Versuche zur ersten Totalsynthese des Aglycons der Cripowelline A und B und erste asymmetrische Synthese von Tropional
Amaryllidaceae alkaloids - and their subspecies Crinum – are traditional medicinal plants that have also become very important for modern medicine. At Bayer AG in Leverkusen two novel alkaloids – Cripowelline A and B – were isolated from extracts of Crinum powellii. Both alkaloids showed a broad insecticidal effect. Within this thesis two different strategies were developed, which should allow an efficient synthesis of the aglycon of the cripowellines A and B. According to the first synthetic concept a metathesis reaction should be used to build up the polycyclic ringsystem of the aglycon. In a first attempt the sidechain – containing the amid function - of the metathesis precursor was obtained starting from commercially available piperonal with a yield of 57% over four steps. The second sidechain should have been introduced by subsequent alpha-arylation. The arylation only led to poor yields on a test system, therefore no trials were carried out to get the target molecule. Alongside the desired metathesis precursor could be synthesized by addition of a benzyllithium species to a carbonyl compound. Although four different benzylic compounds could be synthesized in yields of 38 or 45% over 6 or 7 steps respectively, it was not possible to obtain the desired product, because no lithiation of the benzylic position could be achieved. In another effort towards the precursor the sidechain bearing the allylic ketone could be introduced starting from commercially available 3,4-(methylendioxy)phenylacetic acid in 19% yield over five steps. However, the reaction to the secondary amine by cleavage of the acetal and subsequent reductive amination was not successful. According to a second synthetic concept an alpha-arylation reaction should be used to build up the ringsystem. The synthesis of the desired arylation precursor was completed in nine steps using commercially available D-tartaric acid in an overall yield of 24%. The keysteps of this synthetic sequence were the oxidation of a polyfunctional building block using perruthenate as well as the generation of the methylketone by alkylation of 2-dimethylaminopropannitrile. This ketone was converted to the desired silyl enol ethers by using triethylamine and the corresponding silyltriflates. However, it was not possible to achieve alpha-arylation using the protocols of Buchwald et al., Hallberg et al. and Kuwajima et al. But it was possible to obtain the desired arylation product by using Kuwajimaïs conditions in an intermolekular highly functionalized test system. Tropional is an artificial fragrance used in many perfumes which presents a fresh, marine scent. Within this thesis the synthesis of both enantiomers of Tropional based on the SAMP/RAMP-hydrazone method developed by Enders et al. Starting from the enantiomerically pure propanale hydrazones the desired alpha-alkylated hydrazones could be obtained in yields greater than 70% by deprotonation with LDA at -100øC. Subsequent cleavage to the nitrile and reduction with DIBAL-H led to both enantiomeric forms of Tropional with a yield of 57% and 61% respectively over 3 steps. The determination of the enantiomeric excesses was successful after reduction of Tropional with borane dimethylsulfide to the corresponding alcohols. In both cases the enantiomeric excesses were determined to be 90% by chiral stationary phase HPLC. The olfactory evaluation showed remarkable differences in odour intensity and in the characteristic odour notes.
info:eu-repo/classification/ddc/540, Cripowellin A, Aglykon, Totalsynthese, Asymmetrische Synthese, Cripowellin B, Tropional, Hydrazon-Methode, Chemie, Alkaloide, Duftstoffe, Alkylierung, SAMP/RAMP-Hydrazone
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