Totalsynthesen von (-)-Preussochromon A, (+)-Preussochromon E und (-)-Preussochromon F
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Philipps-Universität Marburg
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Abstract
Within the framework of this work, a synthetic approach to preussochromone A could be found; a dihydrothiopyran-based metabolite that is so far unique in nature. In addition, based on the work of ERIC KERSTE, a synthesis of the postulated structure of preussochromone F could be developed. Its structure is characterized by a synthetically challenging trans-annelation of a fully substituted carbocyclic five-membered ring to a chromanone skeleton. As a result of the synthesis, the wrong structure determination of the preussochromones E & F was revealed, their actual structures postulated by NMR spectroscopy and finally proven by total synthesis. The syntheses carried out proved the great value of vic-polycarbonyl compounds as potent electrophiles in diastereoselective aldol and aldol-type reactions, which were used and investigated as key steps in the synthesis of the preussochromones.
In the case of preussochromone A, a thio-MICHAEL-retro-MICHAEL reaction of an aliphatic secondary thiol to a sulfonylchromenone was found to be the first key step in the formation of the critical C,S bond. Moreover, a second key reaction and main motivation of the synthesis was developed: a LEWIS acid mediated aldol-like cycloisomerization that eventually closed the dihydrothiopyran and subsequently allowed the synthesis of preussochromone A.
The synthesis of the postulated structure of preussochromone F was based on a different approach. Due to the trans linkage of the rings, an intramolecular aldol reaction was not possible, therefore a formal 1,4-addition followed by enolate alkylation should be used to produce the trans configuration. For diastereo- and enantioselective assembly of the first stereocenters, an auxiliary-controlled MICHAEL addition, developed mainly by ERIC KERSTE, was used. A GRUBBS metathesis was finally the method of choice for the formation of the trans-cyclopentene. Through a series of challenging oxidations, preussochromone F was finally synthesized. Comparison of NMR spectra confirmed that it was not the isolated natural product. A structural revision led to a cis-linked derivative, which could subsequently be prepared by a diastereoselective intramolecular aldol reaction of a vic-tricarbonyl compound. This allowed the true structure of preussochromone F, and by subsequent reduction, that of preussochromone E to be revealed.
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Created: 2022Issued: 2022-07-04Updated: 2022-07-04
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Fachbereich Chemie
Publisher
Philipps-Universität Marburg
Language
ger
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DoctoralThesis
Keywords
Total synthesisnatural productsketo esterchromenone
DFG-subjects
TotalsyntheseNaturstoffeKetoesterChromenone
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540
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Beller, Marc Paul: Totalsynthesen von (-)-Preussochromon A, (+)-Preussochromon E und (-)-Preussochromon F. : Philipps-Universität Marburg 2022-07-04. DOI: https://doi.org/10.17192/z2022.0220.
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