合成路线1

Coupling of threonine benzyl ester (I) to Fmoc-Ile-OH (A) with HBTU, HOBt and DIEA in dichloromethane followed by protection of the hydroxyl group with TBDPS-Cl and imidazole in THF affords protected dipeptide (II). Removal of the Fmoc group of (II) with piperidine/DMF followed by coupling of Fmoc-N-Me-Ile-OH (B) with HBTU, HOBt and DIEA gives fully protected tripeptide (III), which is treated with piperidine/DMF for Fmoc removal and acetylated by means of Ac2O, DIEA in dichloromethane to furnish (IV). Debenzylation of (IV) by hydrogenolysis over Pd/C provides intermediate (V). Addition of 2-bromopropene (VII) and t-BuLi to the Boc-leucine Weinreb amide (VI) in Et2O yields alpha',beta'-unsaturated ketone (VIII), which is oxidized by treatment with H2O2 and DIEA in H2O/benzonitrile/MeOH to afford a mixture of epoxides from which (IX) is separated by column chromatography. Boc deprotection and coupling of peptide (V) with intermediate (IX) by means of TFA, HATU, HOAt, DIEA in dichloromethane, furnishes TBDPS-protected derivative (X), which is finally deprotected by treatment with TBAF in THF.