ABSTRACT
A common strategy for the stereoselective and protecting group-free total synthesis of the myxobacterial antibiotics myxothiazole Z, (14S)-melithiazole G and (14S)-cystothiazole F is described featuring an asymmetric organocatalytic transfer hydrogenation, a palladium-catalyzed Stille coupling and a cross-metathesis as the key steps.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Thiazoles/chemical synthesis , Anti-Bacterial Agents/chemistry , Catalysis , Hydrogenation , Palladium/chemistry , Stereoisomerism , Thiazoles/chemistryABSTRACT
The enantioselective total synthesis of the dual-specificity phosphatase inhibitor (-)-bitungolide F has been achieved using two convergent routes. Both strategies feature an asymmetric boron-mediated pentenylation, a stereoselective aldol, and a hydroxyl-directed 1,3-anti-reduction in order to control the stereogenic centers at C4, C5, C9, and C11. Whereas the first total synthesis was achieved in 11 steps and 14.6% overall yield using an Evans-type asymmetric alkylation, the second was completed in 9 steps and 11.4% overall yield using a highly enantioselective organocatalytic Michael addition as a key step and a protecting group free strategy.
