Synthesis of Both Enantiomers of the Streptomyces Alkaloid 4-epi-SS20846A

Abstract

The enantiodivergent synthesis of the Streptomyces alkaloid 4-epi-SS20846A was based on a Takai olefination/Suzuki–Miyaura­ coupling sequence for the highly stereoselective introduction of the E,E-pentadienyl side chain on the piperidine skeleton. Optical separation of a key hydroxylated enamide ester, prepared by palladium-catalyzed methoxycarbonylation of a lactam-derived enol phosphate, was successfully achieved by both lipase-catalyzed kinetic resolution and semipreparative HPLC. This approach allowed us to obtain the enantiopure target alkaloid in 35–38% yield over six steps.

Key words

alkaloids - lactams - carbonylation - olefination - cross-coupling

• References

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