合成路线1

The Grignard reagent (II), prepared from 6-(benzyloxy)hexyl bromide (I), was condensed with 3-chlorofluoren-9-one (III) to give the carbinol (IV). Hydrogenolysis of (IV) over Pd/C gave fluorenylhexanol (V), which was oxidized to the corresponding aldehyde (VI) under Swern conditions using oxalyl chloride and DMSO. Oxime (VII) was then prepared by reaction of (VI) with hydroxylamine. Treatment of (VII) with NaOCl and Et3N generated an intermediate nitrile oxide which, in the presence of dimethyl itaconate (VIII), experienced a [3+2] cycloaddition to afford the isoxazole (IX). Reductive opening of this heterocycle by hydrogenation in the presence of Raney Nickel and boric acid produced the hydroxyketone (X), and further reduction of (X) using NaHB(OAc)3 in AcOH yielded dihydroxyester (XI) as a mixture of diastereoisomers. Saponification with NaOH, followed by recrystallization of the resulting disodium salt, then furnished the racemic mixture of (3R*,5S*,9R*)- and (3R*,5S*,9S*)-diastereoisomers (XII).