Synthesis of aminoanthraquinone derivatives from quinizarin

Amino derivatives of anthraquinone have been known to have a wide range of reactivities as anticancer agents, where modifications such as reduction, alkylation, or acylation to the anthraquinones also play important roles to increase their bioactivities. Twelve aminoanthraquinones including eight ne...

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Main Author:	Juhan, Siti Fadilah
Format:	Thesis
Language:	English
Published:	2013
Subjects:	Organic chemistry Anthraquinones
Online Access:	http://psasir.upm.edu.my/id/eprint/67492/1/FS%202013%2087%20IR.pdf
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spelling	my-upm-ir.674922019-03-14T02:35:54Z Synthesis of aminoanthraquinone derivatives from quinizarin 2013-10 Juhan, Siti Fadilah Amino derivatives of anthraquinone have been known to have a wide range of reactivities as anticancer agents, where modifications such as reduction, alkylation, or acylation to the anthraquinones also play important roles to increase their bioactivities. Twelve aminoanthraquinones including eight new aminoanthraquinones were synthesized via two different routes that consisted of two-step reactions. In the first route, quinizarin (6) was subjected to reduction, alkylation and acylation separately, thus giving an intermediate of 4-hydroxyanthracene-1,10-dione (82), 1-hydroxy-4-methoxyanthracenedione (49) and 4-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-yl acetate (84) before further reacting to produce anthracene-1,4-dione (83), 1,4-dimethoxyanthracene-9,10-dione (50) and 9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (85) in excellent yields. These three products were then treated with butyamine (BuNH2) in the presence of iodobenzene-diacetate (PhI(OAc)2) as a catalyst to produce aminoanthraquinones 2-(butylamino)anthracene-1,4-dione (83a), 2-(butylamino)-4-methoxyanthracene-9,10-dione(50a),2,3(dibutylamino)anthracene-9,10-dione (50b), 1-(butylamino)-4-methoxyanthacene-9,10-dione (50c), 1,4-(dibutylamino)anthracene-9,10-dione (50d) and 2-(butylamino)-1,4-dihydroxyanthracene-9,10-dione (86). In the second route, compound 6 first underwent amination to give 2-(butylamino)-1,4-dihydroxyanthracene-9,10-dione (86) (major product) and 1-(butylamino)-4-hydroxyanthracene-9,10-dione (87, minor product). Compound 86 was then subjected to reduction, alkylation and acylation separately. Reduction of compound 86 resulted in the compound 83a which is the same compound produced in the first route whereas methylation gave a mixture of 2-(butyamino)-1-hydroxy 4-methoxyanthracene-9,10-dione (86a) and 2-(butyamino)-1,4-dimethoxyanthracene-9,10-dione (86b). The acylation produced a mixture of 3-(butylamino)-4-hydroxy-9,10-dioxo-9,10 dihydroanthracene-1-yl acetate (86c), 2-(butylamino)-4-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-yl acetate (86d) and 2-(butylamino)-9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (86e). The products were characterised via a variety of physico-chemical and spectroscopic techniques, including melting point measurements, Fourier Transform Infrared Spectroscopy (FT-IR), Direct Injection Mass Spectrometry (DI-MS), Gas Chromatography Mass Spectrometry (GCMS) and also Nuclear Magnetic Resonance spectroscopy (NMR). Compound 86e exhibited strong antimicrobial activities toward Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Candida albicans and Escherichia coli (MIC values of 0.1 - 0.5 mg/mL). Meanwhile, compounds 83a, 50a, 50c, 86a, 86b and 86e showed strong activities against both human estrogen receptor positive breast cancer (MCF-7) (IC50 1.1 - 11.0 μg/mL) and human hepatocarcinoma (Hep-G2) (IC50 1.1 - 14.0 μg/mL) cell lines. Organic chemistry Anthraquinones 2013-10 Thesis http://psasir.upm.edu.my/id/eprint/67492/ http://psasir.upm.edu.my/id/eprint/67492/1/FS%202013%2087%20IR.pdf text en public masters Universiti Putra Malaysia Organic chemistry Anthraquinones
