Focus

The main focus of the organic synthesis research group is the chemical synthesis and derivatisation of organic compounds with non-trivial carbon connectivities, such as those found in polycyclic Natural Products. The design and selection of target structures is guided by a specific interest in reactivity patterns and/or a specific interest in biological phenomena. This research often follows a substrate-driven approach which relies on the use of highly modular synthetic intermediates as versatile building blocks or chemical platforms for various applications.

  • The chemical synthesis research mainly involves the development of novel strategies and methods to assemble complex polycyclic scaffolds found in Nature, focusing on multiple bond forming steps such as cycloadditions and cascade reactions. [1], [2]
  • The chemical derivatisation research focuses on the development of application-oriented versatile covalent ligation reactions (such as click-type reactions) to generate multiple functional derivatives from simple substrates or synthetic intermediates. [3]
  • A major recent theme, which encompasses both of the above general topics, consists of research directed at the design and synthesis of highly modular synthetic building blocks that allow a rapid exploration of Natural Product-like chemical space using simple and orthogonal functional group transformations. [4]
  • The concepts of versatile ligation/functionalisation reactions and modular building blocks in organic synthesis are also explored and applied in various collaborative research projects ranging from macromolecular and materials science to chemical biology. [5], [6]

publications

Publications

Doing both independent work and collaborations.

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courses

Courses

Giving courses to BSc and MSc in chemistry

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people

People

Former and current people working in the group.

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contact

Contact

For questions, do not hesitate to contact us.

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Latest publications

The latest independent publications are given below, for all independent publications and collaborations, see publications

Synthesis of Cyclopropyl Pinacol Boronic Esters from Dibromocyclopropanes

Synthesis of Cyclopropyl Pinacol Boronic Esters from Dibromocyclopropanes

The synthesis of cyclopropyl pinacol boronic esters from dibromocyclopropanes via Matteson-Pasto rearrangement is reported. The method is readily scalable and shows limited levels of stereoinduction, with a selectivity that is in part complementary to that observed in existing stereoselective borylcyclopropanation strategies. The method can be used to rapidly access borylcyclopropanes as interesting building blocks for diversely functionalized cyclopropanes.

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Dearomative (3 + 2) Cycloadditions of Unprotected Indoles

Dearomative (3 + 2) Cycloadditions of Unprotected Indoles

The (3 + 2) cycloaddition of various indoles with a dithioallyl cation affords dearomatized cyclopentannulated adducts, with complete control of regioselectivity and excellent chemo- and diastereoselectivity. The success of the reaction critically relies on the use of an excess of very strong Brønsted acid, which paradoxically prevents carbocationic side reactions. The reaction tolerates sensitive functionalities such as basic amines or free hydroxyls, and we demonstrate its use in late stage derivatization of highly functionalized, unprotected indoles.

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Regio- and Stereoselective Synthesis of C-4' Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues

Regio- and Stereoselective Synthesis of C-4' Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues

Novel C-4',C-5' cyclobutane-fused spirocyclic ribonucleoside analogues were prepared. Thermal [2 + 2] cycloaddition between dichloroketene and readily derived 4'-exo-methylene furanoses afforded a first entry to the required constrained ribofuranoses, relying on a carbonyl transposition sequence. Alternatively, an unusual stereoselective ionic [2 + 2] cycloaddition using methyl propiolate promoted by methylaluminoxane gave a complementary, more direct approach to such ribofuranoses. Further conversion to the constrained adenosine analogues revealed promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range.

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Stereodivergent Synthesis of Biologically Active Spironucleoside Scaffolds via Catalytic Cyclopropanation of 4-exo-Methylene Furanosides

Stereodivergent Synthesis of Biologically Active Spironucleoside Scaffolds via Catalytic Cyclopropanation of 4-exo-Methylene Furanosides

Cyclopropane fusion of the only rotatable carbon-carbon bond in furanosyl nucleosides (i.e., exocyclic 4'-5') is a powerful design strategy to arrive at conformationally constrained analogues. Herein, we report a direct stereodivergent route toward the synthesis of the four possible configurations of 4-spirocyclopropane furanoses, which have been transformed into the corresponding 4'-spirocyclic adenosine analogues. The latter showed differential inhibition of the protein methyltransferase PRMT5-MEP50 complex, with one analogue inhibiting more effectively than adenosine itself, demonstrating the utility of rationally probing 4'-5' side chain orientations.

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La Chimie crée son objet. Cette faculté créatrice, semblable a l’art lui-même, la distingue essentiellement de sciences naturelles et historiques.

Marcelin Berthelot, 1876