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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
Online Access:http://psasir.upm.edu.my/id/eprint/38850/1/FS%202013%2026%20IR.pdf
http://psasir.upm.edu.my/id/eprint/38850/
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spelling my.upm.eprints.388502016-03-31T10:01:26Z http://psasir.upm.edu.my/id/eprint/38850/ Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach 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). 2013-05 Thesis NonPeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/38850/1/FS%202013%2026%20IR.pdf Mohd Fauzi, Nawwar Fathiah (2013) Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach. Masters thesis, Universiti Putra Malaysia.
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
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
author Mohd Fauzi, Nawwar Fathiah
spellingShingle Mohd Fauzi, Nawwar Fathiah
Synthesis of γ-lactone and δ-lactone analogues of Atranone F via radical cyclisation approach
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
publishDate 2013
url http://psasir.upm.edu.my/id/eprint/38850/1/FS%202013%2026%20IR.pdf
http://psasir.upm.edu.my/id/eprint/38850/
_version_ 1643832254032510976
score 13.211869

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