Bausteine zur Totalsynthese von Pyrrhoxanthin (English shop)

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The core topic of my doctoral thesis is the development of new strategies for the synthesis of the γ-alkylidenebutenolide unit of the carotenoid pyrrhoxanthin (1). This natural product is a component of a photosynthetically active protein complex of marine dinoflagellates, such as Gyrodinium resplendens.

For the synthesis of this light-sensitive natural product it is necessary to construct seven double bonds stereoselectively in such a way that their isomerisation is avoided.

During my doctoral work I developed two methods for the synthesis of the butenolide unit of 1, which are depicted in the following scheme.

The synthesis is based on syn-diol 3, which is the product of a regioselective dihydroxylation of the E,trans-configured alkyne dienoate 2. The latter can − formally considered − be traced back to two molecules of acetylene and 2-butynol.

Both synthetic routes are based on the anti-elimination of H2O from alcohol 6, which leads to the Z-configured γ-alkylidenebutenolide. For this transformation I used a method developed and established in our research group that makes use of Mitsunobu conditions. Although 7 possesses an activated ester in the form of the trifluoroethyl ester, its reduction alongside the butenolide was not possible.

The synthesis presented here also served as a starting point for methodological investigations. Thus, in connection with the synthesis of butenolide 4, I studied the hydrostannylation of γ,δ-dihydroxylated propiolic acid esters.

In addition, I investigated in detail the problem of regioselectivity in the aforementioned dihydroxylation of α,β,γ,δ-unsaturated dienoates, such as 2 → 3. It turned out that the use of a trifluoroethyl ester leads in all cases to a preference for dihydroxylation of the γ,δ-double bond, and that the α,β-dihydroxy isomer is often no longer formed. I attribute this increase in selectivity to the strongly electron-withdrawing character of the trifluoroethyl group. The scope of this work is illustrated by the adjacent scheme.

The last weeks of my doctoral work were devoted to the synthesis of advanced building blocks for the completion of the first total synthesis of enantiomerically pure pyrrhoxanthin (1). Among other things, I succeeded in synthesising the two building blocks 14 and 15 shown below, which represent the entire carbon skeleton of pyrrhoxanthin (1).