Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters
Chiral 1-arylprop-2-en-1-ols and 1-arylprop-2-yn-1-ols are useful building blocks for modern pharmaceuticals. Previous work has found that enzyme catalysis is a potential new enantioselective synthetic route to the former. We found that Candida antarctica lipase is also an effective catalyst for kin...
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University of Missouri - Kansas City
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ftproquest:oai:pqdtoai.proquest.com:1538847 2023-05-15T13:54:51+02:00 Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters Nelson, Keegan Gregory 2013-01-01 00:00:01.0 http://pqdtopen.proquest.com/#viewpdf?dispub=1538847 ENG eng University of Missouri - Kansas City http://pqdtopen.proquest.com/#viewpdf?dispub=1538847 Organic chemistry thesis 2013 ftproquest 2021-03-13T17:36:15Z Chiral 1-arylprop-2-en-1-ols and 1-arylprop-2-yn-1-ols are useful building blocks for modern pharmaceuticals. Previous work has found that enzyme catalysis is a potential new enantioselective synthetic route to the former. We found that Candida antarctica lipase is also an effective catalyst for kinetic resolution of various substituted 1 arylpropargylic acetates and haloacetates, affording the respective (R) -1 arylproargylic alcohols with high enantioselectivity (99-100% ee). By varying the substituents on both sides of the ester bond, we discovered that the deacylation of lipase is likely the rate-determining step for our catalytic system. A greater challenge is designing a dynamic kinetic resolution (DKR) system for such substrates, which combines a resolving catalyst (lipase) with a racemizing catalyst, and can potentially lead to quantitative conversion of a racemic substrate into an enantiopure product. We studied the efficacy of various transition-metal complexes for substrate racemization and will report our results for In and Cu compounds. While kinetic resolution has been performed on the 1-arylallylic acetates with excellent yield and enantioselectivity and the DKR regime has been designed, the resulting site-isolation system has required further testing and fine tuning. We have herein investigated the utilization of macroscale site-isolation as well as various factors including solvent, and acyl donor effects in order to optimize conditions of the system. Thesis Antarc* Antarctica PQDT Open: Open Access Dissertations and Theses (ProQuest) |
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PQDT Open: Open Access Dissertations and Theses (ProQuest) |
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ftproquest |
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English |
topic |
Organic chemistry |
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Organic chemistry Nelson, Keegan Gregory Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
topic_facet |
Organic chemistry |
description |
Chiral 1-arylprop-2-en-1-ols and 1-arylprop-2-yn-1-ols are useful building blocks for modern pharmaceuticals. Previous work has found that enzyme catalysis is a potential new enantioselective synthetic route to the former. We found that Candida antarctica lipase is also an effective catalyst for kinetic resolution of various substituted 1 arylpropargylic acetates and haloacetates, affording the respective (R) -1 arylproargylic alcohols with high enantioselectivity (99-100% ee). By varying the substituents on both sides of the ester bond, we discovered that the deacylation of lipase is likely the rate-determining step for our catalytic system. A greater challenge is designing a dynamic kinetic resolution (DKR) system for such substrates, which combines a resolving catalyst (lipase) with a racemizing catalyst, and can potentially lead to quantitative conversion of a racemic substrate into an enantiopure product. We studied the efficacy of various transition-metal complexes for substrate racemization and will report our results for In and Cu compounds. While kinetic resolution has been performed on the 1-arylallylic acetates with excellent yield and enantioselectivity and the DKR regime has been designed, the resulting site-isolation system has required further testing and fine tuning. We have herein investigated the utilization of macroscale site-isolation as well as various factors including solvent, and acyl donor effects in order to optimize conditions of the system. |
format |
Thesis |
author |
Nelson, Keegan Gregory |
author_facet |
Nelson, Keegan Gregory |
author_sort |
Nelson, Keegan Gregory |
title |
Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
title_short |
Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
title_full |
Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
title_fullStr |
Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
title_full_unstemmed |
Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
title_sort |
enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters |
publisher |
University of Missouri - Kansas City |
publishDate |
2013 |
url |
http://pqdtopen.proquest.com/#viewpdf?dispub=1538847 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
http://pqdtopen.proquest.com/#viewpdf?dispub=1538847 |
_version_ |
1766260992600178688 |