TA-510

Chemical Name: (?-8alpha-(3,4-Dimethoxyphenyl)-4,4aalpha,5,7,7aalpha,8-hexahydrobenzo[1,2-b:4,5-c']difuran-4,7-dione
CAS No. 133118-88-4 (diastereomer), 133163-96-9 (diastereomer)
项目整合开发状态: Clinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:Reaction of 3-furancarboxaldehyde (I) with potassium cyanide in the presence of tert-butyldimethylsilyl chloride and ZnI2 gave the O-silylated cyanohydrin (II).Addition of 2(5H)-furanone (III) to the lithium anion of (II),followed by addition of 3,4-dimethoxybenzaldehyde (V) to the intermediate (IV),yielded adduct (VI).Subsequent acid cyclization of (VI) by means of trifluoroacetic acid or methanesulfonic acid provided the tricyclic derivative (VII) as a diastereomeric mixture.Desilylation of (VII) with concomitant cyanide elimination using either tetrabutylammonium fluoride at low temperature or aqueous ammonium fluoride gave rise to ketone (VIII).This was then epimerized to the title compound by treatment with triethylamine in boiling toluene.Alternatively,desilylation of (VII) with tetrabutylammonium fluoride at room temperature provided directly the title diastereoisomer.