Ir-Catalyzed Enantioselective, Intramolecular Silylation of Methyl C–H Bonds

We report highly enantio­selective intramolecular, silylations of unactivated, primary C­(sp³)–H bonds. The reactions form dihydro­benzo­siloles in high yields with excellent enantio­selectivities by functionalization of enantio­topic methyl groups under mild conditions. The reaction is catalyzed by an iridium complex generated from [Ir­(COD)­OMe]₂ and chiral dinitrogen ligands that we recently disclosed. The C–Si bonds in the enantio­enriched dihydro­benzo­siloles were further transformed to C–Cl, C–Br, C–I, and C–O bonds in final products. The potential of this reaction was illustrated by sequential C­(sp³)–H and C­(sp²)–H silylations and functionalizations, as well as diastereo­selective C–H silylations of a chiral, natural-product derivative containing multiple types of C–H bonds. Preliminary mechanistic studies suggest that C–H cleavage is the rate-determining step

Enantioselective Approach to 13a-Methylphenanthroindolizidine Alkaloids

The first enantioselective approach to 13a-methylphenanthroindolizidine alkaloids is reported, featuring an efficient stereoselective Seebach’s alkylation and Pictet–Spengler cyclization. The proposed and other three most probable structures were ruled out, indicating hypoestestatin 1 needs further assignment

An Enantioselective Strategy for the Synthesis of (<i>S</i>)‑Tylophorine via One-Pot Intramolecular Schmidt/Bischler–Napieralski/Imine-Reduction Cascade Sequence

A novel enantioselective strategy for the total synthesis of (<i>S</i>)-tylophorine was developed in an overall yield of 48% with more than 99% ee from readily avaliable azido acid and phenanthryl alcohol. This route features an Evans stereoselective alkylation and an unprecedented one-pot intramolecular Schmidt/Bischler–Napieralski/imine-reduction cascade sequence, in which three new bonds and two rings formed in 84% yield. The intramolecular Schmidt rearrangement of the azido aldehyde was proved to be racemization-free

Bioinspired Construction of a Spirocyclohexadienone Moiety via Sodium Nitrite Catalyzed Aerobic Intramolecular Oxidative Phenol Coupling

An efficient and green intramolecular oxidative phenol coupling for the direct construction of spirocyclohexadienones has been developed, which uses environment-friendly sodium nitrite as the catalyst and oxygen in the air as the terminal oxidant. Hydroxy-containing substituted phenanthrenes and dibenzoazepines could be easily obtained from the dienone–phenol rearrangement

Design, Synthesis, Antiviral Activity, and Structure–Activity Relationships (SARs) of Two Types of Structurally Novel Phenanthroindo/quinolizidine Analogues

To investigate the influence of the variation of the original skeletons of natural phenanthroindo/quinolizidine alkaloids on antiviral activities, two types of structurally totally novel analogues <b>7a</b>, <b>7b</b>, <b>16a</b>, and <b>16b</b> were designed, synthesized, and evaluated against tobacco mosaic virus (TMV) for the first time. Bioassay results indicated that all four of the newly designed analogues showed good to excellent antiviral activities, among which analogue <b>16a</b> dispalyed comparable activity with that of ningnanmycin, perhaps one of the most successful commercial antiviral agents, thus emerging as a potential inhibitor of plant virus and serving as a new lead for further optimization. Further structure–activity relationships are also discussed, demonstrating for the first time that the same changes of the original skeletons of phenanthroindolizidine and phenanthroquinolizidine exihibted totally different antiviral activities results, providing some original and useful information about the preferential conformation for maintaining high activities

Spatial Configuration and Three-Dimensional Conformation Directed Design, Synthesis, Antiviral Activity, and Structure–Activity Relationships of Phenanthroindolizidine Analogues

Our recent investigation on the antiviral activities against tobacco mosaic virus (TMV) of phenanthroindolizidine alkaloid analogues preliminarily revealed that the basic skeleton and substitution pattern at the C13a position of the molecule, which are closely related to the spatial arrangement of the molecule, have great effects on the biological activity. To further study the in-depth influence of spatial configuration and three-dimensional (3D) conformation of the molecules on their anti-TMV activities and related structure–activity relationship (SAR), a series of D-ring opened derivatives <b>3</b>, <b>4</b>, <b>5a</b>–<b>5j</b>, <b>6</b>, and <b>7</b>, chiral 13a- and/or 14-substituted phenanthroindolizidine analogues <b>10</b>–<b>12</b> and <b>18</b>–<b>20</b>, and their enantiomers <b>ent-10</b>–<b>ent-12</b> and <b>ent-18</b>–<b>ent-20</b> were synthesized and evaluated for their anti-TMV activities. Bioassay results showed that most of the chiral phenanthroindolizidines displayed good to excellent <i>in vivo</i> anti-TMV activity. Among these compounds, <b>ent-11</b> showed more potent activity than Ningnanmycin (one of the most successful commercial antiviral agents), thus emerging as a potential inhibitor of the plant virus. Further SARs were also discussed for the first time under the chiral scenario, demonstrating that both spatial configuration and 3D conformation of the molecules are crucial for keeping high anti-TMV activity

Plot image of CD3-ECD in flow cytometry in severe cavitary PTB.

<p>Plot image of CD3-ECD in flow cytometry in severe cavitary PTB.</p

Shown in histogram, IFN-γ secretion by ELISA in supernatant of PBMC stimulated with medium (unstimulated, A), PHA(B), PPD(C) or ESAT-6(D) in five grades of subjects, p value refers to comparison of IFN-γ levels.

<p>Shown in histogram, IFN-γ secretion by ELISA in supernatant of PBMC stimulated with medium (unstimulated, A), PHA(B), PPD(C) or ESAT-6(D) in five grades of subjects, p value refers to comparison of IFN-γ levels.</p

Percentage of IFN-γ secreting CD4+ T cells among cavitary and non-cavitary PTB as well as healthy controls, using cell staining and flow cytometry.

<p>PBMC cultured with unstimulated (A), PHA(B), PPD(C) and ESAT-6(D).</p

Percentage of CD3+CD4+ cells from PBMC after culture with unstimulated (A), PHA(B), PPD(C) or ESAT-6(D) in severe cavity PTB group and mild lesion non-cavity PTB group.

<p>Percentage of CD3+CD4+ cells from PBMC after culture with unstimulated (A), PHA(B), PPD(C) or ESAT-6(D) in severe cavity PTB group and mild lesion non-cavity PTB group.</p