro MM, Mendes Junior LG, Agra MF, Braga VA, Silva TM, Souza MF. Alkaloids and phenolic compounds from Sida rhombifolia L. (Malvaceae) and vasorelaxant activity of two indoquinoline alkaloids. Molecules 2017; 22 DOI: 10.3390/molecules22010094.
  CrossrefPubMedGoogle Scholar
• 15 Noe CR, Freissmuth J. Capillary zone electrophoresis of aldose enantiomers: separation after derivatization with S-(−)-1-phenylethylamine. J Chromatogr A 1995; 704: 503-512 doi:10.1016/0021-9673(95)00237-H
  CrossrefPubMedGoogle Scholar
• 16 Periyannan GR, Lawrence BA, Egan AE. ¹H NMR spectroscopy-based configurational analysis of mono- and disaccharides and detection of β-glucosidase activity: an undergraduate biochemistry laboratory. J Chem Educ 2015; 92: 1244-1249 doi:10.1021/ed500578c
  CrossrefPubMedGoogle Scholar
• 17 Melhaoui A, Bodo B. Irnigaine and N-Methylirnigaine, two new piperidinol alkaloids from the tubers of Arisarum vulgare . Nat Prod Let 1995; 7: 101-108 doi:10.1080/10575639508043196
  CrossrefPubMedGoogle Scholar
• 18 Su Y, Xu JJ, Bi JL, Wang YH, Hu GW, Yang J, Yin GF, Long CL. Chemical constituents of Arisaema franchetianum tubers. J Asian Nat Prod Res 2013; 15: 71-77 doi:10.1080/10286020.2012.723202
  CrossrefPubMedGoogle Scholar
• 19 Huang W, Yi X, Feng J, Wang Y, He X. Piperidine alkaloids from Alocasia macrorrhiza . Phytochem 2017; 143: 81-86 doi:10.1016/j.phytochem.2017.07.012
  CrossrefPubMedGoogle Scholar
• 20 Freitas TR, Danuello A, Viegas Júnior C, Bolzani VS, Pivatto M. Mass spectrometry for characterization of homologous piperidine alkaloids and their activity as acetylcholinesterase inhibitors. Rapid Commun Mass Sp 2018; 32: 1303-1310 doi:10.1002/rcm.8172
  CrossrefPubMedGoogle Scholar
• 21 Bolzani VS, Leslie Gunatilaka AA, Kingston DGI. Bioactive and other piperidine alkaloids from Cassia leptophylla . Tetrahedron 1995; 51: 5929-5934 doi:10.1016/0040-4020(95)00254-6
  CrossrefPubMedGoogle Scholar
• 22 Christofidis I, Welter A, Jadot J. Spectaline and iso-6 cassine, two new piperidin 3-ol alkaloids from the leaves of Cassia spectabilis . Tetrahedron 1977; 33: 977-979 doi:10.1016/0040-4020(77)80211-1
  CrossrefPubMedGoogle Scholar
• 23 Christofidis I, Welter A, Jadot J. Spectalinine and iso-6-carnavaline, two unprecedented piperidine alkaloids from the seeds of Cassia spectabilis . Tetrahedron 1977; 33: 3005-3006 doi:10.1016/0040-4020(77)88038-1
  CrossrefPubMedGoogle Scholar
• 24 Luis AS, Karin JS, Schmeda-Hirschmann G, Griffith GA, Holt DJ, Jenkins PR. DNA binding alkaloids from Prosopis alba . Planta Med 1999; 65: 161-162 doi:10.1055/s-2006-960454
  Article in Thieme ConnectPubMedGoogle Scholar
• 25 Reina L, Bennadji Z, Vinciguerra V, Ferreira F, Moyna G, Menendez P. Isolation and structural characterization of new piperidine alkaloids from Prosopis affinis . Phytochem Lett 2015; 14: 265-269 doi:10.1016/j.phytol.2015.10.022
  CrossrefPubMedGoogle Scholar
• 26 Feng SX, Lin LD, Xu HH, Wei XY. Two new piperidine alkaloids from the leaves of Microcos paniculata . J Asian Nat Prod Res 2008; 10: 1155-1158 doi:10.1080/10286020802361289
  CrossrefPubMedGoogle Scholar
• 27 Zhang G, Zhang N, Xu L, Wu HT, Chen D, Lin QH, Luo LZ. A new piperidine alkaloid from the leaves of Microcos paniculata L. Nat Prod Res 2017; 31: 169-174 doi:10.1080/14786419.2016.1224868
  CrossrefPubMedGoogle Scholar
• 28 Bandara KA, Kumar V, Jacobsson U, Molleyres LP. Insecticidal piperidine alkaloid from Microcos paniculata stem bark. Phytochem 2000; 54: 29-32 doi:10.1016/S0031-9422(00)00025-X
  CrossrefPubMedGoogle Scholar
• 29 Aguinaldo AM, Read RW. A major piperidine alkaloid from Microcos philippinensis . Phytochem 1990; 29: 2309-2313 doi:10.1016/0031-9422(90)83058-9
  CrossrefPubMedGoogle Scholar
• 30 Lindquist N, Shigematsu N, Pannell L. Corydendramines A and B, defensive natural products of the marine hydroid Corydendrium parasiticum . J Nat Prod 2000; 63: 1290-1291 doi:10.1021/np000050h
  CrossrefPubMedGoogle Scholar
• 31 Albersheim P, Nevins DJ, English PD, Karr A. A method for the analysis of sugars in plant cell-wall polysaccharides by gas-liquid chromatography. Carbohydr Res 1967; 5: 340-345 doi:10.1016/S0008-6215(00)80510-8
  CrossrefPubMedGoogle Scholar

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