合成路线1

The tricyclic sulfone intermediate (XVI) has also been obtained as follows: The Diels-Alder condensation between 4,5,6,7-tetrahydroisobenzofuran (XX) and 5(R)-methylfuran-2(5H)-one (XXI) catalyzed by LiClO4 in ethyl ether gives the unsaturated tricyclic epoxyketone (XXII), which is hydrogenated with H2 over Pd/C in ethanol yielding the corresponding saturated epoxylactone (XXIII). Opening of the epoxide ring of (XXIII) by means of lithium hexamethyldisylazane (LiHMDS) in THF affords the hydroxyketone (XXIV), which is isomerized to (XXV) by means of DBU in hot toluene. The hydrogenation of the double bond of (XXV) with H2 over PtO2 in ethanol gives the saturated hydroxylactone (XXVI) with the correct stereochemical configuration. The reduction of the lactone group of (XXVI) with DIBAL, followed by methylation with BF3/Et2O and methanol affords the cyclic hemiketal (XXVII), which is oxidized at the secondary hydroxyl group with Dess-Martin oxidant to give the tricyclic ketone (XXVIII). The reaction of (XXVIII) with methyltriphenylphosphonium iodide and sodium hexamethyldisilazane (NaHMDS) in ethyl ether yields the corresponding methylene derivative (XXIX), which is hydroxylated with BH3/THF and H2O2/NaOH to provide the expected hydroxymethyl derivative (XXX). The reaction of (XXX) with Ms-Cl and triethylamine in dichloromethane gives the mesylate (XXXI), which is condensed with thiophenol and potassium tert-butoxide in DMSO to yield the previously described phenylsulfanyl intermediate (XV), which is finally oxidized with MCPBA as before to the target tricyclic sulfone intermediate (XVI).