合成路线1

Michael addition of bis(trimethylsilyl)phosphonite (II) to benzyl 2-phenethylacrylate (I) afforded phosphinic acid (III). 4-Benzoylbenzyl bromide (IV) was reduced using triethylsilane and trifluoroacetic acid to give 4-benzylbenzyl bromide (V). Subsequent Arbuzov reaction of phosphinic acid (III) with bromide (V) generated the disubstituted phosphinic acid (VI), which was protected as the methyl ester (VII) employing trimethylsilyl diazomethane. Hydrogenolysis of the benzyl ester of (VII) then yielded carboxylic acid (VIII). This was coupled with (S)-tert-leucinamide (IX) by means of BOP to furnish the corresponding diamide (X). Alternatively, acid (VIII) was treated with N-hydroxysuccinimide (NHS) and EDC, and the resulting succinimidyl ester (XI) was coupled with amine (IX) to produce (X). The methyl phosphinate ester (X) was then deprotected by treatment with aqueous trifluoroacetic acid, and the required (S,S)-diastereoisomer was isolated by reverse phase flash chromatography.