合成路线1

Coupling of 2,5-dimethylphenol (I) with methyl 3,3-dimethylacrylate (II) by means of methanesulfonic acid yields dihydrocoumarin (III), which is reduced with LiAlH4 in THF to provide alcohol (IV). Selective O-protection at the primary hydroxy group of (IV) with tert-butyldimethylsilyl chloride (TBDMS-Cl) and Et3N in dichloromethane affords compound (V), which is then coupled with Boc-Ala-OH (VI) by means of EDC and DMAP in dichloromethane to give ester (VII). O-Deprotection of (VII) with HOAc in THF/H2O furnishes alcohol (VIII), which is then oxidized by means of pyridinium chlorochromate (PCC) in dichloromethane, giving aldehyde (IX). Compound (IX) is further oxidized with NaClO2 and sodium sulfite (Na2CO3) in H2O and NaH2PO4 in acetonitrile to yield propionic acid (X), whose Boc group is removed by treatment with TFA in dichloromethane, furnishing hydrochloride (XI). Coupling of (XI) with PEG thiazolidinethione (T-PEG) (XII) (1) by means of DIEA in dichloromethane gives PEG-alaninyl derivative (XIII), which is finally condensed with daunorubicin hydrochloride (XIV) by means of EDC · HCl, HOBt and NMM in dichloromethane to afford the target product.