Sie sind hier: Startseite Forschung / Research Research (English)

Research (English)

Research of the Brückner Group

Our research interests are the total synthesis of natural products, the synthesis of biologically active analogs thereof, and - in the context of this work - the development of efficient synthetic methodology.



Among the more than 700 natural occuring carotenoids a few contain a butenolide moiety. The most prominent example of such a carotenoid is peridinin (1, Scheme 1) and the runner-up is the closely related pigment pyrrhoxanthin (not shown). These compounds are key-constituents of the light-harvesting complexes of plankton. Striving towards these and related compounds in order to find out what is so special about them, we realized a total synthesis of peridinin in 27 steps (Angew. Chem. Int. Ed. Engl. 200544, 1553-1557; Angew. Chem. Int. Ed. Engl. 200645, 4023-4027).


Scheme 1.

Research - Scheme 1


In 1990 the dye “xerulinic acid” (2, Scheme 2) was isolated from the fungus Xerulina melanotricha and reported to have a hypocholesterolemic effect different from that of the statins. Its key structural motifs are the hexaenediyne backbone and the annulated γ-alkylidenebutenolide. Through a modular approach we were able to synthesize xerulinic acid for the first time (Angew. Chem. Int. Ed. Engl. 200443, 4523-4526; Chem. Eur. J. 200511, 1610-1624).


Scheme 2.

Research - Scheme 2



Naturally Occuring Lactones with a Five-Membered Ring

Other targets of interest are tetronic acid antibiotics - like iso-gregatin D (3) - and thiotetronic acid antibiotics - like thiolactomycin (4) (Scheme 3). A further-reaching goal in this field is determining the 3D-structure of the tetronic acid derivatives kodaistatin A (5) and C (not shown) through enantioselective synthesis of its four diastereomers. Kodaistatins are inhibitors of the glucose-6-phosphate translocase. Therefore, they spur the hope for a new therapy of diabetes II. As a spin-off-result we have developed broadly applicable accesses to the pulvinone core (6) of this class of compounds.


Scheme 3.


Research - Scheme 3


For the enantioselective synthesis of β-hydroxy-γ-lactones we have established a „Sharpless-dihydroxylation / lactonization” approach (Scheme 4). This methodology allows to transform β,γ-unsaturated carboxylic esters 7 in a single step and with usually high enantioselectivities in butyrolactones 9 (Synlett 2005, 1281-1285; Chem. Eur. J. 200511, 2154-2162; Eur. J. Org. Chem. 2006, 2110-2118; ibid. 2119-2133).


Scheme 4.

Research - Scheme 4


The β-hydroxy-γ-butyrolactones 9 obtained by this method were converted into naturally occuring lactones of a wide variety of substitution patterns (Scheme 5).


Scheme 5.


 Research - Scheme 5



Polyol,Polyene Macrolide Antibiotics

The so-called polyol,polyene macrolide antibiotics are knwon for their high activity against Gram-positive bacteria and their complex structures. Our group pursues the total syntheses of four such macrolides plus selected unnatural derivatives thereof, namely mycoticin B (10), roflamycoin (12), amphotericin B, and pentamycin (Scheme 6). The syntheses of the polyol-fragments of the former two molecules were already completed in the form of building-blocks 11 and 13, respectively.


Scheme 6.


Research - Scheme 6


During the aforementioned endeavors we have developed several methods for the stereoselective construction of the 1,3-diol subunit. Originally, our “lactone→1,3-diol degradation” played a key-role in this context, more recently, the 4-step transformation of enones 14 shown in Scheme 7 (Synlett 2005, 2905-2910).


Scheme 7.

Research - Scheme 7



Further Targets in Natural Product Synthesis

Current research programs involve the total syntheses of the antimalaria diterpene isonitrile 19 and of the hexacyclic alkaloid 20 (“quaternine”), which would be the first member of the akuammiline and picrinine class to be accessed synthetically (Scheme 8).


Scheme 8. 

 Research - Scheme 8

Benutzerspezifische Werkzeuge