The Synthesis of gama-Alkylidenebutenolides

Reinhard      Bruckner

doi:10.2174/1385272013375300

Abstract

alpha,beta-Unsaturated gama-lactones with an alkylidene substituent in the gama-position (“gama-alkylidenebutenolides”) are well-known natural products. They vary in complexity from gama-methylenebutenolide, which is an antibiotic, to peridinin, which is an important pigment for light-harvesting in the ocean. A distinct sub-class within the gama-alkylidenebutenolides consists of the pulvinones and pulvinic acids, which are dyes found in mushrooms. A structural feature shared by all gama-alkylidenebutenolides, except the simplest, is that the Cgama=C off-ring bond is stereogenic. Therefore, in synthesis, this bond must be established stereoselectively. This is usually done in kinetically controlled reactions because the thermodynamic advantage of the Z- vs. E-configuration is often quite small. Section I is devoted to the introduction. Section II starts with the landmark syntheses of the carotenoid gama-alkylidenebutenolides peridinine and pyrrhoxanthine by Ito et al. beta-Elimination pathways from gama-(alpha-heteroalkyl)- substituted butenolides giving Z-configured gama-alkylidenebutenolides or, depending on the choice of the precursor, their E-isomers, follow as Section III. Section IV covers the metallocyclization protonolysis approach to such compounds. Section V concerns a condensation strategy leading to gama-alkylidenebutenolides from methylene-active compounds and derivatives of oxalic acid. Section VI deals with a Horner-Wadsworth-Emmons synthesis of two gama-alkylidenebutenolides starting from selectively enolized 1,2-diketones. Section VII is devoted to methods leading to gama-arylidene-alpha-aryl-beta-hydroxybutenolides (“pulvinones”). The synthetic chemistry of pulvinone-based carboxylic acids (“pulvinic acids”) follows in Sections VIII and IX focusing on condensation and rearrangement routes, respectively. In order to facilitate comparison, comprehension, and analysis, most syntheses are traced back to commercially available starting materials, and pertinent reaction details are included in the footnotes of the Schemes.

Keywords: Alkylidenebutenolides, E-configuration, metallocyclization, Horner-Wadsworth-Emmons synthesis, carotenoids peridinin, benzenesulfinate anion, trimethylsiloxylated furan, NMR spectrum, aldehydobutenolide intermediate, Stevens-Castro coupling, hydroxycinnamic acid, permethylgomphidic acid, Grob fragmentation