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Organic chemistry Anthraquinones
spellingShingle	Organic chemistry Anthraquinones Juhan, Siti Fadilah Synthesis of aminoanthraquinone derivatives from quinizarin
description	Amino derivatives of anthraquinone have been known to have a wide range of reactivities as anticancer agents, where modifications such as reduction, alkylation, or acylation to the anthraquinones also play important roles to increase their bioactivities. Twelve aminoanthraquinones including eight new aminoanthraquinones were synthesized via two different routes that consisted of two-step reactions. In the first route, quinizarin (6) was subjected to reduction, alkylation and acylation separately, thus giving an intermediate of 4-hydroxyanthracene-1,10-dione (82), 1-hydroxy-4-methoxyanthracenedione (49) and 4-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-yl acetate (84) before further reacting to produce anthracene-1,4-dione (83), 1,4-dimethoxyanthracene-9,10-dione (50) and 9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (85) in excellent yields. These three products were then treated with butyamine (BuNH2) in the presence of iodobenzene-diacetate (PhI(OAc)2) as a catalyst to produce aminoanthraquinones 2-(butylamino)anthracene-1,4-dione (83a), 2-(butylamino)-4-methoxyanthracene-9,10-dione(50a),2,3(dibutylamino)anthracene-9,10-dione (50b), 1-(butylamino)-4-methoxyanthacene-9,10-dione (50c), 1,4-(dibutylamino)anthracene-9,10-dione (50d) and 2-(butylamino)-1,4-dihydroxyanthracene-9,10-dione (86). In the second route, compound 6 first underwent amination to give 2-(butylamino)-1,4-dihydroxyanthracene-9,10-dione (86) (major product) and 1-(butylamino)-4-hydroxyanthracene-9,10-dione (87, minor product). Compound 86 was then subjected to reduction, alkylation and acylation separately. Reduction of compound 86 resulted in the compound 83a which is the same compound produced in the first route whereas methylation gave a mixture of 2-(butyamino)-1-hydroxy 4-methoxyanthracene-9,10-dione (86a) and 2-(butyamino)-1,4-dimethoxyanthracene-9,10-dione (86b). The acylation produced a mixture of 3-(butylamino)-4-hydroxy-9,10-dioxo-9,10 dihydroanthracene-1-yl acetate (86c), 2-(butylamino)-4-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-yl acetate (86d) and 2-(butylamino)-9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (86e). The products were characterised via a variety of physico-chemical and spectroscopic techniques, including melting point measurements, Fourier Transform Infrared Spectroscopy (FT-IR), Direct Injection Mass Spectrometry (DI-MS), Gas Chromatography Mass Spectrometry (GCMS) and also Nuclear Magnetic Resonance spectroscopy (NMR). Compound 86e exhibited strong antimicrobial activities toward Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Candida albicans and Escherichia coli (MIC values of 0.1 - 0.5 mg/mL). Meanwhile, compounds 83a, 50a, 50c, 86a, 86b and 86e showed strong activities against both human estrogen receptor positive breast cancer (MCF-7) (IC50 1.1 - 11.0 μg/mL) and human hepatocarcinoma (Hep-G2) (IC50 1.1 - 14.0 μg/mL) cell lines.
format	Thesis
qualification_level	Master's degree
author	Juhan, Siti Fadilah
author_facet	Juhan, Siti Fadilah
author_sort	Juhan, Siti Fadilah
title	Synthesis of aminoanthraquinone derivatives from quinizarin
title_short	Synthesis of aminoanthraquinone derivatives from quinizarin
title_full	Synthesis of aminoanthraquinone derivatives from quinizarin
title_fullStr	Synthesis of aminoanthraquinone derivatives from quinizarin
title_full_unstemmed	Synthesis of aminoanthraquinone derivatives from quinizarin
title_sort	synthesis of aminoanthraquinone derivatives from quinizarin
granting_institution	Universiti Putra Malaysia
publishDate	2013
url	http://psasir.upm.edu.my/id/eprint/67492/1/FS%202013%2087%20IR.pdf
_version_	1747812477430661120

Synthesis of aminoanthraquinone derivatives from quinizarin

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