合成路线1

Treatment of 1,2,4-butanetriol (I) with acetone and p-toluenesulfonic acid gave the isopropylidene ketal (II). Subsequent Swern oxidation of the unprotected alcohol group of (II) produced aldehyde (III), which was condensed with phosphorane (IV) to afford unsaturated ester (V). Ketal hydrolysis of (V) gave ethyl 5,6-dihydroxy-2-hexenoate (VI), which was cyclized by means of iodine and NaHCO3 to produce the (tetrahydrofuranyl)-2-iodoacetate (VII). Further oxidation of the hydroxyl group of (VII) by means of Jones reagent yielded iodoketone (VIII). This was cyclized in the presence of DBU to generate the bicyclic compound (IX). The Bucherer-Bergs reac-tion of (IX) with potassium cyanide and ammonium carbonate produced the spiro hydantoin (X). Resolution of (X) was then achieved by ethyl ester hydrolysis, followed by recrystallization of the corresponding diastereomeric salt with (R)-2-phenylglycinol. Basic hydrolysis of the hydantoin ring of the required isomer (XII) then yielded the title compound.