Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: El acceso a la versión del editor puede requerir la suscripción del recurso Access to the published version may require subscription Mo(CO) 6 from 1.0 equiv (43% conversion, entry 1 in Table 149 1) to 0.5 equiv (67% conversion, entry 2 in 199 This good trans-diastereoselectivity is remarkable, revealing a 200 marked preference for C−H activation of the pro-S methyl 201 group of (+)-3.23e Importantly, the major (−)-trans-9 202 diastereomer could be isolated in 75% yield with no appreciable 203 loss of enantiopurity (97% ee) upon standard chromatography. 204Although the structure of the bimetallic complex of γ-205 cyclopalladation of tert-leucine derivative (+)-1 (complex A) 206 strongly suggested that the NH−SO 2 Py directing group is 207 crucial for this transformation, we were interested in confirming 208 this issue by screening other potentially coordinating N-209 protecting groups. For this purpose, a set of L-valine derivatives 210 (substrates 4−8) were examined in the carbonylation reaction 211 under the optimized conditions, and the results are summarized 212 in Table 2. While L-valine methyl ester hydrochloride 213 decomposed under the reaction conditions (entry 2 in Table 214 2), the NH-Ts derivative 5 and the NH-(2-thienyl)sulfonyl 215 derivative 6 were recovered unaltered without detecting any 216 carbonylation product (entries 3 and 4, respectively, in Table 217 2). The reaction of the (8-quinolyl)sulfonyl and (2-pyridyl)-218 carbonyl derivatives (7 and 8, respectively) led to a complex 219 mixture of products in low conversion (<10%) (entries 5 and 6 220 in Table 2). Interestingly, the lack of reaction efficiency 87 (75) e 5.7:1 (9) 9 7 2 −(4)a Reaction conditions are identical to those given in Table 1 This method was extended to β-amino acid derivatives, as 260 exemplified by the clean cyclocarbonylation of β-amino ester 261 (±)-19, affording the product (±)-20 as a separable 3.8:1 262 mixture of trans/cis diastereoisomers in good overall yield 263 (76%). 264Extension of the Method to Simple Aliphatic Amines. 265 The broad substrate scope displayed by this reaction with α-266 amino acid derivatives prompted us to explore the extension of 267 this method to simple aliphatic amine derivatives. We first 268 tested if compound (−)-21, analogue to tert-leucine derivative 269 1 but lacking the methyl ester moiety, could undergo γ-270 cyclometalation. The stoichiometric reaction of (−)-21 with 271 Pd(OAc) 2 (1.0 equiv) in acetonitrile at 60°C for 3.5 h, cleanly 272 provided, after simple recrystallization, the expected bimetallic 273 complex B in 91% yield (unambiguously determined by singles3 274 crystal X-ray diffraction (XRD) analysis; see Scheme 3), which 275 presents an analogous structure to complex A. This result demonstrated that the ester group at the α-277 position of the previously studied α-amino ester derivatives was 278 not essential for the C−H activation step. Fu...

Switchable site-selectivity through catalyst control is achieved in the direct functionalization of picolinamides that contain two distinct C–H sites to construct diverse scaffolds from the same starting material.

Understanding the relationship between the location of nanoparticles (NPs) in an organic matrix and their catalytic performances is essential for catalyst design. Here we show that catalytic activities of Au, Ag and CuNPs stabilized by dendrimers using coordination to intradendritic triazoles, galvanic replacement or stabilization outside dendrimers strongly depends on their location. AgNPs are found at the inner click dendrimer periphery, whereas CuNPs and AuNPs are encapsulated in click dendrimer nanosnakes. AuNPs and AgNPs formed by galvanic replacement are larger than precursors and only partly encapsulated. AuNPs are all the better 4-nitrophenol reduction catalysts as they are less sterically inhibited by the dendrimer interior, whereas on the contrary CuNPs are all the better alkyne azide cycloaddition catalysts as they are better protected from aerobic oxidation inside dendrimers. This work highlights the role of the location in macromolecules on the catalytic efficiency of metal nanoparticles and rationalizes optimization in catalyst engineering.

A practical Cu-catalyzed picolinamide-directed o-amination of anilines showing excellent mono-substitution selectivity and high functional group tolerance has been developed.

BackgroundFoxE1 is a thyroid-specific forkhead transcription factor essential for thyroid gland development, as well as for the maintenance of the thyroid differentiated state in adults. FoxE1 recognizes and binds to a short DNA sequence present in thyroglobulin (Tg) and thyroperoxidase (Tpo) promoters, but FoxE1 binding to regulatory regions other than Tg and Tpo promoters remains almost unexplored. Improving knowledge of the regulatory functions of FoxE1 is necessary to clarify its role in endocrine syndromes and cancer susceptibility.Methodology/Principal FindingIn order to further investigate downstream FoxE1 targets, we performed a genome-wide expression screening after knocking-down FoxE1 and obtained new insights into FoxE1 transcriptional networks in thyroid follicular cells. After validation, we confirmed Adamts9, Cdh1, Duox2 and S100a4 as upregulated genes and Casp4, Creld2, Dusp5, Etv5, Hsp5a, Nr4a2 and Tm4sf1 as downregulated genes when FoxE1 was silenced. In promoter regions of putative FoxE1-regulated genes and also in the promoters of the classical thyroid genes Nis, Pax8 and Titf1, we performed an in silico search of the FoxE1 binding motif that was in close proximity to the NF1/CTF binding sequence, as previously described for other forkhead factors. Using chromatin immunoprecipitation we detected specific in vivo FoxE1 binding to novel regulatory regions in two relevant thyroid genes, Nis and Duox2. Moreover, we demonstrated simultaneous binding of FoxE1 and NF1/CTF to the Nis upstream enhancer region, as well as a clear functional activation of the Nis promoter by both transcription factors.Conclusions/SignificanceIn search for potential downstream mediators of FoxE1 function in thyroid cells, we identified two novel direct FoxE1 target genes. To our knowledge, this is the first evidence regarding the implication of Nis and Duox2 in executing the transcriptional program triggered by FoxE1. Furthermore, this study points out the important role of FoxE1 in the regulation of a large number of genes in thyroid cells.

A practical picolinamide-directed C-H functionalization/alkyne annulation of benzylamine derivatives enabling access to the previously elusive 1,4-dihydroisoquinoline skeleton was developed using molecular O as the sole oxidant and Co(OAc) as precatalyst. The method is compatible with both internal and terminal alkynes and shows high versatility and functional-group tolerance. Furthermore, full preservation of enantiopurity is observed when using non-racemic α-substituted benzylamine derivatives. Kinetic analysis of the reagents and catalyst, labeling experiments, and the isolation and identification of catalytically competent Co-complexes revealed important insights about the mechanism.

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on their external surface is reported. This system is able to transport single oligonucleotide strands into cells, avoiding the electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating in physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the nanoparticles outer surface. As nucleic acid model, a single stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalized with the third generation of neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro using a human osteoblast-like cell line, achieving good levels of internalization of the vector DNA/carbosilane dendron functionalized material without affecting cellular viability.

A practical Cu-catalyzed direct ortho-halogenation of anilines under aerobic conditions has been developed. The reaction shows typically excellent mono-substitution selectivity, high ortho-regiocontrol and large functional group tolerance.