Asymmetric Total Synthesis of (-)-Quinocarcin
Quinocarcin synthesis « Naturalproductman’s Blog
Transition-metal-catalyzed reactions have the potential to provide significant improvements to the syntheses of complex target molecules. These reactions can be used to achieve a variety of different atom-economical transformations and cascade reactions and, therefore, provide access to synthetic strategies that would otherwise be unavailable using classical organic chemistry. To exemplify the utility of the latest transition-metal-catalyzed reactions for the construction of important target structures, we have been involved in the total synthesis of natural products bearing widely known chemical scaffolds. In this account, we report our recent studies on the use of a palladium-catalyzed cascade cyclization reaction and a gold(I)-catalyzed hydroamination reaction for the construction of the core structures of alkaloids, as well as their application to the total syntheses of lysergic acid, lysergol, isolysergol, and quinocarcin. 1 Introduction 2 Ergot Alkaloid Synthesis 2.1 Construction of the Core Structure by Palladium-Catalyzed Cascade Cyclization 2.2 Asymmetric Total Syntheses of (+)-Lysergic Acid and ÂRelated Alkaloids 3 Quinocarcin Synthesis 3.1 Construction of the Core Structure by Gold-Catalyzed ÂHydroamination 3.2 Asymmetric Total Synthesis of (-)-Quinocarcin 4 Concluding Remarks
A total synthesis of (+,-)-quinocarcin - Rice Scholarship …
This isoquinoline-forming aryne annulation reaction is further employed in a concise asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic, (–)-quinocarcin. In addition to this key transformation, the synthetic route features an auxiliary-mediated diastereoselective dipolar cycloaddition to set the absolute stereochemistry and a novel two-step reduction to form the tetrahydroisoquinoline. In total, this strategy has enabled the shortest total synthesis of this important alkaloid reported to date.