Process for preparation (-)-Clausenamide and its derivatives.

Abstract

Title compds. I (R1 and/or R2 = H, halo, C1-6 alkyl, alkoxy, methylenedioxy, or nitro) were synthesized by esterification chiral alc. (such as (+)-menthol, (+)-8-phenylmenthol, or (+)-8β-naphthalenylmenthol) with chloroacetyl chloride, allowing to react with benzaldehyde or R1 substituted benzaldehyde to obtain chiral 3-(R1-phenyl)-2,3-epoxypropanoic acid chiral alkyl ester; further transesterification to obtain chiral Me ester; after condensation with 1-(R2-phenyl)-2-methylaminoethanol and oxidn., gave chiral N-[2-(R2-phenyl)-2-oxoethyl]-N-methyl-3-(R1-phenyl)-2,3-epoxypropanamide. Intramol. cyclization in the presence of base (such as LiOH, NaOH, KOH, Li diisopropylamide, Li butylate, etc.) in solvent (such as water, methanol, and/or other lower alc.) to obtain 4-(R1-phenyl)-5-(R2-benzoyl)-3-hydroxy-1H-methyl-2-pyrrolidone, further redn. with sodium boronhydride, giving the product. The racemic intermediate II can be resolved chem. with chiral agent (such as L-menthyloxyacetic acid, camphorsulfonic acid, (-)-S-phthalimidoalanine, or N-toluenesulfonylproline), and biol. with hydrolysis enzyme produced by microorganism such as Achromobacter, Alcaligenes, Archrobacter, Bacillus, Breubacillus, etc. The (-)-clausenamide may be used to increase the intelligence and delay aging. [on SciFinder(R)]