Enantioselective Synthesis And Absolute Configuration Determination Of Hydroxywilfordic Acid In Sesquiterpene Pyridine Alkaloids

An enantioselective synthetic route to hydroxywilfordic acid, a key subunit of sesquiterpene pyridine alkaloids such as wilfortrine, was developed. Asymmetric cyanation using Jacobsen's (R,R)-amino-thiourea and hydrolysis were performed to afford chiral -hydroxy--methyl acid as the (S)-isomer. Naturally derived hydroxywilfordate prepared by methanolysis of wilfortrine was found to be the (R)-isomer upon comparison with the synthetic compound.