Interested in a Master thesis?
There is plenty of opportunity to start working on a Bachelor or Master thesis in the Lindel research group, or to participate as an advanced research student. Bachelor theses topics are usually closely associated with doctoral student's topics. Students are encouraged to contact their laboratory assistants. We will then work out a clearly defined topic together.
Below you find a list of topics suitable for a Master thesis and beyond. Feel free to contact me directly. The list is not complete and you may also propose something convincing of your own.
Towards the marine diterpene calyculone A
Calyculone A from the marine coral Eunicea calyculata belongs to a small group of diterpenes sharing the cubitane skeleton. The compound is cytotoxic in the nanomolar range and features a twelve-membered ring. During our enantioselective synthesis of the natural product cubitene we discovered that [8.2.2] bicycles can serve as synthetic intermediates towards cubitanoids. In the first part of the thesis, a C20 aldehyde is to be synthesized. The subsequent samarium diiodide-mediated cyclization to the bicycle still needs optimization. From there, a sequence to a dihydrocalyculone is feasible, which would be a major step forward in the project.
Assembly of the bisepoxide moiety of salarin C
The salarins are intriguing macrocyclic polyketides from the marine sponge Fascaplysinopsis sp., among which salarin C is the most cytotoxic compound. We have already been successful in assembling the macrocyclic structure. However the bisepoxide moiety and the long side chain are still missing. To change that an efficient enantioselective approach has to be developed that has to provide a building block that can be coupled to the oxazole moiety or other replacing heterocycles in a C-C coupling reaction. A double Sharpless epoxidation would not directly afford the correct relative configuration. So think about it!
Azidohemiasterlin: synthesis and photoreactivity
Following up on the total synthesis of the highly cytotoxic tubulin binder hemiasterlin, we are now heading for the synthesis of a photoreactive hemiasterlin analog that could bind selectively to tubulin. For that purpose, the tryptophan section of hemiasterlin is to be replaced by a 2-azidobenzimidazole moiety, which will form a nitrene after irradiation. We expect that the biological activity of such a derivative will still be very high. Key issue will be the synthesis of the N-terminal amino acid from L-serine by reaction with a suitably N-protected benzimidazole unit, to be followed by coupling with the known C-terminal peptide and in vitro assays.
Pt(II)-catalyzed cyclization towards raputindole A
In course of the total synthesis of rac-raputindole A, we discovered that indoline-functionalized propargyl acetates undergo cyclopentannulation on treatment with platinum(II)diiodide. It is time to develop an enantioselective approach, which could be possible by employing chiral ligands. We speculate that such a cyclization would be enantioconvergent, if the acetoxy unit undergoes two subsequent 1,2-shifts rather than a stereospecific 1,3-shift. The chiral HPLC system for determining the ee has already been set up. We are waiting for a dedicated master student.
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Synthesis and fluoresence of photoageladine A
Ageladine A from the sponge Agelas sp. is one carbon atom shorter than the other pyrrole−imidazole alkaloids and features an imidazopyridine partial structure. The fluorescent natural product can be synthesized by Pictet-Spengler condensation of N-Boc-4,5-dibromo-2-formylpyrrole with 2-aminohistamine. Replacement of the amino by an azido group has not been achieved, yet, and would be one goal of the master thesis. The story would become very interesting, if nucleophiles could be incorporated on irradiation via a triazaxylylene intermediate, ideally accompanied by changing fluorescence.
Software topic: HMBC-restricted structure generator
This is a computational project, but it is not about quantum chemical calculations. Goal is the programming of a computer software that would allow the generation of all structures being in agreement with a given molecular formula and 2D NMR-derived connectivities. Interpretation of HMBC correlations has to include 4J and 5J HC couplings. Ideally, a chemistry-based ranking of the generated proposals is to be implemented already during the generation of the search tree. The software would be of help for solving many structure elucidation problems, in particular, it only a few signals in the 1H NMR spectrum are available. Any nerd out there?
