Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib

In this study, bicyclic moieties 3,4-fused y-lactone-y-lactam and y-lactone-pyrrolidine were chosen as the target molecules due to their highly functionalized structures and their ability to be bioactive 5,5-bicyclic molecules. The synthetic strategy was divided into three main parts in which the fi...

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Main Author: Azib, Nur Aini
Format: Book Section
Language:English
Published: Institute of Graduate Studies, UiTM 2018
Subjects:
Online Access:https://ir.uitm.edu.my/id/eprint/22027/
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author Azib, Nur Aini
author_facet Azib, Nur Aini
author_sort Azib, Nur Aini
building UiTM Institutional Repository
collection Online Access
description In this study, bicyclic moieties 3,4-fused y-lactone-y-lactam and y-lactone-pyrrolidine were chosen as the target molecules due to their highly functionalized structures and their ability to be bioactive 5,5-bicyclic molecules. The synthetic strategy was divided into three main parts in which the first part concentrated on the construction of the key-intermediates, lactam and pyrrolidine ring moieties, from D-alanine methyl ester hydrochloride. The approach involved N-protection of the starting material with either benzyl or Boc protecting groups. Condensation with methyl malonyl chloride followed by Dieckmann cyclization gave the required y-lactam ring moiety 5 which is also known as the p,pdiketoester with an overall yield of 39%. Consequently, decarboxylation of the methyl ester functional group followed by reduction of the keto amide functionality with LiAlH4 afforded the desired pyrrolidine ring 25 in 18% overall yield. The second part focused on the formation of the fused y-lactone-y-lactam and y-lactone-pyrrolidine bicyclic systems. The y-lactam ring moiety underwent C-alkylation reaction at the C3-position via insertion of the ethyl acetyl functionality by utilizing TBAF as the base. Subsequently, selective dimethoxy-carbonylation was performed using two different decarboxylating agents which were a salt-solvent system, Lil/DMF, and an acid medium, HCl/AcOH; both successfully gave decarboxylated products but the former with the presence of C-3 methyl group as anticipated and the latter without…
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spelling uitm-220272018-11-12T06:54:56Z https://ir.uitm.edu.my/id/eprint/22027/ Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib Azib, Nur Aini Organic chemistry In this study, bicyclic moieties 3,4-fused y-lactone-y-lactam and y-lactone-pyrrolidine were chosen as the target molecules due to their highly functionalized structures and their ability to be bioactive 5,5-bicyclic molecules. The synthetic strategy was divided into three main parts in which the first part concentrated on the construction of the key-intermediates, lactam and pyrrolidine ring moieties, from D-alanine methyl ester hydrochloride. The approach involved N-protection of the starting material with either benzyl or Boc protecting groups. Condensation with methyl malonyl chloride followed by Dieckmann cyclization gave the required y-lactam ring moiety 5 which is also known as the p,pdiketoester with an overall yield of 39%. Consequently, decarboxylation of the methyl ester functional group followed by reduction of the keto amide functionality with LiAlH4 afforded the desired pyrrolidine ring 25 in 18% overall yield. The second part focused on the formation of the fused y-lactone-y-lactam and y-lactone-pyrrolidine bicyclic systems. The y-lactam ring moiety underwent C-alkylation reaction at the C3-position via insertion of the ethyl acetyl functionality by utilizing TBAF as the base. Subsequently, selective dimethoxy-carbonylation was performed using two different decarboxylating agents which were a salt-solvent system, Lil/DMF, and an acid medium, HCl/AcOH; both successfully gave decarboxylated products but the former with the presence of C-3 methyl group as anticipated and the latter without… Institute of Graduate Studies, UiTM 2018 Book Section PeerReviewed text en https://ir.uitm.edu.my/id/eprint/22027/1/ABS_NUR%20AINI%20AZIB%20TDRA%20VOL%2014%20IGS%2018.pdf Azib, Nur Aini (2018) Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib. (2018) In: THE DOCTORAL RESEARCH ABSTRACTS. IGS Biannual Publication, 14 . Institute of Graduate Studies, UiTM, Shah Alam.
spellingShingle Organic chemistry
Azib, Nur Aini
Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib
title Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib
title_full Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib
title_fullStr Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib
title_full_unstemmed Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib
title_short Synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / Nur Aini Azib
title_sort synthesis of 3,4-fused y-lactone-y-lactam and y-lactonepyrrolidine bicyclic systems / nur aini azib
topic Organic chemistry
url https://ir.uitm.edu.my/id/eprint/22027/