Research Kourosch Abbaspour Tehrani

Abstract

BIO-HArT (Biorizon Innovative and Scale up of Renewable Aromatics Technology) has as reveals from the title the goal to scale up innovative technologies for the production of renewable chemicals. Renewable since these are produced from biomass.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

Propargylic and allylic amines are important building blocks for the total synthesis of complex natural products, pharmaceuticals, and plant pesticides. In addition to their synthetic utility, some propargylic amine derivatives display interesting biological properties. The most direct access to these important synthetic blocks relies on the alkynylation of imines. Classical methodologies for the preparation of propargylic and allylic amines have usually exploited the relatively high acidity of a terminal acetylenic C-H bond to form metal acetylide reagents by reaction with strong bases. The so-formed organometallic compounds were then able to undergo nucleophilic addition to imines to form the desired products. Clearly, the strongly basic reagents employed in such reactions are incompatible with sensitive substrates, and therefore alkyne deprotonation often had to be carried out in a separate reaction step. In particular, highly functionalized imines, bearing one, two or even three halogen atoms in different positions have not been investigated at all in this respect. Recently, we investigated the catalytic conversion of α,α-dichloro aldimines to propargylic amines. None of the "classical" transition metal catalyzed alkynylations lead to the propargylic amines. Therefore, we developed a new methodology for the efficient alkynylation of α,α-dichloro aldimines with alkynes in the presence of a catalytic amount of indium(III) triflate giving rise to beta,beta-dichloropropargylic amines in good yields. The present proposal will, in the first place, make use of our newly developed indium(III) catalyzed alkynylation to further broaden the scope of this reaction to other polyhalogenated, α-monohalo- and beta-monohalo imines. Attempts will be made to develop alternative catalytic methods which make use of other, cheaper metals such as copper and iron to promote this conversion. The presence of the halogen atoms in the envisaged propargylic amines offers a unique opportunity to further elaborate these molecules and to subject them to an in depth reactivity study. So far, the combination of an electrophilic alkyne, a nucleophilic amine and a electrophilic dichloromethylene group has never been synthetically exploited. Since the 1,2-addition of an acetylide anion to the imine also generates a stereogenic C-atom, the influence of the addition of chiral ligands to the catalytic system will be investigated.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch
• Promoter: Maes Bert
• Fellow: Gadde Karthik

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Abbaspour Tehrani Kourosch
• Co-promoter: Bogaerts Annemie
• Co-promoter: Cool Pegie
• Co-promoter: Herrebout Wouter
• Co-promoter: Johannessen Christian
• Co-promoter: Meynen Vera
• Co-promoter: Tavernier Serge
• Co-promoter: Vande Velde Christophe
• Fellow: Sergueev Serguei

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

Very recently, 3 very active compounds, all with a benzo[j]phenanthridine-7,12-dione skeletal structure, against the causative agent of tuberculosis, Mycobacterium tuberculosis, were discovered. However, since the current syntheses for these compounds are inadequate to prepare sufficient quantities for further biotesting and elucidation of the mechanism of action, a number of new, efficient approaches are presented in this project . Furthermore, it is the intention to develop new syntheses of various substituted benzo[j]phenanthridine-7,12-diones, and to test these compounds for their anti-mycobacterial activiteit with the aim to achieve more active and less toxic analogues.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch
• Promoter: Blockhuys Frank
• Fellow: Smets Robert

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

(Mtb) are in high demand. In a past FWO project (G0020.10N) we synthesized and identified the class of octahydrobenzo[j]phenanthridinediones as promising antitubercular drug candidates. Ester analogs of the compound class showed a high degree of selectivity. For these compounds, we observed a sub-μM minimal inhibitory concentration against Mtb nearly 200 times lower than the 50% cytotoxic concentration against eukaryotic cells. However, the mechanism of action and the basis of selectivity remain unknown. Therefore, the general objective of this project is to study the mechanism of action of the octahydrobenzo[j]phenanthridinediones. We hypothesize a selective inhibition of mycothione reductase, a unique redox pathway in Actinobacteria, as the action mechanism. To this end,(i) we will identify the proposed target through genomic analysis of spontaneous Mtb mutants.(ii) We will validate the identified target through enzymatic and cellular approaches. (iii) In addition, we will study the activity against metabolically inactive bacilli and the synergism with existing TB drugs using state of the art models. This study will contribute to the fundamental understanding of the mechanism of action of the compound class and will add to the common knowledge on mycobacterial mycothione reductase. In the long term, the gathered knowledge could add to the development of new antitubercular drugs.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Abbaspour Tehrani Kourosch
• Fellow: Cappoen Davie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Hercules Foundation. UA provides the Hercules Foundation research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Abbaspour Tehrani Kourosch
• Co-promoter: Augustyns Koen
• Co-promoter: Herrebout Wouter
• Co-promoter: Pieters Luc
• Co-promoter: Tavernier Serge
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand FISCH. UA provides FISCH research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch
• Co-promoter: Maes Bert

