Chiral Liquid Chromatography in Analysis of the Stereochemistry of Marine Natural Compounds: Contribution for Medicinal Chemistry

In Medicinal Chemistry many naturally occurring peptides have been used as pharmaceuticals or as models for drugs used in therapeutics. Thus, marine-derived peptides are certainly an interesting source for new drugs. Taking into account the mechanisms of molecular recognition and the influence of molecular three-dimensionality in this process, it is essential to define the amino acids components of the peptide fractions isolated from marine sources.

Chiral liquid chromatography (LC) it has become a very helpful and highly applicable method for preparative resolution of racemates [1], determination of the enantiomeric purity [2], monitoring enantiomeric reactions [3], analysis of the stereochemistry of natural compounds [4, 5], among other applications.

Herein, we describe the determination of the stereochemistry of the amino acid residues of three bioactive marine natural products [4, 5], by chiral LC analysis of their acidic hydrolysates, using appropriate D and L amino acids standards. The enantioseparations of the amino acids were successfully performed with the Chirobiotic T^TM column under reversed-phase elution conditions. Actually, the teicoplanin selector of this column has several characteristic features that make it suitable for amino acid analysis [6]. The elution order of the enantiomers of all the standards amino acids was confirmed by injecting the solutions of the racemic or enantiomeric mixtures and then each enantiomer separately.

Chiral LC technique demonstrated to be decisive leading to the unambiguous elucidation of the amino acid constituents of the three bioactive marine natural products.

Acknowledgements: This work was partially supported through national funds from Foundation for Science and Technology (FCT) and European Regional Development Fund (ERDF) and COMPETE under the projects UID/Multi/04423/2013, PTDC/MAR-BIO/4694/2014 (POCI-01-0145-FEDER-016790), and INNOVMAR (Innovation and Sustainability in the Management and Exploitation of Marine Resources) - NORTE-01-0145-FEDER-000035, Research Line NOVELMAR. War War May Zin thanks the Lotus Unlimited Project under the ERASMUS MUNDUS ACTION 2-EU-Asia Mobility Project for a Ph.D. scholarship. Chadaporn Prompanya thanks the Faculty of Pharmaceutical Sciences, Burapha University, Thailand for her scholarship to the University of Porto. War War May Zin and Chadaporn Prompanya equally contributed to this work.

[1] M.E. Sousa, M.E. Tiritan, K.R.A. Belaz, M. Pedro, M.S.J. Nascimento, Q.B. Cass, M.M.M. Pinto, J. Chromatogr. A, 1120 (2006) 75-81.

[2] B. Silva, C. Fernandes, M.E. Tiritan, M.M.M. Pinto, M.J. Valente, M. Carvalho, P.G. de Pinho, F. Remião, Forensic Toxicol., (2016) 1-14.

[3] C. Fernandes, P. Brandão, A. Santos, M.E. Tiritan, C. Afonso, Q.B. Cass, M.M. Pinto, J. Chromatogr. A, 1269 (2012) 143-153.

[4] C. Prompanya, C. Fernandes, S. Cravo, M.M.M. Pinto, T. Dethoup, A.M.S. Silva, A. Kijjoa, Mar. Drugs, 13 (2015) 1432-1450.

[5] W.W.M. Zin, S. Buttachon, T. Dethoup, C. Fernandes, S. Cravo, M.M.M. Pinto, L. Gales, J.A. Pereira, A.M.S. Silva, N. Sekeroglu, A. Kijjoa, Mar. Drugs, 14 (2016).

[6] A. Berthod, Y. Liu, C. Bagwill, D.W. Armstrong, J. Chromatogr. A, 731 (1996) 123-137.