合成路线1

Alkylation of ethyl nipecotate (I) with ethyl bromoacetate gave diester (II). Subsequent Dieckmann cyclization of (II) with t-BuOK, followed by acid decarboxylation afforded azabicyclo[3.2.1]octane-6-one (III). Knoevenagel condensation of (III) with ethyl cyanoacetate afforded unsaturated cyano ester (IV), which was hydrogenated over Pd/C to provide (V). Nitrosation of (V) with isoamyl nitrite in the presence of NaOEt gave the hydroxymino nitrile (VI). This was treated with S2Cl2 in cold DMF to generate the thiadiazole (VII). Hydrogenolysis of the 6-chloro of (VII) provided a mixture of isomers, from which the exo compound (VIII) was isolated by column chromatography. The required propyl thioether was then obtained by reaction with sodium hydrosulfide and n-propyl bromide in DMF. Finally, resolution with L-tartaric acid yielded the title (5S,6S) enantiomer.