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978-3-8439-0326-4, Reihe Organische Chemie
Studien zur Totalsynthese von Monilicin
281 Seiten, Dissertation Rheinische Friedrich-Wilhelms-Universität Bonn (2011), Softcover, A5
The development of novel biologically active compounds which can be applied e. g. in crop protection is an essential objective of organic chemistry. The present thesis focuses on the total synthesis of Monilicin, a secondary metabolite of Monilia fructicola with fungicidal properties. In the course of total synthesis, two new methods for the construction of benzopyranones were established.
In the first instance, a one-pot synthesis affording 3-alkenyl coumarins is described which were considered to be unstable. In this domino reaction ortho-hydroxy-carbonyl compounds with different electron density and steric demand can be converted with crotonic acid and its homologues in up to 97% yield. The new protocol features very mild reaction conditions and a modular concept which allows the installation of substituents at every position of the coumarin scaffold by the choice of the proper starting material. The second method describes another one-pot protocol furnishing 3-cinnamoyl-2-styrylchromones from 2,6-dihydroxyaceto-phenones and cinnamic acid chlorides in almost quantitative crude yields. Thus, highly functionalized building blocks are formed in a single step. Regarding both methods, the substrate scope was evaluated and a plausible reaction mechanism was derived.
The main body of this thesis deals with the synthetic steps towards Monilicin employing the results of the methodical part. Two strategies were elaborated to face the major challenge i.e. to construct the α,β,γ,δ-unsaturated seven-emembered lactone ring starting from 5-hydroxy-7-methylchromones. A precursor could be synthesized in seven steps with an overall yield of 16% which is suitable for the ring closure via vinylogous aldol condensation. In case of the second strategy which concludes with a macrolactonization reaction, the precursor substrate was obtained in five steps and an overall yield of 32%. The latter route is based on transformations at C-2 of 5-hydroxy-7-methylchromone which benefit from a high regioselectivity e. g. in the iodination of the chromone scaffold and the possibility to skip a protection group strategy.