Unified Total Synthesis of Hetiamacins A–D

A concise enantioselective total synthesis of hetiamacin A has been accomplished from a known l-aspartic acid derivative by an eight-step sequence that features ammonolytic opening of the γ-lactone moiety of amicoumacin C followed by 1,3-oxazinane ring formation in one pot. Hetiamacins B–D with putatively assigned stereochemistries have also been synthesized from amicoumacin C, each in three steps involving tetrahydro-4(1H)-pyrimidinone ring formation. The excellent NMR spectroscopic agreement of the synthetic materials with the corresponding natural products, coupled with biosynthetic considerations, has enabled the full stereochemical assignments of hetiamacins B–D.