Dihydroisocoumarins. IV. Reaction with N-Bromosuccinimide. A New Route to Some Isocoumarin Syntheses

Synthesis and 5-HT2A Antagonist Activity of Derivatives of the Novel Heterocycles Indolo[3,2-d]pyrrolo[3,2-g]azecine and Benzo[d]pyrrolo[3,2-g]azecine compared to the Benz[d]indolo[2,3-g]azecine Derivative LE 300

“…Furthermore, synthesis of the benzene analogues, namely benzopyrroloquinolizine 17 and benzopyrroloazecine 19 was carried out as outlined in Scheme 3. Thus, the amine 8 was allowed to react with isochromanone [16] 15 to yield the intermediate amide 16. Sequential cyclization of 16 with phosphorus oxychloride, followed by reduction with sodium borohydride, quaternization with methyl iodide and reductive cleavage with sodium in liquid ammonia yielded the desired compound 19.…”

“…IR (NaCl): ν (cm 1 ) a band split at 3400 and 2925 (NH, CH), 1460 (aromatics). 1 (16) A mixture of isochromanone 15 (3.7 g, 25 mmol) and the amine 8 (3.7 g, 30 mmol), in toluene (30 mL) was heated under reflux for 48 h. After cooling to room temperature, all the toluene was evaporated under reduced pressure and the remaining dark sticky mass was triturated with ethanol (5 mL) and allowed to stay 2 d in the refrigerator. The formed crystals were filtered, washed with cold ethanol and finally crystallized twice from ethanol as creamy white needles, mp 106-108 °C; yield 2.4 g (35%).…”

Boosting Molecular Complexity with O2: Iron‐Catalysed Oxygenation of 1‐Arylisochromans through Dehydrogenation, Csp3−O Bond Cleavage and Hydrogenolysis

“…A case in point is the oxidation of isochroman and its derivatives, which can lead to products of widely ranging bioactivities but has generally been performed with toxic, expensive and/or environmentally hazardous terminal oxidants, such as CrO 3 /H 2 SO 4 , 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), ceric ammonium nitrate (CAN), SeO 2 , CrO 3 /H 5 IO 6 and KMnO 4 . Of particular note is the oxidative cleavage of the endocyclic Csp 3 −O bond in 1‐arylisochromans, which has been exploited by medicinal chemists for the synthesis of benzodiazepines, benzodiazepinones and benzodiazepinethiones, analogues of the neuroprotective agent GYKI52466 and the related LY300164 and tofisopam (Scheme A) .…”

“…[7] However,t he development of similarc atalysts for the selective aerobic oxidation of ethers, particularly the oxidative cleavage of ethereal CÀOb onds, has received much less attention, [7c, 8] although such reactions could provide new pathways for the synthesis of bioactive molecules and new insight into the mechanisms of ether degradation by oxygenases and drug metabolism. [9] Acase in point is the oxidation of isochroman andits derivatives, which can lead to products of widely ranging bioactivities but has generally been performedw ith toxic, expensive and/or environmentally hazardous terminal oxidants, [10,11] such as CrO 3 /H 2 SO 4 , [12] 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), [13] ceric ammonium nitrate (CAN), [14] SeO 2 , [15] CrO 3 / H 5 IO 6 [16] and KMnO 4 . [17] Of particularn ote is the oxidative cleavage of the endocyclic Csp 3 ÀOb ond in 1-arylisochromans, which has been exploited by medicinal chemists fort he synthesis of benzodiazepines, benzodiazepinones and benzodiazepinethiones, analogues of the neuroprotective agent GYKI52466 and the related LY300164 and tofisopam (Scheme 1A).…”

A Single-Step Synthesis of Xyridins A and B, Metabolites from Xyris indica

“…In the literature unsubstituted 4,5-, 6,7-methylenedioxyisocoumarins and 4,5-, 5,6-, 6,7-methylenedioxy-3,4-dihydroisocoumarins are known along with 3-methyl-6,7-methylenedioxy-3,4-dihydroisocoumarin as the only example of a 3-alkyl-substituted 6,7-methylenedioxyisocoumarin [2][3][4]. Some important examples of other natural products bearing a 6,7-methylenedioxydihydroisocoumarin moiety are hippeastrine [5], tetrabenzylcorricidin [6], lycoricidin [7], pancratistatin [8,9], and tazettine [10].…”