Rearrangement of Germacranolides. Synthesis and Absolute Configuration of Elemane and Heliangolane Derivatives from Cnicin

Abstract

A study of the Cope rearrangement of 15‐oxo‐germacranolides to 15‐oxo‐elemanolides has been carried out. The synthesis of two natural elemanolides, isolated from Centaurea paui, and an efficent isomerization of the C‐4/C‐5 double bond of 15‐oxo‐germacranolides to form heliangolides are reported. The absolute configuration of all the compounds has been ascertained. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Antimalarial sesquiterpene lactones from Distephanus angulifolius

“…3 confirms the position of H-3b, H-6, H-9b and the acetyl group above the plane, and thus the Z-configuration of the C1-C10 double bond. These observations and comparison of the negative optical rotation (½a 20 D = À9.2) of 1 with the optical rotation of a related structure with 6R,7R,8S configuration (Roselli et al, 2003), leads to the 1(10)-Z,4-E,6R,7R,8S configuration of 1. Compound 1 is a new compound for which the name vernangulide A is proposed.…”

Cytotoxic Activity of Some Natural and Synthetic Sesquiterpene Lactones

“…The elemane 9 was also previously isolated as a natural product from Centaurea paui [11]. All experimental details for these reactions as well as the physical and spectroscopic data of the compounds, mentioned above, have been previously published [12].The elemane 11 [13] was isolated from Centaurea cineraria subsp. umbrosa.…”

“…Synthetic elemane (4 and 9) and heliagolane (5 and 10) analogues showed increased activity over the parent germacranolides 1 and 8, respectively. The isolation of the cnicin and the synthesis of its derivatives were previously described [12]. Compound 11 was isolated from Centaurea cineraria subsp.…”

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

“…It is important to point out that in nature this isomerization of germacranes can be catalyzed by different mechanism. For example, other cis/trans transformations have been biomimetically catalyzed by SeO 2 [8,69–71]. The only remaining route for the thermal transformation of 1 into 3 is path O.…”

“…In some cases, these transformations are so favorable that it has been mentioned that the observed elemanes are only artifacts produced at the extraction [5–8]. It is known that 1,5-dienes suffer Cope rearrangements at temperatures between 200 and 300 °C, but some structural changes in the diene, such as the anionic oxy-Cope transformation allows the reactions to happen at temperatures below 0 °C [9].…”