Oxidation of 2,3-dimethylfuran (I) under Vilsmeier conditions with POCl3 in DMF affords aldehyde (II), which is then condensed with benzothiophene (III) by means of n-BuLi in THF to provide secondary alcohol (IV). Reduction of (IV) under Nutaitis conditions with NaBH4 and TFA in THF yields methylene congener (V), which is then treated with p-anisoyl chloride (VI) under Friedel-Crafts conditions with SnCl4 in CS2 to give 1-oxa-9-thiacyclopenta[b]fluorene heterocycle (VII). Demethylation of methyl ether (VII) with BBr3 in CH2Cl2 affords phenol (VIII), which is then bis-iodinated with molecular iodine and NaOH in MeOH to yield di-iodo phenol (IX). Compound (IX) is then condensed with (S)-2-hydroxy-3-phenylpropionic acid (X) under Mitsunobu conditions with DEAD and PPh3 in benzene to furnish (R)-2-benzyl-acetic acid derivative (XI), which is finally hydrolyzed by treatment with KOH in H2O/dioxane to provide the desired product.

Oxidation of 2,3-dimethylfuran (I) under Vilsmeier conditions with POCl3 in DMF affords aldehyde (II), which is then condensed with benzothiophene (III) by means of n-BuLi in THF to provide secondary alcohol (IV). Reduction of (IV) under Nutaitis conditions with NaBH4 and TFA in THF yields methylene congener (V), which is then treated with p-anisoyl chloride (VI) under Friedel-Crafts conditions with SnCl4 in CS2 to give 1-oxa-9-thiacyclopenta[b]fluorene heterocycle (VII). Demethylation of methyl ether (VII) with BBr3 in CH2Cl2 affords phenol (VIII), which is then bis-iodinated with molecular iodine and NaOH in MeOH to yield di-iodo phenol (IX). Compound (IX) is then condensed with (S)-2-hydroxy-3-phenylpropionic acid (X) under Mitsunobu conditions with DEAD and PPh3 in benzene to furnish (R)-2-benzyl-acetic acid derivative (XI), which is finally hydrolyzed by treatment with KOH in H2O/dioxane to provide the desired product.