ABSTRACT
An efficient stereoselective synthetic approach to 7-20 oxa-bridged abietane type natural products is reported. Key steps are an asymmetric Mukaiyama aldol addition to construct the C3 stereocenter and an intramolecular organocatalyzed Stetter-type Michael addition followed by a Tishchenko reaction. An intramolecular lactone-enolate arylation delivers the tetracyclic skeleton. This synthetic strategy was applied for the first total synthesis of (+)-elevenol, an antihepatitis C active compound from Fluegga virosa, and the first total synthesis of (+)-przewalskin.
Subject(s)
Abietanes/pharmacology , Antiviral Agents/pharmacology , Diterpenes/pharmacology , Euphorbiaceae/chemistry , Hepacivirus/drug effects , Abietanes/chemical synthesis , Abietanes/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Crystallography, X-Ray , Diterpenes/chemical synthesis , Diterpenes/chemistry , Microbial Sensitivity Tests , Models, Molecular , Molecular StructureABSTRACT
A highly reactive nickel catalyst comprising NiCl2(dppp) or NiCl2(dppe) with zinc powder, ZnI2 and Ph2PH, was applied in the isomerization of terminal alkenes to Z-2-alkenes. The double-bond geometry of the 2-alkene can be controlled via the reaction temperature to yield the 2-Z-alkenes in excellent yields and high Z-selectivities. The formation of other constitutional isomers, such as 3-alkenes, is suppressed on the basis of the proposed mechanism via a 1,2-hydride shift from the metal to the Ph2P ligand. The nickel-catalyzed isomerization reaction was then applied in the synthesis of (9Z,12Z)-tetradeca-9,12-dienyl acetate, a pheromone with a 2Z,5Z-diene subunit.