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

Propargylic amines are important building blocks for the total synthesis of complex natural products, pharmaceuticals, and plant pesticides. In addition to their synthetic utility, some propargylic amine derivatives display interesting biological properties. The most direct access to these important synthetic blocks relies on the alkynylation of imines. Classical methodologies for the preparation of propargylic amines have usually exploited the relatively high acidity of a terminal acetylenic C-H bond to form metal acetylide reagents by reaction with strong bases. The so-formed organometallic compounds were then able to undergo nucleophilic addition to imines to form the desired products. Clearly, the strongly basic reagents employed in such reactions are incompatible with sensitive substrates, and therefore alkyne deprotonation often had to be carried out in a separate reaction step. In particular, highly functionalized imines, bearing one, two or even three halogen atoms in different positions have not been investigated at all in this respect. Recently, we investigated the catalytic conversion of α,α-dichloro aldimines to propargylic amines. None of the "classical" transition metal catalyzed alkynylations lead to the propargylic amines. Therefore, we developed a new methodology for the efficient alkynylation of α,α-dichloro aldimines with alkynes in the presence of a catalytic amount of indium(III) triflate giving rise to beta,beta-dichloropropargylic amines in good yields. The present proposal will, in the first place, make use of our newly developed indium(III) catalyzed alkynylation to further broaden the scope of this reaction to other polyhalogenated, α-monohalo- and beta-monohalo imines. Attempts will be made to develop alternative catalytic methods which make use of other, cheaper metals such as copper and iron to promote this conversion. The presence of the halogen atoms in the envisaged propargylic amines offers a unique opportunity to further elaborate these molecules and to subject them to an in depth reactivity study. So far, the combination of an electrophilic alkyne, a nucleophilic amine and a electrophilic dichloromethylene group has never been synthetically exploited. Since the 1,2-addition of an acetylide anion to the imine also generates a stereogenic C-atom, the influence of the addition of chiral ligands to the catalytic system will be investigated.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch
• Fellow: Van Beek Wim

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

According to WHO estimates malaria accounted in 2010 for almost 660,000 deaths, and even more important, 220 million people suffer daily from malaria. The emerging resistance of the malarial blood parasite Plasmodium falciparum to drugs like chloroquine and the artemisinines, especially in the Mekong delta, urges the development of new anti-plasmodial compounds. Likewise, tuberculosis (caused by Mycobacterium tuberculosis) is a worldwide health problem. Several, benzo[g] isoquinoline-5,10-dione derivatives were found active against P. falciparum (chloroquine resistant) and M. tuberculosis, but suffered from strong cytotoxicity. Therefore, a medicinally driven synthetic program is proposed here for the synthesis of a wide variety of benzo[g]isoquinoline-5,10-diones and their derivatives. Instead of applying the classical "de novo" synthetic approaches these benzo[g]isoquinoline-5,10-dione analogs will be prepared by a new "diversity-oriented synthesis" approach in order to optimize their biological activity against chloroquine resistant P. falciparum and M. tuberculosis. The direct introduction of functional groups on the benzo[g]isoquinoline-5,10-dione template molecule, by means of catalytic and/or electrochemical methods holds a central place in the proposed methodology.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Erasmus Mundus. UA provides Erasmus Mundus research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

