*Corresponding Author Address: Dr. Urbain C. Kasséhin, Laboratoire de Chimie Pharmaceutique Organique(MOCL), Ecole de Pharmacie, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Campus du Champ de Foire, 01 BP 188, Cotonou, Bénin. World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Original Article Use of natural aminoacids as efficient green catalyst in the synthesis of thiosemicarbazones Urbain C. Kasséhin* 1, 2 , Odilon Q. ASSAN 1 , Fernand A. Gbaguidi 1 , Julien R. C. Prévost, Raphaël Frédérick 2 , and Jacques H. Poupaert 1, 2 1 Laboratoire de Chimie Pharmaceutique Organique(MOCL), Ecole de Pharmacie, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Campus du Champ de Foire, 01 BP 188, Cotonou, Bénin. 2 Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université catholique de Louvain., Av. E. Mounier, 73, Box B1.73.10, B-1200 Bruxelles, Belgium. Received: 23-11-2016 / Revised: 21-12-2016 / Accepted: 28-12-2016 / Published: 01-01-2017 ABSTRACT In an effort to find improved conditions for the synthesis of medicinally relevant thiosemicarbazones basing our approach on green chemistry approach, we used ten natural alpha aminoacids as nucleophilic catalysts.We therefore hypothetized that aminoacid acid being amphoteric reagent, should be able to boost a reaction submitted to general acid-base catalysis. Using cyclohexanone 4-phenylthiosemicarbazone as target compound for our benchmark reaction, we were able to demonstrate the validity of our hypothesis. A plot of “hydrophobicity/lipophilicity” balance as reflected by logP and the net actual yield does not show any significant correlation, however it is remarkable to note that while L-phenylalanine shows opposite behavior in water (94%) and methanol (24%), glycine – the most concise alpha-amino-acid – performs equally very well in both solvents (95% and 90%, respectively). These green catalysts and specially glycine may be useful in the elaboration of a compound library. Keywords: Natural alpha-aminoacids - Green efficient catalyst- Nucleophilic catalysis-Thiosemicarbazones INTRODUCTION Many enzymes behave as exceptional asymmetric catalysts, performing reactions very effectively and often very selectively [1-4]. In an effort to imitate enzymatic efficiencies, chemists have dived into the natural chiral tool, transforming amino acids into numerous chiral auxiliaries, catalysts, and ligands. In most representative examples, the alpha-amino acid is used purely as a source of chirality and both the amine and acid functionality are altered or even eliminated [5-6].Unmodified amino acids and peptides have been used as catalysts by far much less frequently [7]. Hajos and Wiechert reported the use of proline as a catalyst for the Robinson annellation as early as 1970 [8-9].Wiechert and co-workers indeed at Schering AG reported direct conversion to the target enone. A catalytic quantity of (S)-proline(3 mol%) was sufficient to mediate the aldol cyclization yielding the bicyclic ketol in virtually 100% yield along with a 93% enantiomeric excess. The idea that a short peptide or even a single amino-acid would be able to function as a pared- down version of an enzyme was first generally met with considerable skepticism in the community of synthetic organic chemists. However, behind enzymatic tactics one can count nucleophilic catalysis, which has been implemented already in the 1960’s with great success by Jencks et al. [10- 12], using rather common laboratory reagents as simple as anilinium chloride. When this approach is employed in conjunction with anchimeric assistance, such as that provided by the potent alpha-effect, a miniaturized version of a molecular motoris produced, which is able to boost a plethora of elementary reactions including the synthesis of thiosemicarbazones, as amply documented by Kassehin et al.[13-14]. A key demonstration of this synergetic action using both nucleophic and anchimeric assistance is delivered by sulfanilic acid or anthranilic acid, for instances. Along this line, we recently became interested in using such an approach using water as solvent [15-16]. This