LY-418426

双环[3.1.0]己烷-2,6-二羧酸,2-氨基-4-氧基-,(1R,2R,5S,6S)-rel-Chemical Name: (1S*,2S*,5R*,6R*)-2-Amino-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid
CAS No. 215867-19-9
项目整合开发状态: Biological Testing
项目研究机构: Lilly (Originator)
合成路线:Condensation of ethyl bromoacetate (I) with dimethyl sulfide gave the sulfonium salt (II).Addition of the sulfur ylide resulting from (II) and DBU to cyclopentenone (III) produced the bicyclic compound (IV).This was converted into the silyl enolate (V),which was subsequently oxidized to the unsaturated ketone (VI) by means of palladium diacetate.Alternatively,(IV) was directly oxidized to (VI) using allyl methyl carbonate and palladium diacetate.Treatment of enone (VI) with tert-butyl hydroperoxide and DBU produced epoxide (VII),which was further converted into hydroxy ketone (VIII) by reaction with diphenyl diselenide in the presence of N-acetyl-cysteine and sodium borate.Bucherer-Bergs reaction of ketone (VIII) with potassium cyanide and ammonium carbamate produced a mixture of diastereomeric hydantoins (IX).After N-alkylation of the hydantoin ring of (IX) with benzyl bromide,the desired isomer (X) was isolated by preparative HPLC.Finally,alcohol oxidation,with concomitant hydantoin hydrolysis,by treatment with Jones reagent furnished the title compound.