Propargylic amines are important building blocks for the total synthesis of complex natural products, pharmaceuticals, and plant pesticides. In addition to their synthetic utility, some propargylic amine derivatives display interesting biological properties. The most direct access to these important synthetic blocks relies on the alkynylation of imines. Classical methodologies for the preparation of propargylic amines have usually exploited the relatively high acidity of a terminal acetylenic C-H bond to form metal acetylide reagents by reaction with strong bases. The so-formed organometallic compounds were then able to undergo nucleophilic addition to imines to form the desired products. Clearly, the strongly basic reagents employed in such reactions are incompatible with sensitive substrates, and therefore alkyne deprotonation often had to be carried out in a separate reaction step. In particular, highly functionalized imines, bearing one, two or even three halogen atoms in different positions have not been investigated at all in this respect. Recently, we investigated the catalytic conversion of α,α-dichloro aldimines to propargylic amines. None of the "classical" transition metal catalyzed alkynylations lead to the propargylic amines. Therefore, we developed a new methodology for the efficient alkynylation of α,α-dichloro aldimines with alkynes in the presence of a catalytic amount of indium(III) triflate giving rise to beta,beta-dichloropropargylic amines in good yields. The present proposal will, in the first place, make use of our newly developed indium(III) catalyzed alkynylation to further broaden the scope of this reaction to other polyhalogenated, α-monohalo- and beta-monohalo imines. Attempts will be made to develop alternative catalytic methods which make use of other, cheaper metals such as copper and iron to promote this conversion. The presence of the halogen atoms in the envisaged propargylic amines offers a unique opportunity to further elaborate these molecules and to subject them to an in depth reactivity study. So far, the combination of an electrophilic alkyne, a nucleophilic amine and a electrophilic dichloromethylene group has never been synthetically exploited. Since the 1,2-addition of an acetylide anion to the imine also generates a stereogenic C-atom, the influence of the addition of chiral ligands to the catalytic system will be investigated.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch
• Fellow: Van Beek Wim

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

In the framework of this research project new aerobic Cu- and Fe-catalyzed oxidation reactions will be developed which allow transformation of aryl(heteroaryl)- and bis(heteroaryl)methanes/alkanes into the corresponding ketones and alcohols. The oxidation methods aim at a high atom efficiency, a low E-factor and are based on cheap base metals.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Abbaspour Tehrani Kourosch
• Co-promoter: Herrebout Wouter

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

CHEM21 is a project that will develop a broad based portfolio of sustainable technologies for green chemical intermediate manufacture aimed at the pharmaceutical industry. Initially working with the EFPIA members the collaborators of CHEM21 will analyse a number of projects that are in development to decide which the priorities are for technology development.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Abbaspour Tehrani Kourosch
• Co-promoter: Herrebout Wouter

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch
• Fellow: Rotthier Gertjan

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

Visiting Postdoctoral Fellowship under the project "Selection of bioactive quinoids and analysis of a combined drug therapy and immunoprophylaxis for the control of turberculosis".

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

In this project new synthetic methodology will be developed for the transition metal catalyzed transformation of amides into other functional groups; amines. In the research attention will be given to the unravelling of the reaction mechanism of the new synthetic processes.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Abbaspour Tehrani Kourosch
• Fellow: Verbeeck Stefan

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

We will develop new domino reactions for the synthesis of a structurally diverse collection of allylic, propargylic and homoallylic amines and aza-heterocyclic compounds. A cationic 2-aza-Cope rearrangement of α,α-dihalogenated N-homoallylaldimines, followed by a Lewis acid catalyzed reductive coupling with an alkyne leads to the title products. The use of α,α,ω-trihalogenated N-homoallylaldimines will lead to aza-heterocycles.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

The key goal of this project is to synthesise as expeditiously as possible a wide variety of functionalized aza-anthraquinones and to test them.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

This research proposal aims to (1) design innovative syntheses of new bioactive 2-azaanthraquinones (UGent, VUB), (2) evaluate specific functionalization of the 2-azaanthraquinone skeleton with respect to a SAR-study until compounds are obtained with a desired profile of bioactivity (UGent, VUB), (3) test the in vitro and in vivo toxicity of these components and their pharmacokinetics (WIV), (4) test their in vivo bacteriostatic and bactericidal potential against M. tuberculosis (WIV), (5) test their therapeutic potential in two in vivo models of latent tuberculosis in combination with post-exposure vaccination with plasmid DNA (WIV).

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: Abbaspour Tehrani Kourosch

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project