合成路线1

A new solid phase synthesis of abacavir has been reported: Condensation of the chiral 4(R)-benzyl-3-(4-pentenoyl)oxazolidin-2-thione (I) with acrolein (II) by means of TiCl4 and DIEA gives the adduct (III), which was transformed into the chiral cyclopentene (IV) by catalytic ring-closing metathesis. The reductive removal of the chiral auxiliary with LiBH4 affords the chiral diol (V), which is selectively silylated with TBDMSCl providing the primary silyl ether (VI). Acylation of the secondary alcohol of (VI) with benzoic anhydride gives the benzoate (VII), which is desilylated with HF in acetonitrile yielding the allylic benzoate (VIII). Benzoate (VIII) is condensed with a p-nitrophenyl Wang carbonate resin (IX) by means of DIEA and DMAP affording the solid phase resin (X) which is condensed with 2-amino-6-chloropurine (XI) by means of a Pd catalyst furnishing the adduct (XII). Thermal condensation of (XII) with cyclopropylamine (XIII) yields the diaminopurine resin (XIV) which, after cleavage from the resin by a treatment with TFA in dichloromethane, gives directly abacavir.