Total Synthesis of (−)-Xylogranatopyridine B via a Palladium-Catalyzed Oxidative Stannylation of Enones

We report a total synthesis of the pyridine-containing limonoid alkaloid (−)-xylogranatopyridine B in 11 steps from commercially available dihydrocarvone. The central pyridine ring was assembled by a late-stage fragment coupling approach employing a modified Liebeskind pyridine synthesis. One fragment was prepared by an allyl-palladium catalyzed oxidative enone β-stannylation, in which the key bimetallic β-stannyl palladium enolate intermediate undergoes a β-hydride elimination. This methodology also allowed introduction of alkyl and silyl groups to the β-position of enones

Distribution of sequence reads from human plasma (A), other sample types (B) and public domain data (C) among different sequence categories.

<p>The sample identifies were listed on the top, the sequence mapping criteria were indicated on the bottom and the list of different sequence categories is indicated on the right of each figure. See text for detailed description of Strategy 0, Strategy 1 and Strategy 2 sequence mapping criteria.</p

Examples of identical exogenous sequences observed in fetal bovine serum used in culture and RISC complex from cultured cells.

<p>Examples of identical exogenous sequences observed in fetal bovine serum used in culture and RISC complex from cultured cells.</p

Number of sequence reads mapped to common food items such as cereal grains (A) and others (B).

<p>The Y-axes are the number of reads in log 10 value and individual species are indicated on the X-axis. The number of reads used in the figures represented the averages from all 9 plasma samples used in the study. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051009#pone-0051009-g004" target="_blank">Figure 4C</a> shows the difference in the abundance of reads mapped to common cereal gains between serum sample from a Chinese individual (open bars) and the plasma samples (Caucasian) used in the study (solid bars).</p

Examples of exogenous RNAs observed in fetal bovine serum and associated with RISC complex isolated from 293T cells that may generate miRNA precursor like hairpin structure.

<p>The regions indicated by black brackets lines were observed in sequencing results and listed on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051009#pone-0051009-t004" target="_blank">Table 4</a>. RNAfold web server (<a href="http://www.rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi" target="_blank">www.rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi</a>) was used to generate the putative secondary structure.</p

Results of additive binomial model examining the association between trial arm and primary outcome (VL<400 copies/mL) in per protocol population adjusted for demographic and clinical characteristics (n = 218).

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Expression of Enpp1 in breast cancer cell lines.

<p>Enpp1 (<b>A, B</b>) mRNA and (<b>C</b>) protein expression was determined in (A) NT2.5 murine breast cancer cells and bone sublines, and (B, C) immortalized normal human mammary epithelial cell lines and human breast cancer cell lines by (A, B) qRT-PCR and (C) Western analysis. (A, B) Data are representative of three independent experiments performed in triplicate and expressed as the mean ± s.e.m (**p<0.01, ***p<0.001). (C) Protein expression was determined by Western analysis performed on equal amounts of protein from total cell lysates.</p

Effect of Enpp1 on the development of bone metastasis.

<p>MDA-MB-231 cells stably expressing Enpp1 or empty vector (EV) were injected into the (<b>A, B</b>) tibia (n = 9/group) and (<b>C, D</b>) left cardiac ventricle (n = 5/group) of athymic nude mice and digital radiographic imaging was performed at weekly intervals. (A, C) Osteolytic area and (B, D) tumor area were measured on radiographic images and histological sections, respectively (*<i>p</i><0.05, **<i>p<</i>0.01). Representative images are shown at 4 weeks following tumor cell administration. Black outlined areas on histological images indicate areas of tumor.</p

Results of additive binomial model examining the association between trial arm and primary outcome (VL<400 copies/mL) including an interaction term between the intervention and age.

Results of additive binomial model examining the association between trial arm and primary outcome (VL<400 copies/mL) including an interaction term between the intervention and age.</p

Affected pathways by transfecting the synthetic exogenous RNA sequences.

<p>Affected pathways by transfecting the synthetic exogenous RNA sequences.</p