BUNCH Group
We are committed to research in both medicinal chemistry and organic chemistry. While our medicinal chemistry projects focus on design and synthesis of neuroactive ligands as novel tool compounds and/or potential drug candidates, our organic chemistry projects aim to discover new synthetic methodology relevant to medicinal chemistry.
The objective of our research in medicinal chemistry is to discover valuable tool compounds for studying biological mechanisms underlying health and disease in the CNS. We work closely with pharmacologists at the department and around the world to achieve these goals!
We take creative approaches in combinations with state-of-the-art computational techniques to design new valuable tool compounds for in vitro and in vivo studies. Our work span several targets:
- Ionotropic glutamate receptors (iGluRs)
- Proline analogs: ACS Chem. Neurosci. 2020, 11, 674-701 - and references herein
- Metabotropic glutamate receptors (mGluRs)
- Group III and mGlu2 agonists: J. Med. Chem. 2016, 59, 914-924
- Excitatory amino acid transporters (EAAT)
- EAAT1 NAM, UCPH-101: J. Med. Chem. 2010, 53, 7180–7191
- EAAT1 NAM, UCPH-102: ChemMedChem 2016, 11, 403-419
- EAAT1 NAM, UCPH-41003: J. Med. Chem. 2016, 59, 8757-8770
- EAAT3 NAM, UCPH-42000: ACS Chem. Neurosci. 2019, 10, 4414-29
- GABAA receptors
- Methaqualone analogs: ACS Chem. Neurosci. 2020, 11, 4362-75
- Putative 5HT2a-mGlu2 receptor complex: J. Med. Chem. 2020, 63, 9928-49
Natural products remain an important source for de-novo drug discovery. Compared to synthetic libraries, natural products comprise a higher ratio of sp3 to sp2 carbon, number of chiral centers and they are in general chemically more complex (number of functional groups pr carbon). We engage in the total synthesis of natural products with the aim of understanding their mode of action and to be able to perform a detailed SAR study.
Most recently we have reported the stereoselective total synthesis of the lactam of the neurotoxin caramboxin in only 8 steps starting from readily available allylglycine:
Published in: Chem. Eur. J. 2021, in press
We are committed to discover new synthetic methodology relevant for medicinal chemistry. This be efficient synthesis of chemically complex fragments, new planar heterocycles, new/improved protecting group chemistry and more! Recent and ongoing work is:
Expedite Synthesis of Polysubstituted meta-Halophenols
Phenols are frequent motifs in pharmaceutical agents as well as in agrochemicals. Thus, their halo-functionalized analogues are highly valuable building blocks in the synthesis thereof. We have demonstrated the expedite synthesis of polysubstituted meta-halo phenols by the first-time reported anion-accelerated 2-pi-electrocyclic ring-opening reaction:
Published in: Chem. Eur. J. 2021, 27, 10941-10947
We are now exploring further the scope and limitations of this new and exciting methodology!
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Novel Planar Heterocycles
Chemical space is enormous! It is estimated to comprise some 10(200) distinct drug-like molecules which every single one displays a unique biological activity profile. We are interested in the development of new methodology for the synthesis of new planar heterocycles as such can be incorporated in novel drug-candidates to induce target selectivity, increase potency and/or fine-tune the bioavailability profile.
We have disclosed the first synthesis of oxazolo[4,5-b]pyrazines by a new palladium-catalyzed domino reaction with an intramolecular ring closure of an N-(2-chloro-3-heteroaryl)arylamide:
Published in: Adv. Synth. & Cat. 2014, 356, 1047-1055
Highlighted in: Synfacts 2014, 10, 0578
Methods for its functionalization in collaboration with Prof. Florence Mongin, France: Eur. J. Org. Chem. 2018, 29, 3904-13
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TBAF Cleaves Boroxazolidones to Corresponding Free Amino Acids
Protection of α-amino acids with 9-borabicyclo[3.3.1]nonane (9-BBN) to give their corresponding boroxazolidones is highly attractive as it concurrently masks both the amino and the carboxylic acid functionalities. However, the required harsh methods for their deprotection have limited its use. In this work we report that tetrabutylammonium fluoride (TBAF) is a mild and versatile reagent for cleaving boroxazolidones to their corresponding free α-amino acids, in high yields.
Published in: Eur. J. Org. Chem. 2017, 1475-1478
MSc thesis positions
We welcome letter of interests from prospective MSc thesis students who are interested in medicinal chemistry projects and/or organic chemistry projects relevant for medicinal chemistry.
- Letter of motivation (1 page)
- Your CV (1 page)
- List of publications (optional)
- MSc project: NATURAL PRODUCT as leads in CNS drug discovery (pdf)
- MSc project: NEW METHODOLOGY for expedite drug synthesis (pdf)
All correspondence should be directed to Lennart Bunch.
PhD fellowship positions
We welcome letter of interests from MSc students or MSc graduates who are interested in doing a PhD in organic chemistry or medicinal chemistry. A PhD fellowship can be funded in a number of ways:
- Joint application to a public or private foundation
- Self funded
To learn more about the PhD study program at University of Copenhagen, Faculty of Health and Medical Sciences, click here. Express you interest by sending as PDF:
- Letter of motivation (1 page)
- Your CV (1 page)
- List of publications
All correspondence should be directed to Lennart Bunch.
Postdoc positions
We welcome applicants who are interested in a Postdoc position. Projects of the highest international standard are available within all our research topics. The Postdoc position can be funded in a number of ways:
- Joint application
- Self funded
If you would like to learn more about how to become a Postdoc in the group, please send as PDF:
- Letter of motivation (1 page)
- Your CV (1 page)
- List of publications
- Plan for raising funding from your own country
All correspondence should be directed to Group leader Lennart Bunch
I established my research group in 2007 and has a strong international profile comprising students and co-workers from several countries. The working environment is vibrant and ambitious, and the language of daily communication is English - both spoken and written.
Supervision
I hold biweekly project meetings with every group member, where we discuss recent progress, challenges, and goals. Aside from this, I run an open door policy everyday after 13:00. You are welcome to drop by.
Outrearch
We engage in scientific and social activities with the other chemistry groups at the department as well as with our collaborating partners.
Goals
Organic chemistry and medicinal chemistry at the highest level. Our research objectives are:
- New synthetic methodology to easily access structurally complex molecules
- New reagents with relevance for medicinal chemistry
- Design and synthesis of novel tool compounds for use by our collaborators in the studying of neurological mechanisms in the healthy and diseased brain
Group members
Name | Title | Phone | |
---|---|---|---|
Xinkai Wu | Master Thesis Student | ||
Christoffer Mentz | PhD Fellow | ||
Yasaman Doroudian | Postdoc | ||
Lennart Bunch | Professor | +4535336244 | |
Effimia Valavani | Research Fellow |
Shengxiao Qi |
External PhD student | nrz989@sund.ku.dk |