Iron-catalyzed regio- and stereoselective substitution of gamma,delta-epoxy-alpha,beta-unsaturated esters and amides with Grignard reagents.

When gamma,delta-epoxy-alpha,beta-unsaturated esters or amides were treated with 2 equiv of Grignard reagents in the presence of 10-24 mol % FeCl(2), regio- and stereoselective substitution of the epoxide moiety with the Grignard reagent occurred to give exclusively delta-hydroxy-gamma-alkyl or aryl-alpha,beta-unsaturated esters or amides in good yields.

A chemical biosynthesis design for an antiatherosclerosis drug by acyclic tocopherol intermediate analogue based on "isoprenomics".

Phytyl quinols, namely acyclic tocopherols, are key intermediates of tocopherol biosynthesis, but their biological activities remain unclear. We therefore investigated the structure-activity relationship of phytyl quinols to apply a chemical biosynthesis design for an antiatherosclerosis drug based on isoprenomics. We have achieved the biosynthesis-oriented design and synthesis of alpha- (TX-2254) and beta-(TX-2247) phytyl quinol as an unnatural intermediate, other gamma- (TX-2242) and delta-(TX-2231) phytyl quinol as a natural one.

Artepillin C isoprenomics: design and synthesis of artepillin C isoprene analogues as lipid peroxidation inhibitor having low mitochondrial toxicity.

We designed and synthesized isoprene analogues of artepillin C, a major component of Brazilian propolis, and investigated the inhibitory activity on lipid peroxidation of rat liver mitochondria (RLM) and RLM toxicity based on isoprenomics. We succeeded in the synthesis of artepillin C isoprene analogues using regioselective prenylation within the range from 22% to 53% total yield. Reactivity of artepillin C and its isoprene analogues with ABTS (2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)) radical cations showed only a slight difference among the molecules.