合成路线1

Hydrogenation of D-4-hydroxyphenyl glycine (I) over Raney-Ni in NaOH affords 4-hydroxycyclohexylglycine (II), which is condensed with sulfonyl chloride (III) in dioxane in the presence of Et3N to yield derivative (IV). Carboxylic acid (IV) is converted into benzyl ester (VI) by treatment with benzyl bromide (V) by means of N,N'-dicyclohexylamine (DCHA) in DMF and (VI) is then oxidized by treatment with NaBr, 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO) and NaClO2 in CH2Cl2/H2O to provide ketone (VII). Condensation of (VII) with n-propanol (VIII) by means of PhSiH3 and TFA gives a mixture of compounds from which trans-(IX) is cromatographically separated. Then ketone (IX) reacts with 4-picolyl chloride (X) and K2CO3 in DMF to furnish compound (XI). Hydrogenation of benzyl acetate (XI) over Pd/C in EtOH/HCl affords acetic acid derivative (XII), which is coupled to O-t-butylhydroxylamine hydrochloride by means of HOBt, N-methylmorpholine and N-[dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride (EDC·HCl) in CH2Cl2. Finally, removal of the t-Bu group with HCl (gas) in dichloroethane/EtOH yields the desired compound.