Angiogenesis, the sprouting of new blood vessels from pre-existing vessels, is a remarkable feature of tumours growth and metastasis. The in vivo inhibition of this receptor by cyclic peptides containing RGD sequence may be used to selectively suppress these disease¹. Our research group has developed a new methodology² for the evaluation of new antiangiogenic compounds, based in the genetic expression analysis using CGH array system. The RGD mimetics activity can be modified by the presence of ester-bond³, Therefore, we decided to prepare some depsipeptides analogous to the RGD-β-lactam compounds and evaluate their activity performing a genetic expression analysis. We also have evaluated the activity of open-chain compounds without RGD formal structure. The cyclic depsipeptides have demonstrated a very effective inhibitory activity. In the other hand the open-chain compounds have a surprising behavior, demonstrating a similar gene activation. This way, we call into question the essential need of RGD sequence to have an interaction between ligand and the receptor of the integrin^{4, 5}.

1. da Ressurreicao, A. S. M.; Vidu, A.; Civera M.; Belvisi L.; Potenza, D.; Manzoni, L.; Ongeri, S.; Gennari, C.; Piarulli, U.; Eur. 2009, 15, 12184.
2. Aizpurua, J. M.; Ganboa, J. I.; Palomo, C.; Loinaz, I.; Oyarbide, J.; Fernandez, X.; Belentová, E.; Fratila, R. M.; Jiménez A.; Miranda, J. I.; Laso, A.; Ávila, S.; Castrillo, J. L.; ChemBioChem, 2001, 11, 401.
3. Cupido, T.; Spengler, J.; Ruiz-Rodriguez, J.; Adan, J.; Mitjans, F.; Puilats, J.; Albericio, F.; Chem. Int. Ed., 2010, 49, 2732.
4. Xiong, J. P.; Stehle, T.; Zhang, R.; Joachimiak, A.; Frech, M.; Goodman, S. L.; Arnaout, M. A.; Science, 2002, 296, 151.
5. Craig, D.; Gao, M.; Schulten, K.; Vogel, V.; Structure, 2004, 12, 2049.

Asymmetric Mizoroki-Heck reaction is one of most important palladium(0)-catalyzed C-C bond-forming reactions, which has allowed the preparation of optically active molecules with tertiary and quaternary stereocenters. In particular, Heck-Heck cascade reactions are a powerful synthetic strategy for rapidly increasing structural and stereochemical complexity, allowing the construction of polycyclic frameworks in a one-pot operation. For this purpose, the σ-alkylpalladium intermediate, resulting from the migratory insertion of the arylpalladium to the alkene, may undergo an insertion with an alkene in inter- or intramolecular way, so carbopalladation is repeated one or several times prior to b-hydride elimination. In connection with our work in palladium-catalyzed reactions,[1] we have developed the enantioselective palladium-catalyzed Heck-Heck cascade reaction of N-benzyl 2,3-dialkenylpyrroles, using chiral ligands for palladium. A 6-exo Mizoroki–Heck reaction generates the quaternary stereocenter, giving rise to the s-alkylpalladium intermediate that undergoes a 6-endo insertion to give the Lycorane framework. Details of these transformations will be given.

The seasonality of upper respiratory tract infections and their relationship to asthma

Alejo¹ and D. Quesada²

¹ Miami Dade College, Wolfson Campus, Miami FL

² School of Science, Technology, and Engineering Management, St. Thomas University, Miami Gardens, FL

