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
Transition metal- and lipase-catalyzed reactions: Dynamic resolutions, hydrogen transfer and enzyme engineering
Stockholm University, Faculty of Science, Department of Organic Chemistry. (Jan-Erling Bäckvall)
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis mainly focuses on chemoenzymatic processes and can be divided into three parts: The first part of the thesis, chapters 2-4, is devoted to the development of combined ruthenium- and enzyme-catalyzed dynamic processes. In these processes the metal catalyst racemizes (epimerizes) the alcohol substrate via hydrogen transfer and the enzyme transforms the substrate into enantiomerically enriched product. Chapter 2 focuses on bicyclic diols, where a process was developed to provide the enantiomerically pure product diacetates in high yield. The diacetates were then hydrolyzed using various protocols to yield the corresponding enantio- and diastereoenriched diols. Two of the substrates were mono-oxidized to yield the enantioenriched hydroxyketones in high yield. One of the hydroxyketones was subsequently employed in the formal synthesis of Sertraline in a highly enantioselective manner. Chapter 3 deals with the application of dynamic kinetic resolution in the synthesis of a pesticide derivative, which is obtained in high yield and high enantiomeric excess. Chapter 4 describes the use of dynamic kinetic resolution to set the configuration of a non-activated stereocenter in primary alcohols by taking advantage of the intermediate aldehydes intrinsic enolization behavior. A wide range of primary alcohols with a stereogenic center in β-position were dynamically resolved using this approach.

The second part, chapters 5-6, deals with different types of enzyme engineering. In chapter 5, a lipase from Pseudomonas aeruginosa was mutated using directed evolution to increase the enantioselectivity of the lipase towards an allenic substrate. In chapter 6, a racemization catalyst was anchored to the active site of both cutinase and Candida Antarctica lipase.

In the last part, chapter 7, an immobilized transition metal catalyst was used in transfer hydrogenation, a process which is closely related to the racemization of alcohols. The catalyst was used to reduce carbonyl compounds to the corresponding alcohols and was applicable to a wide range of substrates.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University , 2009. , 58 p.
Keyword [en]
Dynamic kinetic resolution, dynamic kinetic asymmetric transformation, hydrogen transfer, directed evolution, enzyme engineering
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-31386ISBN: 978-91-7155-955-5 (print)OAI: oai:DiVA.org:su-31386DiVA: diva2:276803
Public defence
2009-12-15, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 5: Manuscript. Paper 6: Manuscript.Available from: 2009-11-26 Created: 2009-11-11 Last updated: 2011-02-25Bibliographically approved
List of papers
1. Asymmetric synthesis of bicyclic diol derivatives through metal and enzyme catalysis: Application to the formal synthesis of sertraline
Open this publication in new window or tab >>Asymmetric synthesis of bicyclic diol derivatives through metal and enzyme catalysis: Application to the formal synthesis of sertraline
2010 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 16, no 13, 4031-4036 p.Article in journal (Refereed) Published
Abstract [en]

Enzyme- and ruthenium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of bicyclic diols to their diacetates was highly enantio- and diastereoselective to give the corresponding diacetates in high yield with high enantioselectivity (99.9 % ee). The enantiomerically pure diols are accessible by simple hydrolysis (NaOH, MeOH), but an alternative enzyme-catalyzed ester cleavage was also used to give the trans-diol (R,R)-1 b in extremely high diastereomeric purity (trans/cis=99.9:0.1, >99.9 % ee). It was demonstrated that the diols can be selectively oxidized to the ketoalcohols in a ruthenium-catalyzed Oppenauer-type reaction. A formal enantioselective synthesis of sertraline from a simple racemic cis/trans diol 1 b was demonstrated.

Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA, 2010
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-47342 (URN)10.1002/chem.200903114 (DOI)000276735900020 ()
Funder
Swedish Research Council
Note
authorCount :3Available from: 2010-12-01 Created: 2010-12-01 Last updated: 2017-12-12Bibliographically approved
2. Synthesis of a neonicotinoide pesticide derivative via chemoenzymatic dynamic kinetic resolution
Open this publication in new window or tab >>Synthesis of a neonicotinoide pesticide derivative via chemoenzymatic dynamic kinetic resolution
2009 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 74, no 19, 7407-7410 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-30231 (URN)10.1021/jo9014276 (DOI)000270039300025 ()
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
3. Dynamic kinetic resolution of primary alcohols with an unfunctionalized stereogenic center in the beta-position
Open this publication in new window or tab >>Dynamic kinetic resolution of primary alcohols with an unfunctionalized stereogenic center in the beta-position
2007 (English)In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 349, 1577-1581 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-22519 (URN)10.1002/adsc.200700222 (DOI)
Available from: 2007-08-09 Created: 2007-08-09 Last updated: 2017-12-13Bibliographically approved
4. Directed evolution and axial chirality: optimization of the enantioselectivity of Pseudomonas aeruginosa lipase towards the kinetic resolution of a racemic allene
Open this publication in new window or tab >>Directed evolution and axial chirality: optimization of the enantioselectivity of Pseudomonas aeruginosa lipase towards the kinetic resolution of a racemic allene
Show others...
2007 (English)In: Chemical Communications, ISSN 1359-7345, Vol. 20, 1913-1915 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-22367 (URN)10.1039/b700849j (DOI)000246723000010 ()
Available from: 2007-06-20 Created: 2007-06-20 Last updated: 2010-01-25Bibliographically approved
5. Site-Specific Covalent Immobilization of a Racemization Catalyst onto Lipase-containing Beads
Open this publication in new window or tab >>Site-Specific Covalent Immobilization of a Racemization Catalyst onto Lipase-containing Beads
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The synthesis and application of the novel heterogeneous bifunctional catalyst CALB-5 as a racemization and resolution catalyst for the dynamic kinetic resolution is described. The semisynthetic ruthenium lipase hybrid CALB-5 was obtained by inhibiting CALB beads with the novel ruthenium phosphonate complex 5 possessing a lipase active site-directed phosphonate group. By partially inhibiting the lipase beads with 5, a bifunctional catalytic system was obtained. Racemization, by the Ru-catalytic site, gave 0% ee after 24 h, and the kinetic resolution, enzymatic acylation by the uninhibited CALB sites, gave 28% conversion of 1-phenylethanol after 3 h with >99% ee of the acetylated product. A dynamic kinetic resolution experiment of (S)-1-phenylethanol with CALB-5 gave the acylated (R)-product in 18% yield and with >99% ee.

National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-31311 (URN)
Available from: 2009-11-10 Created: 2009-11-10 Last updated: 2010-01-25Bibliographically approved
6. Hydrogenized Wilkinson´s Catalyst for Transfer Hydrogenation of Carbonyl Compounds
Open this publication in new window or tab >>Hydrogenized Wilkinson´s Catalyst for Transfer Hydrogenation of Carbonyl Compounds
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Combining the advantages of homogeneous and heterogeneous catalysis is possible by heterogenization of homogeneous transition metal complexes based on a grafting/anchoring technique. Wilkinson’s catalyst ((RhCl(PPh3)3) immobilized on common silica showed high activity and selectivity in transfer hydrogenation reactions of different carbonyl compounds in isopropanol. Reactions conducted at reflux in isopropanol afforded the corresponding carbinols in high yields in short reaction times. The heterogeneous feature of the catalyst allows easy recovery and efficient reuse in the same reaction up to 5 times without loss of catalytic activity.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-31385 (URN)
Available from: 2009-11-11 Created: 2009-11-11 Last updated: 2010-01-25Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Krumlinde, Patrik
By organisation
Department of Organic Chemistry
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 254 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