合成路线1

Aldol condensation between (S)-2-(benzyloxy)-3-methylbutanal (XI) and thioacetal (XII) by means of LDA, tert-butyldimethylsilyl chloride and tin tetrachloride in THF/HMPA gives syn diastereomer (XIII), which is then reduced with LiAlH4 in ether to provide diol (XIV). Protection of the primary hydroxyl group of (XIV) with tert-butyldimethylsilyl chloride in the presence of DMAP and Et3N, followed by reaction with chloride (XV) and DIEA in CH2Cl2, affords protected derivative (XVI), whose benzyl group is then removed by treatment with Na/NH3. The resulting alcohol (XVII) is acetylated with acetic anhydride in CH2Cl2 in the presence of DMAP to give acetate (XVIII). Treatment of D-alloisoleucine (XX) with N-[[(benzyloxy)carbonyl]oxy]-5-norbornene-2,3-dicarboximide and Et3N in THF/H2O, followed by reaction with 1,1'-carbonyldiimidazole (CDI), provides the corresponding imidazolide (XIX), which is then condensed with derivative (XVIII) to yield beta-keto ester (XXI). Reduction of (XXI) with KBH4 in EtOH, followed by protection with triiospropylsilyl triflate, affords a mixture of two diastereomers from which compound (XXII) is cromatographically isolated. Removal of the carbobenzyloxy group of (XXII) by hydrogenation over Pd/C gives amino derivative (XXIII), which is then coupled to intermediate (VIII) by means of isopropenyl chloroformate and NMM in THF to furnish linear peptide (XXIV).