The impact of weather conditions on both human health and the spread of diseases is a question addressed by Biometeorology and the answer is very important for health management and disease control. Upper respiratory tract infections due to different viruses (respiratory syncytial virus (RSV), rhinovirus influenza, human metapneumovirus) and bacteria (corynebacterium diphtheriae, chlamidia pneumonia) show seasonal patterns, mostly associated with the changes in the immune response in different seasons. Such infections often trigger asthma episodes that might be difficult to treat, especially in elderly and young children. This project is aimed at describing and modeling the pattern of seasonality in South and Central Florida due to both asthma and upper respiratory tract infections, when each one is considered the primary diagnosis at the Emergency Room (ER). The Department of Health of Florida via the Florida Asthma Coalition provided the health data used in this study. As a result of the statistical analysis, the peak of seasonality for Central and South Florida is centered in late January and early February. Compared with the rest of continental USA, this shift in time is associated with cold conditions arriving to South Florida in these periods. Cold and dry air is affecting the lining of epithelial cells from the respiratory tract in addition to the thermal stress due to the convective loss during respiration. Together, these conditions affect the response of the immune system and facilitate the reproduction of infective agents. A mathematical model based on the SEIR epidemic model is adapted to account for both, recovery from infections and a further development of asthma symptoms. The results might be very beneficial to medical practitioners as well as the pave the way to study potential effects due to global climate changes and the spread of different vector-borne diseases in addition to the spread of allergies.

Pyranone rings have shown a great applicability in diverse organic reactions due to their multiple functionalities and also because the compounds that are obtained from such reactions are present in the framework of several natural products. In this work, we chose 2H-pyran-3(6H)-one as substrate to continue the program directed toward the development of cascade organocatalytic enantioselective reactions.  On the one hand, we have described a new oxa-Michael/Michael cascade reaction between a,b-unsaturated aldehydes and racemic 6-hydroxy-2H-pyran-3(6H)-one in presence of a secondary amine, providing a direct access to the hexahydro-4H-furo[2,3-b]pyrane framework in a straightforward way. The reaction takes place under the known combination of iminium/enamine manifolds and leads to the formation of the final products with high yields and stereocontrol. Moreover, it is worth to mention that this is the first example where a hemiacetal is employed as an O-pronucleophile in an oxa-Michael/Michael reaction under iminium activation.¹ On the other hand, 6-acetoxy-2H-pyran-3(6H)-one was employed in an efficient procedure to synthesize tetrahydro-1H-isochromanes, by exploiting the potential of dienamine catalysis to activate the g-position of a,b-unsaturated aldehydes. The target compounds were obtained in excellent yields and excellent enantio- and diastereocontrol in a [4+2]/elimination cascade process.² It should be highlighted that in both processes a racemic starting material is transformed into an enantiopure product in a Dynamic Kinetic Asymmetric Transformation (DYKAT) that proceeds with the consecutive generation of four and three stereocenters in the above mentioned reactions.

Herein we present a practical and selective route to synthetically usefull propargylic amines and alcohols.[1] The key of both approaches is the combined use of an α,α-dialkylprolinol ether catalyst and a Brønsted acid that leads to adducts with high levels of diastereo- and enantiocontrol (anti/syn up to 90:10, ee up to 95%).  In the aldol addition it was  also observed that the presence of CuI as a third catalyst component, generally provided an increase in reaction diastereoselectivity (anti/syn up to 95:5). This study uncovers a new case of chiral enamine catalysis in which α,α-dialkylprolinol silyl ethers perform better than their parent α,α-diaryl analogs. The resulting densely funcionalyzed adduts may be transformed into  more complex systems taking advantage of the chemistry of the triple bond.

Our group have developed an offspring of densely substituted unnatural L- and D- pyrrolidine derivatives 3 and 4 with endo- or exo- diastereoselectivity, respectively, in high enantioselectivities.[1] Encouraged by the efficiency of Proline-based organocatalysts in several C-C bond transformations, these novel densely substituted pyrrolidines (3 and 4) have been used as organocatalysts in the Michael reaction yielding the corresponding addition adduct 6.[2] These products may possess the same or opposite stereochemistry obtained under natural L-Proline organocatalysis depending on the stereochemistry of the catalyst used (endo_L-3,4aa or L-Proline vs. exo_L-3,4aa). Computational studies have been performed in order to gain insight into the mechanism and also, the influence of the substituents´ nature and additional side groups in the catalysts have been studied. As a coda, reactivity of the catalysts against a novel double electrophile is shown.

