Totalsynthese von Collinolacton: Darstellung des vollständigen, tricyclischen Kohlenstoffgerüsts
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Philipps-Universität Marburg
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Abstract
In the present work, a first total synthesis to build up the natural product collinolactone was investigated. This project was carried out in form of a cooperation between the two research groups VON ZEZSCHWITZ and KOERT. Three different synthetic strategies were followed. In the course of the first strategy, building block B-1 was synthesized within a ten-step sequence in an overall yield of 12%. This was then to be linked in a ZWEIFEL-olefination with a boronic acid ester synthesized by N. KLANGWART. However, this attempt failed, so the used building block-A 1 was modified in β-position to the aldehyde (contribution of N. Klangwart), whereby strategy 2 - linkage via allylation - could be successfully carried out in this work. Subsequently, starting from the obtained alcohol, the seven-membered lactone could be completed by saponification of the ethyl ester and subsequent lactonization. Ultimately, however, this strategy was discarded in favor of strategy 3, since the necessary aldehyde could only be represented by a ten-step sequence with an average overall yield of only 2%. The new building block is modified in that the enone moiety is already present in the α-position, which, after joining the two building blocks without additional reaction steps, should allow ring closure metathesis and thus closure of the middle ten-membered ring.
After successful presentation of both building blocks, they were joined together within an allylation. To build up the seven-membered lactone, the ethyl ester was subsequently saponified using trimethyltin hydroxide to give the acid. Lactonization using acetic anhydride and DBU allowed completion of the metathesis precursor.
However, the Z-isomer, rather than the desired E-isomer, turned out to be the more thermodynamically favorable and was the only product obtained. In addition, the enone unit was found not to be planar as expected and thus did not behave like a classical MICHAEL system. To build up the butadiene unit, the tertiary alcohol was obtained in 29% yield by adding MeLi to the enone.
Thus, it can be summarized that a significant contribution was made to the planned first total synthesis of collinolactone, whereby within this work the synthesis of the two building blocks and the two key steps - the linkage of the two building blocks, as well as the closing of the ten-membered ring - were established and the complete carbon skeleton of collinolactone was obtained for the first time.
What remains to be done is the dehydration to finally build up the butadienyl moiety, the reformation of the 6-membered lactone (acetal cleavage, oxidation) and the deprotection of the secondary hydroxyl function on the 7-membered lactone in order to finally synthesize collinolactone.
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Created: 2022Issued: 2023-01-30Updated: 2023-01-30
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Fachbereich Chemie
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Philipps-Universität Marburg
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ger
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DoctoralThesis
Keywords
total synthesismetathesisnatural productcyclodecatriene
DFG-subjects
CyclodecatrienTotalsyntheseNaturstoffMetathese
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540
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Gaß, Juliane: Totalsynthese von Collinolacton: Darstellung des vollständigen, tricyclischen Kohlenstoffgerüsts. : Philipps-Universität Marburg 2023-01-30. DOI: https://doi.org/10.17192/z2022.0218.
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