Malaysian Journal of Analytical Sciences Vol 26 No 4 (2022): 755 - 765

 

 

 

 

SYNTHETIC APPROACHES TOWARDS QUINOLACTACIN DERIVATIVES VIA DIELS-ALDER, ACYL MIGRATION AND MULTICOMPONENT REACTIONS

 

(Pendekatan Sintesis Ke Arah Terbitan Quinolaktasin Melalui Tindak Balas Diels-Alder, Migrasi Asil dan Tindak Balas Pelbagai Komponen)

 

Ahmad Zahir Hafiz Ismail1,2, Putri Nur Arina Mohd Arif 1,2, Nurul Syafiqah Rezali3, Mohd Fazli Mohammat2, Zurina Shaameri2*

 

1Organic Synthesis Laboratory, Institute of Science,

Universiti Teknologi MARA Puncak Alam, 43200 Bandar Puncak Alam, Selangor, Malaysia

2Faculty of Applied Sciences,

Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia

3Chemical Sciences Programme,

School of Distance Education, Universiti Sains Malaysia, 11800 Penang, Malaysia

 

*Corresponding author:  zurina@uitm.edu.my

 

 

Received: 18 September 2021; Accepted: 27 February 2022; Published:  25 August 2022

 

 

Abstract

Quinolactacins are rare fungal alkaloids extracted from the culture broth of Penicillium species isolated from larvae mulberry pyralis (Margonia pyloalis Welker). The synthesis of the natural alkaloids has gained interests among many researchers due to its unique 𝛾-lactam conjugated ring quinolone skeleton. Furthermore, the alkaloids are also proven to exhibited inhibitory activities against tumour necrosis factor (TNF) production. Synthesizing the alkaloids is initiated by forming the key pyrrolidine-2,4-dione intermediates via the acid-mediated  Meldrum reaction and tetramic acid cyclisation of different amino acids. Subsequently, the diketo intermediates are reduced and eliminated  to form hydroxy and enone analogues. The enone analogues are then reacted with an amine-substituted diene by aza Diels-Alder reaction to form the anticipated 4-pyridone-lactam moiety with different substitutions. Nonetheless, the availability of amine-substituted dienes is limited even though aza Diels-Alder reactions shorten the formation of the tricyclic compounds. Consequently, the present study synthesised quinolactacin derivatives through alternative routes, including acylating the key pyrrolidine-2,4-dione with 2-nitrobenzoyl chloride to obtain an acylated tetramic acid and hydrogenated and furnish the final quinolactacin derivatives. The derivatives were also procured through a multicomponent reaction of diethyl oxaloacetate salt with aldehydes and amines. The synthesised compounds were analysed and confirmed with proton and carbon nuclear magnetic resonance (1H- and 13C-NMR) and infrared (IR) spectroscopy.

 

Keywords:  Penicillium sp., Diels-Alder, 2,4-pyrrolidinone, quinolactacin

 

Abstrak

Quinolaktasin adalah kulat alkaloid nadir yang terhasil daripada kultur kaldu Penicillium spesies, di ekstrak daripada larva piralis mulberi (Marfonia pyloalis Welker). Sintesis bahan alkaloid yang natural ini telah menarik minat ramai ahli penyelidik oleh kerana keunikan struktur quinolone di mana ianya konjugat bersama gegelang 𝛾-lactam. Alkaloid ini telah dibuktikan bahawa ianya bersikap aktif terhadap aktiviti rencatan melawan penghasilan faktor tumor nekrosis (TNF). Sintesis ini bermula dengan bahantara pirolidina-2,4-dion melalui tindak balas asid Meldrum dan pengitaran asid tetramik dari variasi asid amino. Bahantara diketo pula akan melalui pengurangan berturutan dan tindak balas penyingkiran kumpulan hidroksi dan variasi enon. Variasi enon ini bertindak balas dengan diena amina gantian melalui reaksi aza Diels-Alder bagi menghasilkan sebatian 4-piridona-laktam dengan variasi gantian. Walaupun reaksi kimia aza Diels-Alder dapat membantu menghasilkan sebatian trisiklik dalam langkah yang pendek, tetapi variasi diena amina gentian juga adalah terhad. Oleh itu, sintesis bagi penghasilan variasi quinolaktasin dijalankan melalui cara alternatif di mana pirolidina-2,4-dion menjalani pengasilan dengan 2-nitrobenzoil klorida untuk menghasilkan tetramik asid terasilasi dan penghidrogenan bagi menghasilkan sebatian akhir quinolaktasin. Reaksi pelbagai komponen oleh garam dietil oxaloasetat bersama aldehid dan amina pula adalah alternatif lain bagi penghasilan variasi sebatian quinolaktasin. Semua sebatian di dalam kajian ini dianalisa dan disahkan menggunakan resonans magnet nucleus (1H- dan 13C-NMR) dan spektroskopi infra merah (IR).

 

Kata kunci:  Penicillium sp., diels-alder, 2,4-pirolidina, quinolaktasin

 

 


Graphical Abstract

 

 

References

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