Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach

Radical cyclisation is a method have been reported to successfully cyclise either C=C (alkene) or alkyne (C≡C) in the attempt of making heterocyclic compounds. New approach has been done in this research where nitrile group (C≡N) proved to cyclise the desired lactones. Atranone F which is a natural...

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Main Author:	Mohd Fauzi, Nawwar Fathiah
Format:	Thesis
Language:	English
Published:	2013
Subjects:	Lactones Acylation
Online Access:	http://psasir.upm.edu.my/id/eprint/38850/1/FS%202013%2026%20IR.pdf
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spelling	my-upm-ir.388502016-03-31T10:01:26Z Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach 2013-05 Mohd Fauzi, Nawwar Fathiah Radical cyclisation is a method have been reported to successfully cyclise either C=C (alkene) or alkyne (C≡C) in the attempt of making heterocyclic compounds. New approach has been done in this research where nitrile group (C≡N) proved to cyclise the desired lactones. Atranone F which is a natural product that was isolated from toxigenic fungus named Stachybotrys chartarum was chosen for the synthesis of lactones analogues in this research. Atranone F contains both 5-membered ring (γ) and 6-membered ring (δ) lactones which have many applications in medicines and agricultures. Analogue structures of both γ- and δ-lactones were prepared from their corresponding cyanohydrins via 2 steps of reactions; 1) acylation and 2) radical cyclisation. For the acylation reaction, three α-cyanobromoesters; 1-cyanoethyl 2-bromopropanoate (75e), 1-cyanocyclohexyl 2-bromopropanoate (75f) and 1-cyanoethyl 2-bromoethanoate (75g) together with four β-cyanobromoesters; 1-cyanopropan-2-yl 2-bromopropanoate (77e), 1-cyano-2-methylpropan-2-yl 2-bromopropanoate (77f), 1-cyanopropan-2-yl 2-bromoethanoate (77g) and 1-cyano-2-methylpropan-2-yl 2-bromoethanoate (77h) have been successfully synthesized. In total, five new esters have been produced including (75f), (75g), (77e), (77f) and (77g). All esters products were cyclised to lactones using radical chemistry under the treatment with tris(trimethylsilyl)silane (TTMSH) and azobisisobutyronitrile (AIBN) in toluene. Three analogue structures of γ-lactone; 4-amino-3,5-dimethylfuran-2-one (78e), 4-amino-5-cyclohexyl-3-methyl-3-ene-2-one (78f, new compound) and 4-imino-5-methylfuran-2-one (78g, new compound) were obtained. Meanwhile, four analogue of δ-lactone have been synthesized (all new compounds); 4-imino-5-hydro-3,6-dimethylpyran-2-one (79e), 4-amino-5-hydro-3,6,6-trimethylpyran-2-one (79f), 4-imino-3,5-dihydro-6-methylpyran-2-one (79g) and 4-imino-3,5-dihydro-6,6-dimethylpyran-2-one (79h). Two types of biological activities have been carried out on the cyanobromoesters and the lactones produced in order to determine their activities; 1) Ichthyotoxic test and 2) Cytotoxic assays. Esters 75e, 75f, 75g and 77g showed strong ichthyotoxic activity with TLM values of 6.26, 4.00, 2.85 and 4.00 ppm respectively. For the cytotoxic test, esters 75f, 75g, 77e, 77g, 77h and lactone 79h showed good to moderate activity against HL60 cell lines (% viability: 7.1-40.1). Lactones Acylation 2013-05 Thesis http://psasir.upm.edu.my/id/eprint/38850/ http://psasir.upm.edu.my/id/eprint/38850/1/FS%202013%2026%20IR.pdf application/pdf en public masters Universiti Putra Malaysia Lactones Acylation
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Lactones Acylation
spellingShingle	Lactones Acylation Mohd Fauzi, Nawwar Fathiah Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
description	Radical cyclisation is a method have been reported to successfully cyclise either C=C (alkene) or alkyne (C≡C) in the attempt of making heterocyclic compounds. New approach has been done in this research where nitrile group (C≡N) proved to cyclise the desired lactones. Atranone F which is a natural product that was isolated from toxigenic fungus named Stachybotrys chartarum was chosen for the synthesis of lactones analogues in this research. Atranone F contains both 5-membered ring (γ) and 6-membered ring (δ) lactones which have many applications in medicines and agricultures. Analogue structures of both γ- and δ-lactones were prepared from their corresponding cyanohydrins via 2 steps of reactions; 1) acylation and 2) radical cyclisation. For the acylation reaction, three α-cyanobromoesters; 1-cyanoethyl 2-bromopropanoate (75e), 1-cyanocyclohexyl 2-bromopropanoate (75f) and 1-cyanoethyl 2-bromoethanoate (75g) together with four β-cyanobromoesters; 1-cyanopropan-2-yl 2-bromopropanoate (77e), 1-cyano-2-methylpropan-2-yl 2-bromopropanoate (77f), 1-cyanopropan-2-yl 2-bromoethanoate (77g) and 1-cyano-2-methylpropan-2-yl 2-bromoethanoate (77h) have been successfully synthesized. In total, five new esters have been produced including (75f), (75g), (77e), (77f) and (77g). All esters products were cyclised to lactones using radical chemistry under the treatment with tris(trimethylsilyl)silane (TTMSH) and azobisisobutyronitrile (AIBN) in toluene. Three analogue structures of γ-lactone; 4-amino-3,5-dimethylfuran-2-one (78e), 4-amino-5-cyclohexyl-3-methyl-3-ene-2-one (78f, new compound) and 4-imino-5-methylfuran-2-one (78g, new compound) were obtained. Meanwhile, four analogue of δ-lactone have been synthesized (all new compounds); 4-imino-5-hydro-3,6-dimethylpyran-2-one (79e), 4-amino-5-hydro-3,6,6-trimethylpyran-2-one (79f), 4-imino-3,5-dihydro-6-methylpyran-2-one (79g) and 4-imino-3,5-dihydro-6,6-dimethylpyran-2-one (79h). Two types of biological activities have been carried out on the cyanobromoesters and the lactones produced in order to determine their activities; 1) Ichthyotoxic test and 2) Cytotoxic assays. Esters 75e, 75f, 75g and 77g showed strong ichthyotoxic activity with TLM values of 6.26, 4.00, 2.85 and 4.00 ppm respectively. For the cytotoxic test, esters 75f, 75g, 77e, 77g, 77h and lactone 79h showed good to moderate activity against HL60 cell lines (% viability: 7.1-40.1).
format	Thesis
qualification_level	Master's degree
author	Mohd Fauzi, Nawwar Fathiah
author_facet	Mohd Fauzi, Nawwar Fathiah
author_sort	Mohd Fauzi, Nawwar Fathiah
title	Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
title_short	Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
title_full	Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
title_fullStr	Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
title_full_unstemmed	Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
title_sort	synthesis of γ-lactone and δ-lactone analogues of atranone f via radical cyclisation approach
granting_institution	Universiti Putra Malaysia
publishDate	2013
url	http://psasir.upm.edu.my/id/eprint/38850/1/FS%202013%2026%20IR.pdf
_version_	1747811758404272128

Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach

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