合成路线1

Synthesis of 261501: The optical resolution of trans-3-penten-2-ol (IX) with porcine pancreatic lipase (PPL) and trifluoroethyl laurate in ethyl ether gives the (S)-trans-isomer (X), which is condensed with propargyl alcohol (XI) by means of tetrabutylammonium hyrogensulfate and NaOH in water, yielding the corresponding ether (XII). Rearrangement of (XII) by means of BuLi in THF affords (3R,4R,5E)-4-methylhept-5-en-1-yn-3-ol (XIII), which is silylated with Tbdms-Cl and imidazole to afford the corresponding silyl ether (XIV). The reaction of (XIV) with BH3 in THF provides the aldehyde (XV), which is condensed with phosphonate (XVI) by means of tetramethylguanidine (TMG) in THF to give the nonadienoic ester (XVII). Ozonolysis of (XVII), followed by reaction with Zn/HOAc yields the aldehyde (XVIII), which is condensed with benzyltriphenylphosphonium chloride (XIX) by means of BuLi in THF to afford the 8-phenyloctadienoic ester (XX). The hydrolysis of (XX) with LiOH in acetone/water furnishes the corresponding free acid (XXI), which is condensed with 3-chloro-4-methoxy-L-phenylalanine trichloroethyl ester (XXII) by means of pentafluorodiphenylphosphinate (FDPP) and DIEA in DMF to give the corresponding amide (XXIII). The desilylation of (XXIII) with aqueous HF in acetonitrile affords the hydroxyamide (XXIV), which is esterified with the intermediate 2(S)-[3-(tert-butoxycarbonylamino)-2,2-dimethylpropionyloxy]-4-methylpentanoic acid (VIII) by means of DCC and DMAP in dichloromethane gives the corresponding ester (XXV).