hyperolactone-c and hydronium-ion

Rh(II)-catalyzed oxonium ylide formation-[2,3] sigmatropic rearrangement of α-diazo-β-ketoesters possessing γ-cyclic unsaturated acetal substitution, followed by acid-catalyzed elimination-lactonization, provides a concise approach to 1,7-dioxaspiro[4.4]non-2-ene-4,6-diones. The process creates adjacent quaternary stereocenters with full control of the relative stereochemistry. An unsymmetrical monomethylated cyclic unsaturated acetal leads to hyperolactone C, where ylide formation-rearrangement proceeds with high selectivity between subtly nonequivalent acetal oxygen atoms.

Topics: Acetals; Furans; Molecular Structure; Onium Compounds; Rhodium; Spiro Compounds; Stereoisomerism

A stereocontrolled synthesis of norphenyl hyperolactone C together with its utility as a direct precursor to the anti-HIV agent hyperolactone C and analogues by addition of organolithiums, are described. Preliminary studies to access this key building block in a catalytic enantioselective manner are also reported.

Topics: Anti-HIV Agents; Catalysis; Furans; Lithium; Onium Compounds

Starting from readily available (S)-styrene oxide an asymmetric synthesis is described of the naturally occurring anti-HIV spirolactone (-)-hyperolactone C, which possesses adjacent fully substituted stereocenters. The key step involves a stereocontrolled Rh(II) -catalysed oxonium ylide formation-[2,3] sigmatropic rearrangement of an α-diazo-β-ketoester bearing allylic ether functionality. From the resulting furanone, an acid-catalysed lactonisation and dehydrogenation gives the natural product.

Topics: Anti-HIV Agents; Catalysis; Epoxy Compounds; Furans; Molecular Structure; Onium Compounds; Rhodium; Stereoisomerism