合成路线1

Lactone acid (VI) is amidated with N-methylhex-5-enamine (VII) in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HATU) and DIEA in DMF at 0 °C. The resulting lactone amide (VIII) is opened with LiOH in THF/methanol/H2O and the intermediate carboxylic acid is then condensed with the hydrochloride of amine (IX) by means of DIAD and HATU in DMF, producing hydroxyamide (X) . Finally, alcohol (X) and quinolinol derivative (XI) are coupled under Mitsunobu conditions (PPh3, DIAD) in THF .
Alternatively, lactone acid (VI) is esterified with di-tert-butyl dicarbonate (Boc2O) in the presence of DMAP in CH2Cl2, providing the tert-butyl-protected lactone (XII), which is then opened by treatment with LiOH in dioxane/H2O at 0 °C. Amidation of the in situ-generated acid with the vinylcyclopropyl amino acid ester (IX) (in its hydrochloride form) in DMF at 0 °C gives amino acid (XIII), which is coupled with the quinoline moiety (XI) by a Mitsunobu reaction (PPh3, DIAD) in THF at 0 °C, affording adduct (XIV), with the proper configuration of the chiral center at position 3 of the cyclopentane. Subsequent deprotection of the tert-butyl ester (XIV) with triethylsilane and TFA in CH2Cl2 followed by condensation of the resulting acid with alkenylamine (VII) by means of DIAD and HATU in DMF at 0 °C yields the desired noncyclic diene (I) .