Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Multienzymatic Cascade Synthesis of an Enantiopure (2R,5R)-1,3-Oxathiolane Anti-HIV Agent Precursor
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry.ORCID iD: 0000-0001-5807-8343
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry.ORCID iD: 0000-0002-1533-6514
(English)Manuscript (preprint) (Other academic)
Abstract [en]

An enantiopure (2R,5R)-1,3-oxathiolane derivative was obtained using amultienzymatic cascade protocol. By employing a combination of surfactant-treatedsubtilisin Carlsberg and Candida antarctica lipase B, the absolute configuration of theresulting 1,3-oxathiolane ring was efficiently controlled, resulting in an excellentenantiomeric excess (> 99%). This enantiopure 1,3-oxathiolane derivative is a keyprecursor to anti-HIV agents, such as lamivudine, through subsequent N-glycosylation.

Keywords [en]
enzyme, subtilisin Carlsberg, Candida antarctica lipase B, HIV, 1, 3-oxathiolane
National Category
Organic Chemistry
Research subject
Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-237416OAI: oai:DiVA.org:kth-237416DiVA, id: diva2:1259055
Note

QC 20181030

Available from: 2018-10-26 Created: 2018-10-26 Last updated: 2020-05-20Bibliographically approved
In thesis
1. Dynamic Chemistry for Asymmetric Synthesis, Molecular Motion and Constitutional Exchange
Open this publication in new window or tab >>Dynamic Chemistry for Asymmetric Synthesis, Molecular Motion and Constitutional Exchange
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Living matter is built on complex dynamic systems consisting of numerus biotransformations. By exploiting the adaptive and evolutive behaviors ofmolecular matter, dynamic chemistry has developed as an important tool tounderstand the organization of nonliving matter into complex living systems.This thesis concerns three aspects of dynamic chemistry with a general focus onthe influence of different stimuli on the structures and functions of dynamicsystems.The first section focuses on dynamic kinetic resolution, where enzymes areutilized for asymmetric synthesis of an enantiopure (2R,5R)-1,3-oxathiolane. Byemploying surfactant-treated subtilisin Carlsberg and Candida antarcticalipase B, the absolute configuration of the resulting 1,3-oxathiolane ring couldbe efficiently controlled.The second section addresses the motional dynamics of configurational enamineswitch systems controlled by multiple stimuli. Complete forward and backwardrotation around the enamine C=C bond could be precisely regulated uponaddition of acid/base or metal ions. The enamine switches exhibited specificsensing ability for CuII ions in solution. Moreover, the enamines exhibitedswitchable aggregation-induced emission in the solid state, which could beapplied in the development of sensors as well as fluorescent organogel.Lastly, the enamine switches could readily undergo constitutional exchange withprimary amines under catalytic acidic conditions, resulting in dynamic enaminesystems. However, under basic conditions or in the presence of excessive acid,this process exhibited extremely slow kinetics, leading to an efficient regulationof the exchange process by controlling the switch status with regulation of pHin the system.

Abstract [sv]

Levande organismer är uppbyggda av komplexa dynamiska system avsammankopplade biokemiska transformationer. Dynamisk kemi har genom attutnyttja adaptiva och evolutionära effekter hos molekylära system utvecklats tillett viktigt verktyg för att förstå principerna som styr självorganisation av ickelevande materia. Denna avhandling behandlar tre aspekter av dynamisk kemi,med fokus på vilken påverkan olika stimuli kan ha på strukturer och funktionerhos dynamiska system.Den första sektionen fokuserar på dynamisk kinetisk resolvering, där enzymeranvänds för asymmetrisk syntes av enantiomeriskt rena (2R,5R)-1,3-oxatiolanstrukturer. Genom att utnyttja surfaktant-behandlad subtilisinCarlsberg och Candida antarctica lipas B kunde absolutkonfigurationen av denresulterande 1,3-oxatiolanringen effektivt kontrolleras.Det andra avsnittet behandlar utvecklingen av konfigurationella dynamiskaenamin-omkopplare vars rörelsedynamiska beteende kan påverkas genomstimuli. Rotation av enaminens C=C-binding kunde specifikt kontrolleras i bådefram- och bakåtriktning genom addition av syra/bas eller metalljoner.Enanminkopplingen visade även upp specifik molekylär igenkänningsförmågaför CuII-joner i lösning. Vidare uppvisade enaminen reversibeltaggregationsinducerad emission i det fasta tillståndet, vilket kunde tillämpasinom utveckling av sensorer samt inom materialvetenskap.Slutligen kunde enaminomkopplaren visas genomgå reversibelt utbyte medprimära aminer i närvaro av katalytiska mängder syra, vilket resulterade idynamiska enaminsystem. Under basiska förhållanden eller i närvaro av ettöverskott syra uppvisade denna process mycket långsam kinetik, vilket ledde tilleffektiv reglering av utbytesprocessen och full kontroll av riktning ochkonstitution hos omkopplaren genom systemets pH-värde.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2018. p. 76
Series
TRITA-CBH-FOU ; 2018:55
Keywords
dynamic chemistry, constitutional dynamic chemistry, motional dynamics, dynamic kinetic resolution, enzyme, subtilisin Carlsberg, Candida antarctica lipase B, anti-HIV, 1, 3-oxathiolane, dynamic exchange, enamines, E/Z-isomerization, molecular switches, aggregation, gelation, fluorescence., dynamisk kemi, konstitutionell dynamisk kemi, molekylär rörelsedynamik, dynamisk kinetisk resolvering, enzym, subtilisin Carlsberg, Candida antarctica lipase B, anti-HIV, 1, 3-oxatiolan, dynamisk utbyte, enaminer, E/Z-isomerisering, molekylära omkopplare, aggregering, gelbildning, fluorescens.
National Category
Organic Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:kth:diva-237420 (URN)978-91-7873-000-1 (ISBN)
Public defence
2018-12-05, F3, Lindstedtsvägen 26, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20181030

Available from: 2018-10-30 Created: 2018-10-26 Last updated: 2020-05-20Bibliographically approved

Open Access in DiVA

No full text in DiVA

Authority records BETA

REN, YansongHu, LeiRamström, Olof

Search in DiVA

By author/editor
REN, YansongHu, LeiRamström, Olof
By organisation
Organic chemistry
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 154 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf