RESUMEN
A protocol for a tandem copper-catalyzed intermolecular decarboxylation cross-coupling cascade between o-bromobenzoic acids and proline or piperic acid has been disclosed. The developed protocol allows access to a variety of synthetically useful fused benzoxazinones scaffolds with high efficiency and good functional group compatibility. A mechanistically sequential approach for the decarboxylation and dehydration coupling process was presented.
RESUMEN
A silver-catalyzed protocol for the intermolecular radical umpolung cross-coupling protocol of silyl enol ethers with activated methylene compounds is disclosed. The protocol exhibits excellent functional group tolerance, enabling the expedient preparation of a variety of tricarbonyl compounds. Preliminary mechanistic investigations suggest that the reaction proceeds through a process involving free radicals in which silver oxide has a dual role, acting as both a catalyst and a base.
RESUMEN
The Irano-Turanian region is one of the world's richest floristic regions and the centre of diversity for numerous xerophytic plant lineages. However, we still have limited knowledge on the timing of evolution and biogeographic history of its flora, and potential drivers of diversification remain underexplored. To fill this knowledge gap, we focus on the Eurasian genus Jurinea (ca. 200 species), one of the largest plant radiations that diversified in the region. We applied a macroevolutionary integrative approach to explicitly test diversification hypotheses and investigate the relative roles of geography vs. ecology and niche conservatism vs. niche lability in speciation processes. To do so, we gathered a sample comprising 77% of total genus richness and obtained data about (1) its phylogenetic history, recovering 502 nuclear loci sequences; (2) growth forms; (3) ecological niche, compiling data of 21 variables for more than 2500 occurrences; and (4) paleoclimatic conditions, to estimate climatic stability. Our results revealed that climate was a key factor in the evolutionary dynamics of Jurinea. The main diversification and biogeographic events that occurred during past climate changes, which led to colder and drier conditions, are the following: (1) the origin of the genus (10.7 Ma); (2) long-distance dispersals from the Iranian Plateau to adjacent regions (â¼7-4 Ma); and (3) the diversification shift during Pliocene-Pleistocene Transition (ca. 3 Ma), when net diversification rate almost doubled. Our results supported the pre-adaptation hypothesis, i.e., the evolutionary success of Jurinea was linked to the retention of the ancestral niche adapted to aridity. Interestingly, the paleoclimatic analyses revealed that in the Iranian Plateau long-term climatic stability favoured old-lineage persistence, resulting in current high species richness of semi-arid and cold adapted clades; whereas moderate climate oscillations stimulated allopatric diversification in the lineages distributed in the Circumboreal region. In contrast, growth form lability and high niche disparity among closely related species in the Central Asian clade suggest adaptive radiation to mountain habitats. In sum, the radiation of Jurinea is the result of both adaptive and non-adaptive processes influenced by climatic, orogenic and ecological factors.
Asunto(s)
Asteraceae , Evolución Biológica , Filogenia , Irán , FilogeografíaRESUMEN
Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.
RESUMEN
A copper-catalyzed sequence involving a Sonogashira coupling reaction and 5-exo-dig aminocyclization between a terminal alkyne and a 2-(2-bromophenyl)pyrimidine analog based on six-membered rings is presented. This protocol provides a controlled and modular approach to access a variety of synthetically useful pyrimidine-fused skeletons with high efficiency, broad substrate scope, and excellent functional group compatibility. Under acidic conditions, the (Z)-configuration of products spontaneously converts into (E)-9-benzylidene-1,9-dihydro-11H-pyrazolo[4',3':4,5]pyrimido[2,1-a]isoindol-11-ones.
RESUMEN
A method involving silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes to yield 3-substituted isocoumarins is described. The developed protocol allows convenient access to a range of synthetically useful 3-substituted isocoumarins and related fused heterocyclolactones in good to high yields, using silver tetrafluoroborate as the catalyst, and atmospheric oxygen as the terminal oxidant and the source of endocyclic oxygen. Mechanistic studies suggest the involvement of a free-radical pathway.
RESUMEN
A silver-assisted method for [3 + 2] annulation of nitrones with isocyanides has been developed. The developed protocol allows access to a variety of 2,3,4-trisubstituted 1,2,4-oxadiazolidin-5-one derivatives as single diastereomers in good to excellent yields using silver oxide as the catalyst and molecular oxygen as the terminal oxidant. A plausible mechanism involving a nucleophilic addition/cyclization/protodeargentation/oxidation pathway is proposed on the basis of experimental results.
RESUMEN
Classification of tribe Cardueae in natural subtribes has always been a challenge due to the lack of support of some critical branches in previous phylogenies based on traditional Sanger markers. With the aim to propose a new subtribal delimitation, we applied a Hyb-Seq approach to a set of 76 Cardueae species representing all subtribes and informal groups defined in the tribe, targeting 1061 nuclear conserved orthology loci (COS) designed for Compositae and obtaining chloroplast coding regions as by-product of off-target reads. For the extraction of the target nuclear data, we used two strategies, PHYLUCE and HybPiper, and 776 and 1055 COS loci were recovered with each of them, respectively. Additionally, 87 chloroplast genes were assembled and annotated. With three datasets, phylogenetic relationships were reconstructed using both concatenation and coalescent approaches. Phylogenetic analyses of the nuclear datasets fully resolved virtually all nodes with very high support. Nuclear and plastid tree topologies are mostly congruent with a very limited number of incongruent nodes. Based on the well-solved phylogenies obtained, we propose a new taxonomic scheme of 12 monophyletic and morphologically consistent subtribes: Carlininae, Cardopatiinae, Echinopsinae, Dipterocominae (new), Xerantheminae (new), Berardiinae (new), Staehelininae (new), Onopordinae (new), Carduinae (redelimited), Arctiinae (new), Saussureinae (new), and Centaureinae. In addition, we further updated the temporal framework for origin and diversification of these subtribes. Our results highlight the power of Hyb-Seq over Sanger sequencing of a few DNA markers in solving phylogenetic relationships of traditionally difficult groups.
Asunto(s)
Asteraceae/clasificación , Asteraceae/genética , Núcleo Celular/genética , ADN de Plantas/genética , Variación Genética , Filogenia , Plastidios/genética , Análisis de Secuencia de ADN , Calibración , Bases de Datos Genéticas , Geografía , Factores de TiempoRESUMEN
A silver-mediated reaction between 2-ethynyl-3-(1-hydroxyprop-2-yn-1-yl)phenols or 2-ethynyl-3-(1-hydroxyprop-2-yn-1-yl)anilines and methylene isocyanides has been developed. A sequential 5-endo-dig cyclization and [3 + 2] cycloaddition process is proposed. This synthetic strategy is atom- and step-efficient and applicable to a broad scope of substrates, allowing the synthesis of valuable substituted benzofuran- and indole-pyrroles in moderate to high yields.
RESUMEN
The halophyte model plant Eutrema salsugineum (Brassicaceae) disjunctly occurs in temperate to subarctic Asia and North America. This vast, yet extremely discontinuous distribution constitutes an ideal system to examine long-distance dispersal and the ensuing accumulation of deleterious mutations as expected in expanding populations of selfing plants. In this study, we resequenced individuals from 23 populations across the range of E. salsugineum. Our population genomic data indicate that E. salsugineum migrated "out of the Altai region" at least three times to colonize northern China, northeast Russia and western China. It then expanded its distribution into North America independently from northeast Russia and northern China, respectively. The species colonized northern China around 33.7 thousand years ago (kya) and underwent a considerable expansion in range size approximately 7-8 kya. The western China lineage is likely a hybrid derivative of the northern China and Altai lineages, originating approximately 25-30 kya. Deleterious alleles accumulated in a stepwise manner from (a) Altai to northern China and North America and (b) Altai to northeast Russia and North America. In summary, E. salsugineum dispersed from Asia to North America and deleterious mutations accumulated in a stepwise manner during the expansion of the species' distribution.
Asunto(s)
Brassicaceae/genética , Genética de Población , Tolerancia a la Sal/genética , Plantas Tolerantes a la Sal/genética , Alelos , Asia , Brassicaceae/crecimiento & desarrollo , China , Regulación de la Expresión Génica de las Plantas , Carga Genética , América del Norte , Filogenia , Federación de Rusia , Plantas Tolerantes a la Sal/crecimiento & desarrolloRESUMEN
A series of ( E)- N-aryl-4 H-thiochromen-4-imines has been conveniently obtained through a cascade reaction between o-bromobenzothioamides and terminal alkynes. This novel approach probably involved an initial generation of benzothietane-2-imine intermidates via an intramolecular Ullmann reaction under CuI/L-proline cocatalysis and alkaline conditions followed by imine alkynylation, ring opening, and cyclization sequences to provide the unexpected 4 H-thiochromen-4-imines rather than isothiochromans.
RESUMEN
CuI functions as a mild Lewis acid catalyst to promote the condensation and cyclization reaction of 2-amino-N-(2-hydroxyphenyl)benzamide and 2-bromobenzaldehyde to build the quinazoline moiety first. With the addition of Cs2CO3, it also can catalyse the subsequent intramolecular Ullmann type reaction to give 16H-dibenzo[2,3:6,7][1,4]oxazepino[5,4-b]quinazolin-16-ones in good yields.
RESUMEN
Dioxane was found to be involved in the reaction of 2-(arylethynyl)benzaldehydes and 3-aminopyrazine-2-carbohydrazide, and underwent a ring-opening reaction catalyzed by AgOTf. This domino type procedure provided an efficient method for the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields via the loss of a molecule of 3-aminopyrazine-2-carboxamide.
RESUMEN
A Cu(OAc)2-catalyzed domino tricyclization between naphthalene-1,8-diamine and 2-(phenylethynyl)benzaldehyde is described, enabling aerobic oxidative dehydrogenation coupling to access heptacyclic quinolizino[3,4,5,6-kla]perimidines. In this reaction, the formation of three new rings and four new bonds was achieved in a functional-group-compatible fashion, allowing a facile method toward fused aza-heterocycles containing both quinolizine and perimidine moieties.
RESUMEN
A consecutive Sonogashira coupling reaction, acetylene hydroamination cyclization of 2-(2-bromophenyl)quinazolin-4(3H)-ones and terminal alkynes, is described catalyzed by CuI/l-proline in the presence of Cs2CO3. This procedure provided a facile method for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-one derivatives in good yields.
RESUMEN
Dibenzoyl methane was found to undergo α-arylation of carbonyl and deacylation reaction with 2-(2-bromophenyl)-1H-benzo[d]imidazoles catalyzed by CuI in the presence of Cs2CO3, and provided an efficient synthesis of 6-arylbenzo[4,5]imidazo[2,1-a]isoquinolines via subsequent intra-molecular nucleophilic addition and dehydration.
RESUMEN
An interesting radical coupling reaction of aromatic aldehydes with isocyanides was disclosed for the synthesis of amides catalyzed by copper. According to the experimental results and mechanistic study, the isocyano group acted as an N1 synthon rather than exhibiting the carbene-like reactivity, exploiting a new reactivity profile of isocyanides.
RESUMEN
A two-marker combination of plastid rbcL and matK has previously been recommended as the core plant barcode, to be supplemented with additional markers such as plastid trnH-psbA and nuclear ribosomal internal transcribed spacer (ITS). To assess the effectiveness and universality of these barcode markers in seed plants, we sampled 6,286 individuals representing 1,757 species in 141 genera of 75 families (42 orders) by using four different methods of data analysis. These analyses indicate that (i) the three plastid markers showed high levels of universality (87.1-92.7%), whereas ITS performed relatively well (79%) in angiosperms but not so well in gymnosperms; (ii) in taxonomic groups for which direct sequencing of the marker is possible, ITS showed the highest discriminatory power of the four markers, and a combination of ITS and any plastid DNA marker was able to discriminate 69.9-79.1% of species, compared with only 49.7% with rbcL + matK; and (iii) where multiple individuals of a single species were tested, ascriptions based on ITS and plastid DNA barcodes were incongruent in some samples for 45.2% of the sampled genera (for genera with more than one species sampled). This finding highlights the importance of both sampling multiple individuals and using markers with different modes of inheritance. In cases where it is difficult to amplify and directly sequence ITS in its entirety, just using ITS2 is a useful backup because it is easier to amplify and sequence this subset of the marker. We therefore propose that ITS/ITS2 should be incorporated into the core barcode for seed plants.
Asunto(s)
Cycadopsida/genética , Código de Barras del ADN Taxonómico/métodos , ADN Espaciador Ribosómico/genética , Magnoliopsida/genética , Núcleo Celular/genética , Cycadopsida/clasificación , ADN de Cloroplastos/clasificación , ADN de Cloroplastos/genética , ADN Intergénico/clasificación , ADN Intergénico/genética , Bases de Datos Genéticas/estadística & datos numéricos , Endorribonucleasas/clasificación , Endorribonucleasas/genética , Magnoliopsida/clasificación , Nucleotidiltransferasas/clasificación , Nucleotidiltransferasas/genética , Filogenia , Proteínas de Plantas/clasificación , Proteínas de Plantas/genética , Reproducibilidad de los Resultados , Ribulosa-Bifosfato Carboxilasa/clasificación , Ribulosa-Bifosfato Carboxilasa/genética , Especificidad de la EspecieRESUMEN
Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.
RESUMEN
Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.