Synthesis and Antibacterial Activities of Citral Derivatives

Citral, a bioactive compound in Palmrose oil, although known to have antibacterial effect, has not been used in current drug research. Optimization of the lead structure could enhance the utility of this compound. Hence citral was modified using natural amino acids to produce the Schiff’s base, a potential pharmacophore and the corresponding amines. In this study, we report the synthesis of 9 Schiff’s bases, and the corresponding amines (Reduced product) and their antibacterial activities. Introduction Natural Products were the basis of the first pharmaceutical Practice and they continue to play an important role in modern chemotherapy. They are the most successful source of drug leads. The global scenario is now changing towards the use of these non-toxic plant products having traditional medicinal use emphasizing the development of modern drugs from natural sources for the control of various deceases. Although herbal medicines in form of crude extracts have been used from time immemorial, modern drugs can be developed after extensive investigation of its bioactivity, mode of action, pharmacotherapecutics, and toxicity and after proper standardization and clinical trials. Citral, or 3,7-dimethyl-2,6-octadienal or lemonal, is either of, or a mixture of, a pair of terpenoids with the molecular C10H16O. The two compounds are double bond isomers. It has strong anti-microbial qualities, and pheromonal effects in insects. Citral seem to be a very good synthon for the development of active molecules. In the present study, an attempt has been made for the synthesis of novel compounds from citral. Citral is the primary component of the essential oil of lemongrass, constituting well over half the total oil content. Citral is one of the many chemicals giving lemongrass its strong lemony aroma, and it is also found in lemons and a number of other lemon-scented herbs. Citral has been studied for its potential to treat cancer, due to its ability to induce cell death (apoptosis) in 230 S. Narasimhan et al cancer cells. Cancer cells are able proliferate in part by deactivating the cell death program, which normally causes damaged or mutated cells to self-destruct. The work on citral inducing cell death in cancer cells comes from in vitro experiments (controlled laboratory experiments, as in test tubes or petri dishes), and these results have not been verified in human or animal studies. It is not known the degree to which these properties would actually carry through into humans drinking lemongrass tea or taking extracts of lemongrass as herbal supplements. In this study, we report the synthesis of 9 Schiff’s bases, and the corresponding amines ( Reduced product) and their antibacterial activities. Materials and Methods Fresh Citral was purchased, and purified by distillation. The purity was confirmed by GC, and NMR. Amino acid esters, solvents were purchased from Sigma-Aldrich and were used as supplied. Thin-layer chromatography (TLC) was performed on 0.25 mm pre coated silica gel 60 F254 aluminum sheets and column chromatography on silica gel 60 (0.063-0.2 mm) as well as silica gel 60 (<0.063 mm), products of Merck & Co. (Darmstadt, Germany). The C & HNMR spectra were recorded, with a Bruker (500 MHz) spectrometer, with TMS as internal standard.CDCl3 was used as the solvent. Experimental The Azomethine was obtained by refluxing citral with corresponding amino acid methyl ester in methanol medium, using triethyl amine as the catalyst. The aminederivative azomethine was also made in the same fashion. Azomethine obtained was further reduced to corresponding amines by treating the with sodium borohydride in methanol medium. The scheme is given below