Synthesis of Chiral Scaffolds Based on Polyfunctional Cyclobutane β-Amino Acids

Altres ajuts: Acord transformatiu CRUE-CSICChiral scaffolds have been synthesized through selective transformations from conveniently protected cyclobutane β-amino acids. The obtained derivatives present additional functional groups, such as hydroxyl, carboxyl, or carbon-carbon triple bond, linked to the amino acid core through a flexible C or C alkyl fragment. The resultant molecules are highly versatile to be used as chiral precursors for the production of polyfunctional chemical platforms. These can be suitable for the synthesis of complex molecules, through condensation reactions, such as peptide coupling, dehydration between a carboxylic acid and an alcohol, or click chemistry. To illustrate some of these possibilities, two hybrid tripeptides have been prepared as examples of their synthetic potential

Preparació de blocs quirals per a nous agents de penetració cel·lular

Les membranes plasmàtiques protegeixen la cèl·lula d'invasions exògenes, fet que dificulta l'arribada de certs fàrmacs a les seves dianes terapèutiques intracel·lulars. En els últims anys, s'han desenvolupat diferents pèptids sintètics per internalitzar diferents molècules bioactives. Aquest article tracta de la síntesi en fase sòlida de dos pèptids tetradecamèrics híbrids mitjançant l'estratègia Fmoc/Boc. Aquests pèptids estan constituïts per un g-aminoàcid ciclobutànic i un residu de trans-g-amino-l-prolina funcionalitzat, enllaçats alternadament. Alguns d'aquests pèptids han donat bons resultats d'internalització en cèl·lules HeLa i en el paràsit leishmània, i es preveu realitzar un estudi en profunditat de les seves propietats de penetraci

Cyclobutane-based peptides/terpyridine conjugates : Their use in metal catalysis and as functional organogelators

Two new conjugates, hcptpyDP and hcptpyTP, of a terpyridine derivative incorporating artificial peptide moieties, have been synthesized and their use in the preparation of metal catalysts and organogelators has been investigated. Ru(II) complexes derived from these ligands showed electrochemical behavior and activity as catalysts in the epoxidation of olefins similar to that of Beller's catalyst. As organogelators, these conjugates were able to gelate a variety of solvents, from toluene to methanol, with satisfactory mgc (minimum gelation concentration) values. The presence of 4'-(4-carboxy)phenylterpyridine (hcptpy) moiety allows tuning the gelling properties and also influences the supramolecular self-assembling mode to produce chiral aggregates with respect to parent peptides DP and TP. In the case of the conjugates, π−π interactions provided by the aromatic moieties cooperate with inter-molecular hydrogen bonding between NH and CO in the amide groups. Further properties of peptide/terpyridine conjugates are under investigation in view of future applications

Cyclobutane-Containing Scaffolds as Useful Intermediates in the Stereoselective Synthesis of Suitable Candidates for Biomedical Purposes : Surfactants, Gelators and Metal Cation Ligands

Efficient and versatile synthetic methodologies are reported for the preparation of products that are suitable candidates to be used as surfactants, gelators for hydroxylic solvents or metal cation ligands, with potential use in several fields including biomedical applications. The common structural feature of all the synthesized products is the presence of a cis or trans-1,2- or cis-1,3-difunctionalized cyclobutane ring. In the two first cases, the key intermediates including enantiomerically pure 1,3-diamines and 1,3-amino alcohols have been prepared from β-amino acid derivatives obtained, in turn, from a chiral half-ester. This compound is also precursor of γ-amino esters. Furthermore, two kind of polydentate ligands have also been synthesized from a symmetric 1,5-diamine obtained from norpinic acid, which was easily prepared from commercial verbenone

Cyclobutane scaffold in bolaamphiphiles : Effect of diastereoisomerism and regiochemistry on their surface activity aggregate structure

