22 SYNTHESIS OF TERPENOID DIALDEHYDES

Abstract

1. Synthesis of Polyfunctional Iridoids. 8,10-Dehydro-dehydrologanin was settled on as a versatile key intermediate for the synthesis of polyfunctional iridoids. Bicyclic β-ketoester derivative prepared from cis-1,2,3,6-tetrahydrophthalic anhydride was converted into α,β-unsaturated aldehyde by the following sequence: (1) acetalization, (2) OsO_4-NaIO_4oxidation (3) internal aldol condensation. α,β-Unsaturated aldehyde was successfully transformed into key intermediate by the sequence involving quantitative deconjugation of α,β-unsaturated ester followed by OsO_4-NMO-NaIO_4oxidation. Optically active key intermediate was synthesized from natural geniposide in high yield by the sequence involving Evans rearrangement of allyl phenyl sulfoxide derivative. Dehydrologanin aglycone was synthesized from key intermediate by treatment with phenyl thiolate followed by desulfurization. Sythesis of seco-loganin aglycone was achieved by the new method utilizing oxidative cleavage of γ-hydroxy alkylstannane prepared from key intermediate by stannylation followed by NaBH_4 reduction. Penstemide aglycone was synthesized from genipin in high yield. 2. Synthesis of Manoalides. Manoalide is a sesterterpene isolated from the sponge, Luffariella variabillis and was found not only to show remarkable gram positive activity but also to inactivate purified phospholipase A_2 which is an enzyme found in several neurotoxic venom and is also a rate limiting enzyme in phospholipid metabolism and prostaglandin synthesis. Manoalide and seco-manoalide were synthesized from methyl 7,8-dihydro-β-ionylidene acetate in high yield by the new method utilizing regioselective singlet oxygen oxidation of 3-alkenyl-5-trimethylsilyl furan to β-alkenyl-γ-hydroxybutenolide.