Malaysian Journal of Analytical Sciences Vol 19 No 2 (2015): 359 – 368

 

 

 

CHEMICAL EXPLORATION OF

4-HYDROXYBENZYLATED 3-SUBSTITUTED TETRAMIC ACID

 

(Penerokaan Kimia bagi 4-Hidroksibenzil 3-Gantian Asid Tetramik)

 

Norhanim Mohalid¹, Ahmad Sazali Hamzah², Zurina Shaameri^2*

 

¹Faculty of Applied Sciences,

²Organic Synthesis Laboratory, Institute of Science,

Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia

 

*Corresponding author: zurina@salam.uitm.edu.my

 

 

Received: 26 February 2014; Accepted: 27 January 2015

 

 

Abstract

The tetramic acid (pyrrolidine-2,4-dione) ring system was discovered as a key structural unit in many natural products. The tetramic acid moiety, in most cases, is present as a 3-acyl derivative. Fuligorubin A, a yellow pigment produced from Fuligo septica, consists of a hydroxybenzyl substituent at the C-5 position of the tetramic acid ring has been reported to show antibiotic and cytotoxic activities. In this project, a derivative of Fuligorubin A, namely 4-hydroxybenzylated 3-acyl tetramic acid from slime mold Leocarpus fragilis is chosen as the synthetic target not only due to the strong biological activity of Fuligorubin A, but mainly due to the challenging structure of the hydroxybenzylated tetramic acid moiety. We are also interested in synthesizing 3,4-fused ring (bicyclic) compounds because they might have comparable medicinal properties with the bioactive compounds, and tetramic acid is the key structural unit. Such fused ring system could be the lead synthon towards the synthesis of lactacystin derivatives. In the development towards the synthesis of the target compounds, our research group has attempted to synthesize them using L-tyrosine as the starting material. All synthesized compounds were characterized using Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FTIR) spectroscopy.

 

Keywords: pyrrolidine-2,4-dione, tetramic acid, acyltetramic acid, fused ring, bicyclic

 

Abstrak

Sistem cecincin asid tetramik (pirolidin-2,4-dion) telah ditemui sebagai unit struktur utama dalam kebanyakan hasilan semulajadi. Pada bahagian asid tetramik, dalam kebanyakan kes, hadir sebagai terbitan 3-asil. Fuligorubin A, pigment kuning yang dihasilkan dari Fuligo septica, mengandungi gantian hidroksibenzil di kedudukan C-5 pada cecincin asid tetramik telah dilaporkan menunjukkan aktiviti antibiotik dan sitotoksik. Dalam projek ini, satu terbitan dari Fuligorubin A, yang dinamakan 4-hidroksibenzil 3-asil asid tetramik dari lendir kulat Leocarpus fragilis telah dipilih sebagai sasaran sintesis bukan sahaja disebabkan aktiviti biologi Fuligorubin A yang kuat, tetapi terutamanya disebabkan oleh struktur hidroksibenzil pada bahagian asid tetramik yang mencabar. Kami juga berminat untuk menghasilkan sebatian 3,4-cecincin bersatu (bisiklik) kerana ia mungkin mempunyai ciri-ciri perubatan yang sama dengan sebatian bioaktif, dan asid tetramik adalah unit struktur utamanya. Sistem cecincin bersatu tersebut boleh menjadi sinton utama terhadap penghasilan terbitan lactacystin. Dalam perkembangan terhadap penghasilan sebatian sasaran, kumpulan penyelidikan kami telah mencuba untuk menghasilkannya menggunakan L-tirosina sebagai bahan permulaan. Kesemua sebatian yang dihasilkan telah dicirikan menggunakan spektroskopik Nuclear Magnetic Resonance (NMR) dan Fourier Transform Infrared (FTIR).

 

Kata kunci: pirolidin-2,4-dion, asid tetramik, asid asiltetramik, gabungan cecincin, bisiklik

 

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