Cationic bolaamphiphiles have been synthesized starting from meso cis- or chiral trans-1,2-difunctionalized cyclobutane derivatives. They include cis/trans pairs of diastereoisomers, of N- or C-centered bisamides. The goal of this work was to investigate the influence of stereochemistry and regiochemistry on their abilities as surfactants and self-assembly. Very large differences in surface coverage (2-fold), critical micellar concentration (cmc, up to 2 orders of magnitude), and aggregate structure (from lamellae to fibers) for the four molecules are remarkable due to regio- and stereochemistry differences. Computational calculations were carried out to rationalize the experimental findings and a new methodology has been developed to calculate the structure of these bolaamphiphiles at the surface. Although the four surfactants adopt a wicket-like conformation, for N-centered trans, the distance between polar heads is much larger than that for the other three molecules, as suggested by calculations. We have shown that the interplay between the regiochemistry and stereoisomerism, enhanced by rigidity of the cyclobutane ring, affects different physicochemical properties quite differently. That is, the cmc value is mainly governed by stereochemistry, with regiochemistry only modulating this value. On the other hand, regiochemistry definitely governs the morphology of the supramolecular aggregates (i.e., long fibers versus plates or spherical assemblies), with stereochemistry finely modulating their structural parameters. All these results must help in the rational design of new bolaamphiphiles with predictable properties and useful potential applications

Síntesis y estudio estructural de nuevos γ-péptidos ciclobutánicos

En el presente trabajo se ha llevado a cabo la síntesis y el estudio estructural de tres series diferentes de γ-péptidos conteniendo un ciclobutano como elemento constrictor del esqueleto péptidico. También se han sintetizado una serie de γ-péptidos híbridos formados a partir de monómeros ciclobutánicos y un derivado de prolina para su potencial uso como péptidos capaces de penetrar en las células (CPPs).En el present treball s'ha dut a terme la síntesi i l'estudi estructural de tres sèries diferents de γ-pèptids que contenen un ciclobutà com a element constrictor de l'esquelet peptídic. També s'han sintetitzat una sèrie de γ-pèptids híbrids formats a partir de monòmers ciclobutànics i un derivat de prolina per al seu potencial ús com a pèptids capaços de penetrar en les cèl·lules (CPPs)

Anillos carbonados pequeños: unidades estructurales valiosas en ingeniería molecular

Este artículo pretende ofrecer una visión general acerca de la utilidad de anillos carbonados pequeños en la construcción o modificación de moléculas orgánicas. Los ejemplos presentados muestran cómo la propia naturaleza utiliza derivados ciclopropánicos y ciclobutánicos en el metabolismo secundario y cómo los químicos pueden contribuir a proporcionar nuevos productos con propiedades estructurales y/o actividades biológicas inéditas, o mejoradas respecto a las ya conocidas. Se comentan resultados del grupo de investigación acerca de la síntesis y estudio de derivados fullerénicos, así como nucleósidos, aminoácidos y péptidos con libertad conformacional restringida debido a la incorporación en su estructura de dichos carbociclos

Carbocycle-Based Organogelators : Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties

The rational design and engineer of organogel-based smart materials and stimuli-responsive materials with tuned properties requires the control of the non-covalent forces driving the hierarchical self-assembly. Chirality, as well as cis/trans relative configuration, also plays a crucial role promoting the morphology and characteristics of the aggregates. Cycloalkane derivatives can provide chiral chemical platforms allowing the incorporation of functional groups and hydrophobic structural units able for a convenient molecular stacking leading to gels. Restriction of the conformational freedom imposed by the ring strain is also a contributing issue that can be modulated by the inclusion of flexible segments. In addition, donor/acceptor moieties can also be incorporated favoring the interactions with light or with charged species. This review offers a perspective on the abilities and properties of carbocycle-based organogelators starting from simple cycloalkane derivatives, which were the key to establish the basis for an effective self-assembling, to sophisticated polycyclic compounds with manifold properties and applications