合成路线1

The reaction of N,N-dibenzyl-L-alaninal (I) with nitromethane, catalyzed by the chiral ammonium salt (II) and KF in THF gives the chiral nitroalcohol (III), which is reduced with NiCl2 and NaBH4 to yield the aminoalcohol (IV). The condensation of (IV) with isobutyraldehyde (V) affords the Schiff base (VI), which is reduced with NaBH4 to provide the secondary amine (VII). The reaction of (VII) with 4-nitrobenzenesulfonyl chloride (VIII) and TEA in dichloromethane furnishes the sulfonamide (IX), which is deprotected by hydrogenation with H2 over Pd/C in methanol, giving the diamino compound (X). Finally, this compound is condensed with 3(S)-tetrahydrofuryl (N-oxysuccinimidyl) carbonate (XI) by means of TEA in dichloromethane to afford the target carbamate.

合成路线2

The reaction of butadiene monooxide (XI) with phenylmagnesium bromide (XII) and CuCN in THF gives trans-4-phenyl-2-buten-1-ol (XIII), which is enantioselectively epoxidated with Ti(O-iPr)4, diethyl D-tartrate and tBu-OOH to yield the (2R,3R)-epoxide (XIV). The reaction of (XIV) with Ti(O-iPr)4 and N3-SiMe3 in refluxing benzene affords the chiral azidodiol (XV), which is epoxidated by means of 2-acetoxyisobutyryl chloride (AcBCl) and NaOMe in THF to provide the chiral azidoepoxide (XVI) (1). Opening of the epoxide ring of (XVI) with isobutylamine (XVII) in hot isopropanol gives the secondary amine (XVIII), which is acylated with 4-aminophenylsulfonyl chloride (XIX) and pyridine in dichloromethane to yield the corresponding sulfonamide (XX). The reduction of the azido group of (XX) with H2 over Pd/C in THF/methanol/HOAc affords the expected primary amine (XXI), which is finally condensed with the already reported intermediate (X) in dichloromethane to provide the target carbamate.

合成路线3