When Indolizine Meets Quinoline: Diversity-Oriented Synthesis of New Polyheterocycles and Their Optical Properties

Fluorescence-based technologies play a pivotal role in various biomedical applications. Here we report an efficient route to a new class of fluorophores, indolizino­[3,2-<i>c</i>]­quinolines, via the oxidative Pictet–Spengler cyclization strategy. The condensation of several 2-methylpyridines with 2-bromo-2′-nitroacetophenone allowed for the rapid assembly of indolizines with a 2-nitrophenyl group at the C2 position. The subsequent reduction of the nitro group under mild conditions followed by oxidative Pictet–Spengler cyclization with various aryl aldehydes in the presence of a catalytic amount of FeCl₃ furnished the indolizino­[3,2-<i>c</i>]­quinolines in good overall yields. We also examined the photophysical properties of this new series of polyheterocyclic compounds. Several indolizino­[3,2-<i>c</i>]­quinolines were found to have unique and desirable optical properties, suggesting that these compounds may be suitable for use as prospective fluorescent probes in aqueous systems

Diastereoselective Total Synthesis of (−)-Galiellalactone

An enantioselective total synthesis of (−)-galiellalactone has been accomplished. The key features of the synthesis involve the highly stereoselective construction of the <i>cis</i>-trisubstituted cyclopentane intermediate by a Pd(0)-catalyzed cyclization, the stereospecific introduction of an angular hydroxyl group by Riley oxidation, and the efficient construction of the tricyclic system of (−)-galiellalactone via a combination of diastereoselective Hosomi–Sakurai crotylation and ring-closing metathesis (RCM

Food-fodder traits in groundnut

Changes in the level of GPT, BUN, and creatinine by treatment with LL28 in mice. (PDF 109 kb

Stereoselective Synthesis of 7-<i>epi</i>-Incarvilline

The enantioselective synthesis of 7-<i>epi</i>-incarvilline for formal syntheses of (−)-incarvilline, (+)-incarvine C, and (−)-incarvillateine is described. The key features of our synthesis involve (1) stereoselective construction of the optically active bicyclic lactone utilizing Pd(0)-catalyzed allylic alkylation, (2) efficient transformation of the bridged bicyclic lactone to the key bicyclic lactam skeleton, and (3) stereoselective elaborations of two stereocenters via a substrate-controlled catalytic hydrogenation and a 1,4-addition

Additional file 5: Table S4. of Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

Changes in the level of GPT, BUN, and creatinine by treatment with LL28 in mice. (PDF 109 kb

Additional file 3: Table S2. of Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

The IC50 values showing the inhibitory effect of LL28 on the viability of a panel of human lung cancer cells. (PDF 177 kb

Additional file 4: Table S3. of Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

The IC50 values showing the inhibitory effect of LL28 on the anchorage-dependent colony -forming ability of a panel of human lung cancer cells. (PDF 176 kb

Asymmetric Total Synthesis of (+)-Intricenyne via an Endocyclization Route to Oxocane Skeleton

The first total synthesis of (+)-intricenyne consisting of an oxocane skeleton was achieved via an extremely selective endocyclization strategy. The key features of the synthesis include a regio- and diastereoselective epoxide opening reaction, concise elaboration of oxocane cores via abnormally selective endocyclization ether ring formation, and versatile incorporation of the labile functional groups

Asymmetric Total Synthesis of (+)-(3<i>E</i>)‑Pinnatifidenyne via Abnormally Regioselective Pd(0)-Catalyzed Endocyclization

The asymmetric total synthesis of the marine natural product (+)-(3<i>E</i>)-pinnatifidenyne was accomplished. The key features of the synthesis involve the construction of an eight-membered cyclic ether by the abnormally regioselective Pd(0)-catalyzed cyclization, the installation of a double bond in the oxocene skeleton by sequential <i>in situ</i> deconjugative isomerization, and the efficient introduction of the crucial chloride mediated by the substrate-controlled diastereoselective reduction

Discovery of 2‑((<i>R</i>)‑4-(2-Fluoro-4-(methylsulfonyl)phenyl)-2-methylpiperazin-1-yl)‑<i>N</i>‑((1<i>R</i>,2<i>s</i>,3<i>S</i>,5<i>S</i>,7<i>S</i>)‑5-hydroxyadamantan-2-yl)pyrimidine-4-carboxamide (SKI2852): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)

A series of picolinamide- and pyrimidine-4-carboxamide-based inhibitors of 11β-hydroxysteroid dehydrogenase type 1 was synthesized and evaluated to optimize the lead compound <b>9</b>. The combination of the replacement of a pyridine ring of <b>9</b> with a pyrimidine ring and the introduction of an additional fluorine substituent at the 2-position of the phenyl ring resulted in the discovery of a potent, selective, and orally bioavailable inhibitor, <b>18a</b> (SKI2852), which demonstrated no CYP and PXR liabilities, excellent PK profiles across species, and highly potent and sustainable PD activity. Repeated oral administration of <b>18a</b> significantly reduced blood glucose and HbA1c levels and improved the lipid profiles in <i>ob</i>/<i>ob</i> mice. Moreover, the HbA1c-lowering effect of metformin was synergistically enhanced in combination with <b>18a</b>