Synthesis of Ethyl 2-(4-halobenzyl)-3-oxobutanoate and determination of its Biological activity by using prediction of activity spectra for substance

Kavita R. Chandramore1, Rohan S. Ahire2

1Department of Pharmaceutical Chemistry, Dr. J. D Pawar College of Pharmacy, Kalwan, Nashik, Maharashtra.

2Department of Pharmaceutical Chemistry, MET’s Institute of Pharmacy, Adgaon, Nashik, Maharashtra.

*Corresponding Author E-mail: [e-mail]

ABSTRACT:

In this study, Synthesis of ethyl 2-(4-halobenzyl)-3-oxobutanoate was carried out by using addition of substituted benzyl bromide to a suspension of t-BuOK (Potassium tert-butoxide) in THF (tetrahydrofuran). The reaction mixture was then refluxed for 12 hr. The progress of reaction was monitored using thin layer chromatography (TLC). Synthesize compound are characterized by elemental analysis and spectral analysis like infra red spectroscopy, nuclear magnetic spectroscopy and mass spectroscopy (IR,1H-NMR, MS). Pharmacological activity of these compound were predicted by individually using prediction of activity spectra for substance (PASS). It shows various pharmacological activities and mechanism of action such as L-glucuronate reductase inhibitor, Gluconate 2-dehydrogenase (acceptor) inhibitor, Centromere associated protein inhibitor, Eye irritation, inactive, GST A substrate, Pectate lyase inhibitor, 5-O-(4-coumaroyl)-D-quinate 3'-monooxygenase inhibitor, Acetylcholine neuromuscular blocking agent, Antihypoxic, Aspulvinone dimethylallyl transferase inhibitor.

KEYWORDS: Substituted benzyl bromide; PASS, Probable activity, Probable Inactivity, Pharmacological activity.

INTRODUCTION:

Synthesis of ethyl 2-(4-halobenzyl)-3-oxobutanoate was carried out (figure 1) by using addition of substituted benzyl bromide to a suspension of t-BuOK in THF1. Two substituted benzyl bromide was used i.e bromo benzyl bromide and chloro benzyl bromide. This reaction is a type of nucleophilic substitution. The three different ethyl 2-(4-substituted benzyl)-3-oxobutanoate compound was synthesize. All the synthesized compounds are listed in Table 1 and their structures are determined by elemental analyses and spectral data (IR, 1 H-NMR, EI-MS) and its pharmacological activity was determine by using prediction of activity spectra for substance (PASS) shown in table 2 and 32,3.

PASS Server, this server predicted activity spectrum of a chemical compound as a Pa (probable activity) and Pi (probable inactivity)4. If Pa ˃ 0.7, the substance is very likely to exhibit the activity in experiment, but the chance of substance being the analogue of known pharmaceutical agent is high. If 0.5 < Pa
MATERIAL AND METHOD:

Material: All starting materials and reagents for the synthesis were purchased from commercial sources. Distilled solvents were used for carrying out reactions as well as column chromatography. All the reactions as well as chromatographic processes were monitored by TLC technique on precoated silica...