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Treatment of cis-fused bicyclic diene dicarboxylates with Li/naphthalene triggers a tandem ring-opening and transannular cyclization process that stereoselectively yields hydroazulenes and hydrindanes derivatives. Cyclononadienyl diesters, which can be isolated after the ring-opening step by judicious choice of the reaction conditions, undergo a tandem conjugate addition/intramolecular Michael addition upon treatment with chiral lithium amides to give bicyclic β-amino esters in a process where 4 contiguous stereocenters are formed with high diastereocontrol. A concise route toward the highly enantioenriched AEF ring core of the aconitine-type alkaloids has been developed as an application of this methodology. The starting cis-fused bicyclic dicarboxylates are easily prepared in one step by reductive alkylation of diisopropyl phthalate (Na/THF, followed by the appropriate bis-electrophiles).

A práctica de calquera ciencia natural ten moitísimo de pescuda intelectual que persegue comprender en profundidade os fenómenos observados e a súas causas e, como corolario dese entendemento, xerar a posibilidade de controlalos para facelos (máis) útiles. Cal sería, entón, un bo consello que un investigador veterano podería darlle a un mozo que emprende a súa primeira peregrinación polos camiños da investigación en Química? Sen dúbida, que encha a súa mochila intelectual coa Lóxica de Aristóteles, as ensinanzas de Os Tres Príncipes de Serendip, a Mecánica Cuántica e a Táboa Periódica. E se carga tamén unha navalla de Ockham en vez dunha suíza, moito mellor.

1,2-Aromatic diesters can be transformed into strained bridged polycyclic structures by a two-step procedure consisting of an initial reductive alkylation promoted by alkaline metals, followed by a...

Lithiation reactions of tertiary benzylic esters and carbamates have been studied. Kinetic methodology revealed that a two-step reaction pathway should be considered for these reactions, where either the lithium precomplexation and/or the proton transfer steps can be rate determining. Kinetic isotopic effects were evaluated by comparison of the lithiations of the corresponding protio/deutero substrates, and the results obtained support the notion that lithium precomplexation is taking place on the reaction pathway and that it is the rate-determining step in this transformation.

1,2-Aromatic diesters can be transformed into strained bridged polycyclic structures by a two-step procedure consisting of an initial reductive alkylation promoted by alkaline metals, followed by a reaction of the resulting unsaturated diesters with Me

This is the peer reviewed version of the following article:Navarro-Vázquez, A., Santamaría-Fernández, R., & Sardina, F. (2018). MSpin-JCoupling. A modular program for prediction of scalar couplings and fast implementation of Karplus relationships. Magnetic Resonance In Chemistry, 56(6), 505-512, which has been published in final form at https://doi.org/10.1002/mrc.4667. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions MSpin‐JCoupling is a modular program for the prediction of scalar couplings using a large variety of Karplus relationships. The program was specially designed for small molecule analysis and can be run in graphical or command‐line mode. The architecture of the program is highly modular, and new equations can be rapidly implemented, through a complete C++ programming interface, and deployed as run‐time loadable plugins Ministerio de Ciencia e Innovación. Grant Number: PET2008‐074 Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia. Grant Number: Consellería de Educación 2009/071 Spanish Ministerio de Ciencia e Innovación. Grant Number: PET2008‐074 Xunta de Galicia for a Parga Pondal. Grant Number: Consellería de Educación 2009/071 SI

This is the peer reviewed version of the following article: Domínguez, J., Fernández-Nieto, F., Brea, J., Catto, M., Paleo, M., & Porto, S. et al. (2016). 8-Aminomethyl-7-hydroxy-4-methylcoumarins as Multitarget Leads for Alzheimer's Disease. Chemistryselect, 1(11), 2742-2749, which has been published in final form at https://doi.org/10.1002/slct.201600735. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions This work is part of our ongoing research in the discovery of multitarget therapeutic agents for Alzheimer's disease (AD). A literature screening, based on our recently proposed pharmacophore, led to the identification of 8‐aminomethyl‐7‐hydroxy‐4‐methyl coumarins as potential multitarget leads for AD. The results of a computer‐assisted protocol developed by us to validate multitarget hits for AD indicated that our coumarin candidates were viable leads only for AChE inhibition as later validated by biological assays. The results of BChE binding and propidium displacement assays indicate that our first generation compounds bind to the PAS site in AChE. We designed new generations of coumarin derivatives with a longer substituent at position 8 aimed at leads with more efficient interaction at the catalytic anionic site (CAS). Inhibition data and docking simulations indicated that an anilino‐capping group reached the CAS region of AChE and determined also a higher inhibitory potency towards BChE. The best compound obtained, with a N‐benzylpiperidine fragment, displayed sub‐micromolar affinity for AChE, affinity for BChE, and precluded Aβ‐amyloid aggregation with a potency similar to that of 9,10‐anthraquinone, making it a multitarget lead viable for further improvement Financial support from the Ministerio de Economia y Competitividad of Spain (Project CTQ2014‐55208‐P) and the Xunta de Galicia (10CSA209063PR and GRC2014/029) is gratefully acknowledged. The Italian authors thank the University of Bari for partial financial support (Fondi di Ateneo 2014–2015) SI

A two-step, stereoselective procedure for the synthesis of nine- and ten-membered carbocycles from readily available phthalates is described. A variety of dialkyl phthalates have been transformed into [6,n]-fused bicyclo systems (n = 5, 6, 7) by a dearomatization/cyclization process and then converted into cyclonona- and cyclodecadienes through a bond cleavage reaction, whereby both processes are promoted by alkaline metals in THF.