TBAI/TBHP-Mediated Cascade Cyclization toward Sulfonylated Indeno[1,2‑<i>c</i>]quinolines

Treatment of <i>ortho</i>-amino-substituted aryldiyne derivatives with sulfonyl hydrazides in the presence of tetrabutylammonium iodide (TBAI) and <i>tert</i>-butyl hydroperoxide (TBHP) led to a cascade cyclization reaction to yield sulfonylated indeno­[1,2-<i>c</i>]­quinolines in moderate to good yields. The features of the methodology include metal-free reaction, the ease of reagent handling, and a broad functional group tolerance

Asymmetric Synthesis of <i>gem</i>-Difluoromethylenated Linear Triquinanes via Cascade <i>gem</i>-Difluoroalkyl Radical Cyclization

An asymmetric synthesis of <i>gem</i>-difluoromethylenated linear triquinanes is described exploiting the synthetic utilities of PhSCF₂TMS (<b>5</b>) as a “^•CF₂^–’’ building block. The strategy involves fluoride-catalyzed nucleophilic addition of PhSCF₂TMS (<b>5</b>) to chiral ketocyclopentenes <b>6</b> to provide silylated adducts <b>9</b> or alcohol derivatives <b>10</b> and <b>11</b>. Subsequent cascade radical cyclization of the <i>gem</i>-difluoroalkyl radical generated from silylated adducts <b>9</b> or alcohols <b>10</b> and <b>11</b> afforded <i>gem</i>-difluoromethylenated linear triquinanes <b>16</b> as an approximate 1:1 mixture of two diastereomers (<b>16A</b> and <b>16B</b>). Alternatively, a convenient asymmetric synthesis of <i>gem</i>-difluoromethylenated linear triquinanes <b>16A</b> can be accomplished by oxidation of <b>16a</b> (R = H) to provide ketotriquinane <b>17</b> followed by a highly stereoselective nucleophilic addition to <b>17</b> employing DIBAL, NaBH₄, and various Grignard reagents

Synthesis of <i>gem</i>-Difluoromethylenated Polycyclic Cage Compounds

The synthesis of <i>gem</i>-difluoromethylenated polycyclic cage compounds, utilizing PhSCF₂SiMe₃ as a <i>gem</i>-difluoromethylene building block, is described. The fluoride-catalyzed nucleophilic addition of PhSCF₂SiMe₃ to both maleic anhydride–cyclopentadiene and maleic anhydride–cyclohexadiene adducts was accomplished with high stereoselectivity to provide the corresponding adducts that were treated with Grignard reagents, followed by acid-catalyzed lactonization to afford the corresponding γ-butyrolactones, each as a single isomer. These γ-butyrolactones underwent intramolecular radical cyclization to give the corresponding tetracyclic cage γ-butyrolactones, which were employed as precursors for the synthesis of <i>gem</i>-difluoromethylenated tetracyclic cage lactols or tetracyclic cage furans, upon treatment with Grignard reagents

Asymmetric Synthesis of <i>gem</i>-Difluoromethylenated Linear Triquinanes via Cascade <i>gem</i>-Difluoroalkyl Radical Cyclization

An asymmetric synthesis of <i>gem</i>-difluoromethylenated linear triquinanes is described exploiting the synthetic utilities of PhSCF₂TMS (<b>5</b>) as a “^•CF₂^–’’ building block. The strategy involves fluoride-catalyzed nucleophilic addition of PhSCF₂TMS (<b>5</b>) to chiral ketocyclopentenes <b>6</b> to provide silylated adducts <b>9</b> or alcohol derivatives <b>10</b> and <b>11</b>. Subsequent cascade radical cyclization of the <i>gem</i>-difluoroalkyl radical generated from silylated adducts <b>9</b> or alcohols <b>10</b> and <b>11</b> afforded <i>gem</i>-difluoromethylenated linear triquinanes <b>16</b> as an approximate 1:1 mixture of two diastereomers (<b>16A</b> and <b>16B</b>). Alternatively, a convenient asymmetric synthesis of <i>gem</i>-difluoromethylenated linear triquinanes <b>16A</b> can be accomplished by oxidation of <b>16a</b> (R = H) to provide ketotriquinane <b>17</b> followed by a highly stereoselective nucleophilic addition to <b>17</b> employing DIBAL, NaBH₄, and various Grignard reagents

Synthesis of <i>gem</i>-Difluoromethylenated Polycyclic Cage Compounds

The synthesis of <i>gem</i>-difluoromethylenated polycyclic cage compounds, utilizing PhSCF₂SiMe₃ as a <i>gem</i>-difluoromethylene building block, is described. The fluoride-catalyzed nucleophilic addition of PhSCF₂SiMe₃ to both maleic anhydride–cyclopentadiene and maleic anhydride–cyclohexadiene adducts was accomplished with high stereoselectivity to provide the corresponding adducts that were treated with Grignard reagents, followed by acid-catalyzed lactonization to afford the corresponding γ-butyrolactones, each as a single isomer. These γ-butyrolactones underwent intramolecular radical cyclization to give the corresponding tetracyclic cage γ-butyrolactones, which were employed as precursors for the synthesis of <i>gem</i>-difluoromethylenated tetracyclic cage lactols or tetracyclic cage furans, upon treatment with Grignard reagents

Lovastatin Analogues from the Soil-Derived Fungus <i>Aspergillus sclerotiorum</i> PSU-RSPG178

Three new lovastatin analogues (<b>1</b>, <b>4</b>, and <b>5</b>) together with four known lovastatin derivatives, namely, lovastatin (<b>2</b>), α,β-dehydrolovastatin (<b>3</b>), α,β-dehydrodihydromonacolin K (<b>6</b>), and α,β-dehydro-4a,5-dihydromonacolin L (<b>7</b>), were isolated from the soil-derived fungus <i>Aspergillus sclerotiorum</i> PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound <b>5</b> exhibited the most potent activity against HMG-CoA reductase, with an IC₅₀ value of 387 μM. In addition, the present study indicated the direct interaction of compound <b>5</b> with HMG-CoA reductase. Compound <b>5</b> was considered to be noncytotoxic against noncancerous Vero cells, with an IC₅₀ value of 40.0 μM, whereas compound <b>2</b> displayed much stronger activity, with an IC₅₀ value of 2.2 μM