Total synthesis of (+)-astrophylline.
The first total synthesis of (+)-astrophylline (2) has been achieved, starting from readily available enantiomerically pure (+)-(1R,4S)-4-hydroxycyclopent-2-enyl acetate (11). A novel ruthenium-catalyzed ring-closing ring-opening ring-closing metathesis of carbocyclic olefins of general type 5 was the key step, providing the stereochemically well-defined bis-piperidyl skeleton of the target molecule. A [2,3]-Wittig-Still rearrangement of 9 was also employed as the critical transformation in the stereocontrolled generation of the 1,2-trans configuration of the cyclopentene intermediate 6c. Our early synthetic efforts toward 1,2-trans cyclopentene derivatives of type 6, as well as the synthetic pathway to an optimized 13-step total synthesis of 2 (12% overall yield), are reported.
Schaudt
Marco
M
Institut für Chemie, Technische Universität Berlin, Strasse des 17, Juni 135, D-10623 Berlin, Germany.
Blechert
Siegfried
S
D000470:Alkaloids / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D019665:Euphorbiaceae / Q000737:chemistry*; D007202:Indicators and Reagents; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010880:Piperidines / Q000032:analysis / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000470:Alkaloids; D007202:Indicators and Reagents; D010880:Piperidines; C476936:astrophylline