Synthesis of 3-arylisocoumarins, including thunberginols A and B, unsymmetrical 3,4-disubstituted isocoumarins, and 3-ylidenephthalides via iodolactonization of methyl 2-ynylbenzoates or the corresponding carboxylic acids

Synthesis of 3-Substituted Isocoumarins and Their Inhibitory Effects on Degranulation of RBL-2H3 Cells Induced by Antigen

“…In contrast, treatment of 4i with BBr 3 under similar conditions gave the partially deprotected 6-methylated thunberginol B (1e, entry 3, 97% yield). Despite the report of complete demethylation of 4i using BBr 3 (10 eq) at rt by Rossi et al,9) in our hands, 1b was obtained in low yields, along with some decomposition compounds, only after treatment of 4i with excess BBr 3 (10 eq) in refluxing 1,1,2,2-tetrachloroethane.To improve the yield of 1b, our synthetic methodology was modified using 4-MOM-protected d-ketoamide 3k (Table 1, entry 11) as the precursor (Chart 1). The two-step isocoumarin synthesis, as described above, was applied to amide 2d (Table 1, entry 11) to afford 6-deprotected isocoumarin 4k (79% overall yield from 2d).…”

“…In contrast, treatment of 4i with BBr 3 under similar conditions gave the partially deprotected 6-methylated thunberginol B (1e, entry 3, 97% yield). Despite the report of complete demethylation of 4i using BBr 3 (10 eq) at rt by Rossi et al,9) in our hands, 1b was obtained in low yields, along with some decomposition compounds, only after treatment of 4i with excess BBr 3 (10 eq) in refluxing 1,1,2,2-tetrachloroethane.…”

Synthesis of Heterocycles and Carbocycles by Electrophilic Cyclization of Alkynes

“…Treatment with aryl halides and a Pd catalyst affords predominantly aryl-substituted phthalides [54]. Halolactonization by N-halosuccinimides in the presence of NaHCO 3 and Triton-B in CH 2 Cl 2 [56] or I 2 plus NaHCO 3 in MeCN [57] is reported to produce good yields of the corresponding 4-haloisocoumarins. The corresponding methyl esters have also been cyclized to isocoumarins in good yields by use of HI A number of different heterocycles have been obtained by cyclization of acetylenic amides.…”

Synthesis and anti-inflammatory activity of fluorinated isocoumarins and 3,4-dihydroisocoumarins

“…The isocoumarin nucleus is an abundant structural motif in natural products [2]. Many constituents of the steadily growing class of known isocoumarins exhibit valuable biological properties such as antifungal [3,4], antitumor or cytotoxic [5][6][7], antiinflammatory, anti-allergic and enzyme inhibitory activity [8]. Naturally occurring isocoumarins containing halogens have been seldom reported, examples of naturally occurring isocoumarins containing fluorine are not known yet.…”