[1] Conde, E.; Bello, D.; de Cózar, A.; Sánchez, M.; Vázquez, M. A.; Cossío, F. P. Chem. Sci. 2012, 3, 1486-1491

[2] a) Xu, L. W.; Luo, J.; Lu, Y. Chem. Comm. 2009, 1807-1821. b) Vicario, J. L.; Badía, D.; Carrillo, L.; Reyes, E. Organocatalytic Enantioselective Conjugate Additions Reactions, RSC Publishing: Cambridge UK 2010

An efficient organocatalytic route to tertiary thiols is reported based on conjugate additions to nitro olefins of 5H-thiazol-4-ones as new sulfur based carbon pronucleophiles. Key for that realization is the development of ureidopeptide-based Brønsted bases, a new subclass of Brønsted base catalysts. Success in this transformation is presumably due to the reaction model outlined above. This model nicely accounts for the best behavior of quinolyl thiazolone substrates for this reaction, in comparison to that of naphthyl based thiazolones which provided adducts with significantly lower levels of stereoselectivity, both diastereo- and enantioselectivity.

Welcome to the MODEC2017 workshop. This is Amazon State University's (UEA) first workshop, devoted to the promotion and application of  the Multidisciplinary Sciences to the development of natural products and agro-industrial processes in Ecuadorian Amazon regions. This includes the application of Information and Communications Technologies (ICTs) for data analysis and computational model including the fields of Agro-industrial Engineering, Chemistry, Chemical Engineering, Biotechnology, Veterinary Medicine, and/or Environmental Sciences, etc.  This workshop runs both online and on location at the university. The online portion of the workshop is powered by the SciForum platform of MDPI, hosted by the MOL2NET International Conference on Interdisciplinary Sciences. Additionally, the physical component of the workshop is also scheduled to run through the Department of Earth Sciences (Facultad de Ciencias de la Tierra) at Universidad Estatal Amazónica (UEA), Puyo, Ecuador. Please, contact the workshop chairmen for further details. Paper submission is already open and  the publication of papers for conference purposes in SciForum platform is free of cost.

Effect of Brain network topologies on the synchronization of neuronal oscillations – Is this the gateway to the understanding of Central Nervous disorders?

N. Astudillo, M. Garcia – Russo, and D. Quesada

School of Science, Technology, and Engineering Management, St. Thomas University, Miami Gardens, FL 33054

The Brain Project is aimed at the understanding of the inner working of the brain and how the complex network formed by neurons yields to emergent behaviors at different scales. These varieties of behaviors resulting from the collective action of groups of neurons and cortical areas are hypothesized to be crucial for the comprehension of Central Nervous Disorders (CND) as for example, epilepsy, schizophrenia, Parkinson, Alzheimer, concussion in athletes, and many others. Such conditions seem to appear due to some kind of bottleneck effect while nervous signals spread through the brain wide web. In this communication, we are evaluating the impact of brain network topologies on the synchronization of different neuronal networks. Two approaches are adopted, a microscopic one, addressing the interaction between groups of neurons and following the dynamics of the FitzHugh-Nagumo model, and the mesoscopic one, addressing the interaction between patches in the cortex and following the Kuramoto model, capable to integrate the action of groups of neurons as a whole unit. The relationship between the topological indices characterizing the networks and the attained synchronization is studied. Results are compared with images obtained from functional MRI (fMRI) and EEK. A potential translation of this research into epilepsy treatment and surgery is addressed also.

    Nanotechnology has led to the development of new materials with unique properties and a wide variety of applications. Meanwhile, it has raised great concerns regarding their properties and potential adverse effects to humans and the environment. In this work, a Quantitative Structure-Activity Relationship (QSAR) modeling study was carried out for predicting the adsorption property of a set of 59 environmental pollutant aromatic compounds into multi-walled carbon nanotubes. We report a systematic evaluation of multiple linear regression (MLR) and artificial neural network (ANN) methods along with a variety of structure representations and feature selection algorithms. Judging from the attained statistical results, our derived QSAR models have an acceptable overall accuracy and robustness, as well as good predictivity on external data. This QSAR study suggested also that the adsorption ability of these compounds is mainly explained by size, charge and hydrophobicity factors. Moreover, it showed to be a simple, precise and credible tool forward-predicting the adsorption of aromatic compounds by multi-walled carbon nanotubes.