Enzymatic Synthesis of O-Heterocyclic Scaffolds by Cyclization & Ring Expansion Reactions

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School of Chemical Engineering | Doctoral thesis (article-based) | Defence date: 2018-12-05
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Date

2018

Department

Kemian ja materiaalitieteen laitos
Department of Chemistry and Materials Science

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Mcode

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Language

en

Pages

124 + app. 38

Series

Aalto University publication series DOCTORAL DISSERTATIONS, 235/2018

Abstract

The assembly of complex molecular frameworks is one of the major tasks of an organic chemist. Over the past decades, numerous tactics for the construction of such complex entities have emerged. To fulfill these tasks, classical methods often require the use of orthogonal protecting group strategies to preserve the molecular integrity, however, these tactics become more and more challenging and insufficient as the molecule gains in complexity. In this regard, enzymes offer the possibility to manipulate or implement delicate functionalities without the need for protecting groups. With the tremendous developments in the field of protein engineering in order to easily access recombinant enzymes, biocatalysis is increasingly gaining importance in organic synthesis. Heterocycles are key parts of the synthetic-organic target scope and thus, their efficient assembly represents a pivotal task in modern chemistry where particularly the stereoselective construction of these building blocks poses a crucial and recurring challenge. As the general theme of this thesis, the presented work features the application of chemoenzymatic methods for the synthesis of heterocyclic building blocks where novel biocatalytic approaches have been developed that imitate non-natural, classical chemical processes. Especially the so-called Achmatowicz rearrangement, the oxidative ring expansion of furfuryl alcohols and amines to six-membered O- and N-heterocycles, respectively, plays a central role in the thesis. Both synthetic routes to access the required substrates, as well as their application in the Achmatowicz rearrangement to prepare pyranones and piperidinones, is described. Here, a novel method to prepare furfurylamines, as well as a new lipase-mediated Achmatowicz rearrangement, is presented. Moreover, the versatility of the newly developed methods is demonstrated in a multi-catalytic natural product synthesis. Additionally, in the perspective to extend the biocatalytic toolbox, investigations on a biocatalytic decomposition of diazo compounds as a trigger for sigmatropic oxonium ylide rearrangements is presented, where lytic polysaccharide monooxygenases are reported for the first time to act as a catalyst in a protein-mediated Kirmse rearrangement.

Description

Supervising professor

Deska, Jan, Prof., Aalto University, Department of Chemistry and Materials Science, Finland

Keywords

biocatalysis, Achmatowicz reaction, Kirmse rearrangement, ring expansion, heterocy-clic chemistry, natural products, promiscuity, non-natural activity

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Parts

  • [Publication 1]: Fabian Blume, Mhd Haitham Albeiruty, Jan Deska, Alkylative Amination of Biogenic Furans through Imine-to-Azaallyl Anion Umpolung, Synthesis 2015, 47, 2093−2099.
    DOI: 10.1055/s-0034-1380201 View at publisher
  • [Publication 2]: Fabian Blume, Yu-Chang Liu, Daniel Thiel, Jan Deska, Chemoenzymatic Total Synthesis of (+)- & (−)-cis-Osmundalactone, Journal of Molecular Catalysis B: Enzymatic 2016, 134, 280−284. Full Text in Aaltodoc/Acris: http://urn.fi/URN:NBN:fi:aalto-201703233190.
    DOI: 10.1016/j.molcatb.2016.11.010 View at publisher
  • [Publication 3]: Fabian Blume, Petra Sprengart, Jan Deska, Lipase-Induced Oxidative Furan Rearrangements, Synlett 2018, 29, 1293−1296.
    DOI: 10.1055/s-0036-1591889 View at publisher
  • [Publication 4]: Daniel Thiel, Fabian Blume, Christina Jäger, Jan Deska, Chloroperoxidase-Catalyzed Achmatowicz Rearrangements, European Journal of Organic Chemistry 2018, 20, 2717−2725. Full Text in Aaltodoc/Acris: http://urn.fi/URN:NBN:fi:aalto-201806253501.
    DOI: 10.1002/ejoc.201800333 View at publisher

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https://urn.fi/URN:ISBN:978-952-60-8318-6

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[diss] Kemian tekniikan korkeakoulu / CHEM