Nerve Growth Factor-Potentiating Benzofuran Derivatives from the Medicinal Fungus <i>Phellinus ribis</i>

Four new benzofuran derivatives, ribisin A (<b>1</b>), ribisin B (<b>2</b>), ribisin C (<b>3</b>), and ribisin D (<b>4</b>), were isolated from the MeOH extract of the fruiting bodies of <i>Phellinus ribis.</i> Their structures including their absolute configurations were determined by NMR and CD exciton chirality methods. Compounds <b>1</b>–<b>4</b> were found to promote neurite outgrowth in NGF-mediated PC12 cells at concentrations ranging from 1 to 30 μM. The structure–activity relationships of these compounds are also discussed

Spirocyclic Nortriterpenoids with NGF-Potentiating Activity from the Fruits of <i>Leonurus heterophyllus</i>

Four new spirocyclic nortriterpenoids, leonurusoleanolide A (<b>1</b>), leonurusoleanolide B (<b>2</b>), leonurusoleanolide C (<b>3</b>), and leonurusoleanolide D (<b>4</b>), were isolated from the MeOH extract of the fruits of <i>Leonurus heterophyllus.</i> Compounds <b>1</b> and <b>2</b>, and compounds <b>3</b> and <b>4</b>, were found to exist as equilibrium mixtures of <i>trans</i> and <i>cis</i> isomers. Mixtures of <b>1</b> and <b>2</b>, and <b>3</b> and <b>4</b>, significantly enhanced the neurite outgrowth of nerve growth factor-treated PC12 cells at concentrations ranging from 1 to 30 μM. Compound <b>8</b> was also found to have a neurite outgrowth-promoting effect at concentrations of 1 and 10 μM. The structure–activity relationship of these compounds is discussed

Construction of Successive Chiral Centers Adjacent to a Chiral Tetraalkylated Quaternary Center Using an Asymmetric Aldol Reaction

The aldol reaction of <b>2</b>″ with a variety of different aldehydes gave the corresponding β-lactones <b>4</b> bearing successive asymmetric centers adjacent to a chiral tetraalkylated quaternary center or the (<i>E</i>)-alkenes <b>8</b>. The use of electronically neutral or electron-deficient aldehydes led to <b>4</b> in excellent yields with high diastereoselectivities, whereas electron-rich aldehydes performed poorly and underwent decarboxylation to afford <b>8</b>

Systematic Asymmetric Synthesis of All Diastereomers of (−)-Talaumidin and Their Neurotrophic Activity

(−)-Talaumidin (<b>1</b>), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan isolated from <i>Aristolochia arcuata</i> Masters, shows significant neurite-outgrowth promotion and neuroprotection in primary cultured rat cortical neurons and in NGF-differentiated PC12 cells. The four stereogenic centers on the tetrahydrofuran moiety in <b>1</b> result in the presence of seven diastereomers except for their enantiomers. In order to investigate the stereochemistry–activity relationships of the stereoisomers, the systematic synthesis of all stereoisomers of <b>1</b> was accomplished by employing Evans aldol, diastereoselective hydroboration, reductive deoxygenation, and Mitsunobu reactions as key steps. The ability of all of the synthesized stereoisomers to promote neurite-outgrowth in PC12 and neuronal cells was evaluated. All stereoisomers exhibited moderate to potent neurotrophic activities in NGF-differentiated PC12 cells at 30 μM and in primary cultured rat cortical neuronal cells at 0.01 μM. In particular, <b>1e</b> bearing all <i>cis</i> substituents resulted in the most potent neurite-outgrowth promotion

Tetranorsesquiterpenoids and Santalane-Type Sesquiterpenoids from <i>Illicium lanceolatum</i> and Their Antimicrobial Activity against the Oral Pathogen <i>Porphyromonas gingivalis</i>

The methanol extract of the leaves of <i>Illicium lanceolatum</i>, indigenous to Fujian Province, People’s Republic of China, was found to exhibit antimicrobial activity against the periodontal pathogen <i>Porphyromonas gingivalis</i>, and a bioassay-guided fractionation led to the isolation of two new compounds, <b>1</b> and <b>2</b>, along with two known santalane-type sesquiterpenoids, <b>3</b> and <b>4</b>. The structures of lanceolactone A (<b>1</b>) and lanceolactone B (<b>2</b>) were elucidated by analyzing their 2D NMR spectroscopic data. Compounds <b>1</b> and <b>2</b> were assigned as new tetranorsesquiterpenoids with a spiroacetal ring and tricyclic structure, respectively. Compound <b>3</b> (α-santal-11-en-10-one) showed potent antimicrobial activity against the oral pathogen <i>P. gingivalis</i>

Evaluation of Constituents of <i>Piper retrofractum</i> Fruits on Neurotrophic Activity

Three new compounds, <b>1</b>–<b>3</b>, together with 22 known compounds, were isolated from the fruits of <i>Piper retrofractum</i>. The structures of the new compounds were elucidated on the basis of spectroscopic data analysis and comparison with literature values. Compound <b>1</b> was found to enhance the neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 0.1 to 10 μM

Sucupiranins A–L, Furanocassane Diterpenoids from the Seeds of <i>Bowdichia virgilioides</i>

Twelve new furanocassane diterpenoids, sucupiranins A–L (<b>1</b>–<b>12</b>), and three known compounds (<b>13</b>–<b>15</b>) were isolated from the seeds of <i>Bowdichia virgilioides</i>. The structures of the compounds were elucidated via ¹H and ¹³C NMR analysis, including 2D NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY); HRMS data; and X-ray crystallographic analysis. The absolute configurations were defined using their electronic circular dichroism (ECD) spectra by applying the exciton chirality method to the bis-<i>p</i>-bromobenzoate of compound <b>13</b>. Sucupiranin J (<b>10</b>) inhibited lipopolysaccharide-induced nitric oxide production (IC₅₀ 30.6 μM), whereas sucupiranins J (<b>10</b>), K (<b>11</b>), and <b>13</b> exhibited weak antimalarial activity against <i>Plasmodium falciparum</i> K1 with IC₅₀ values of 32.2, 23.5, and 22.9 μM and selectivity indices of 4.3, 1.9, and >12.0 (MRC-5/K1), respectively

Sucupiranins A–L, Furanocassane Diterpenoids from the Seeds of <i>Bowdichia virgilioides</i>

Twelve new furanocassane diterpenoids, sucupiranins A–L (<b>1</b>–<b>12</b>), and three known compounds (<b>13</b>–<b>15</b>) were isolated from the seeds of <i>Bowdichia virgilioides</i>. The structures of the compounds were elucidated via ¹H and ¹³C NMR analysis, including 2D NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY); HRMS data; and X-ray crystallographic analysis. The absolute configurations were defined using their electronic circular dichroism (ECD) spectra by applying the exciton chirality method to the bis-<i>p</i>-bromobenzoate of compound <b>13</b>. Sucupiranin J (<b>10</b>) inhibited lipopolysaccharide-induced nitric oxide production (IC₅₀ 30.6 μM), whereas sucupiranins J (<b>10</b>), K (<b>11</b>), and <b>13</b> exhibited weak antimalarial activity against <i>Plasmodium falciparum</i> K1 with IC₅₀ values of 32.2, 23.5, and 22.9 μM and selectivity indices of 4.3, 1.9, and >12.0 (MRC-5/K1), respectively