In the present thesis, the step efficient synthesis of 3,4-dioxygenated quinolinones is described.
Initially, step efficient syntheses of other natural products were analyzed by using a color-coded
flow chart presentation. Thus, particularly powerful strategies were identified. These included
disconnection in equally sized and complex substructures, avoidance of non-strategic redox- and
functional group interconversions, as well as the usage of functional group tolerant
transformations capable of forging multiple bonds in a single step.
By applying these principles to the natural product class of 3,4-dioxygenated quinolinones, an
aryne insertion into an unsymmetric imide followed by a diastereoselective aldol reaction was
recognized.The target was thus built up from two equally sized molecules whilst the
aryne insertion yielded two new carbon – sigma-bonds in a single step. When performed in continuous
flow, the reaction proceeded within minutes, while lower yields and longer reaction times were
observed in batch. Furthermore, both aryne and imide could easily be varied so that a multitude
of differently substituted 3,4-dioxygenated quinolinones were synthesized. In total, nine natural
products, including (±)-peniprequinolone, (±)-aflaquinolones E and F, (±)-6-deoxyaflaquinolone
E, (±)-quinolinones A and B, (±)-aniduquinolone C and yaequinolones J1 and J2, were synthesized in one to three steps.
XVI, 141 Seiten
500 Naturwissenschaften und Mathematik::540 Chemie::547 Organische Chemie
Step Efficient Synthesis of 3,4-Dioxygenated Quinolones Enabled by Aryne Chemistry
Stufeneffiziente Synthese von 3,4-dioxygenierten Chinolonen ermöglicht durch Arin-Chemie
Biologie, Chemie, Pharmazie