合成路线1

The oxidation of N-(benzyloxycarbonyl)-L-phenylalaninol (I) with oxalyl chloride in DMSO gives the corresponding aldehyde (II), which by dimerization with Zn dust in dichloromethane yields (2S,3R,4R,5S)-2,5-bis(benzyloxycarbonylamino)-1,6-diphenylhexane-3,4-diol (III) [along with the (2S,3S,4S,5S)-isomer]. The reaction of (III) with alpha-acetoxyisobutyryl bromide (IV) in hexane/dichloromethane affords (2S,3R,4R,5S)-2,5-bis(benzyloxycarbonylamino)-4-bromo-1,6-diphenylhexan-3-ol acetate ester (V), which is converted into the corresponding epoxide (VI) with NaOH in dioxane/water. The reduction of the epoxide (VI) with NaBH4 in THF affords (2S,3S,5S)-2,5-bis(benzyloxycarbonylamino)-1,6-diphenylhexan-3-ol (VII), which is deprotected with Ba(OH)2 in refluxing dioxane/water yielding the corresponding diamine (VIII). The cyclization of (VIII) with phenylboronic acid (IX) in refluxing toluene gives (4S,6S)-6-[1(S)-amino-2-phenylethyl]-4-benzyl-2-phenyl-1,3,2-oxaazaborinane (X), which is condensed with (5-thiazolylmethyl)(4-nitrophenyl)carbonate (XI) in THF to afford (2S,3S,5S)-5-amino-1,6-diphenyl-2-(5-thiazolylmethoxycarbonylamino) hexan-3-ol (XII). Finally, this compound is condensed with N-[N-(2-isopropylthiazol-4-ylmethyl)-N-methylaminocarbonyl]-L-valine (XIII) by means of 1-hydroxybenzotriazole (HBT) and N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide (DEC) in THF.