Crystal structure of the N-benzyloxycarbonyl-Alanyl-Phenylalanyl-methyl ester: the importance of the H-bonding pattern

Large crystals of the methyl ester of the N-a-benzyloxycarbonyl protected Ala-Phe dipeptide (Z-AF-OMe) were obtained after the very slow evaporation of a solution of the corresponding carboxylic acid (Z-AF-OH) in methanol containing an excess of HCl. The structure was confirmed by single crystal X-ray diffraction data. It crystallizes in the orthorhombic space group P212121 with unit cell dimensions a = 5.0655(6) Å, b = 8.4614(8) Å, c = 46.856(5) Å, V = 2008.3(4) Å3, Z = 4. In the crystal, the molecules form hydrogen bonded chains running along the a axis of the unit cell. Other secondary interactions are also discussed

Cooperative Education in Green Chemistry: The Spanish Experience

A common postgraduate training in Green Chemistry is currently being carried out by several Spanish universities. This initiative considers the corresponding Máster and PhD programs in Sustainable Chemistry and has been successfully achieved with the participation of experts from different Universities and Research Institutions grouped within the coverage of the Spanish Network on Sustainable Chemistry (REDQS). A cooperative effort and a modular design are the key elements that have allowed maintaining the Spanish Interuniversity Máster and PhD programs for more than a decade, providing a high level of quality and a unique possibility, for many students, of being trained at an advanced level in Green Chemistry

Macrocycle Synthesis by Chloride-Templated Amide Bond Formation

A new family of pseudopeptidic macrocyclic compounds has been prepared involving an anion-templated amide bond formation reaction at the macrocyclization step. Chloride anion was found to be the most efficient template in the macrocyclization process, producing improved macrocyclization yields with regard to the nontemplated reaction. The data suggest a kinetic effect of the chloride template, providing an appropriate folded conformation of the openchain precursor and reducing the energy barrier for the formation of the macrocyclic product.This work was supported by the Spanish Ministry of Science and Innovation (CTQ2012-38543-C03) and Generalitat Valenciana (PROMETEO/2012/020). V.M.-C. thanks Generalitat Valenciana for a postdoctoral fellowship (APOSTD/ 2013/041)

Kinetic Analysis for Macrocyclizations Involving Anionic Template at the Transition State

Several kinetic models for the macrocyclization of a C2 pseudopeptide with a dihalide through a SN2 reaction have been developed. These models not only focus on the kinetic analysis of the main macrocyclization reaction, but also consider the competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes

Chiral catalysts immobilized on achiral polymers: effect of the polymer support on the performance of the catalyst

Positive effects of the polymeric support on the performance of supported chiral catalysts, in terms of activity, stability and selectivity–enantioselectivity, have been reported when the support is properly selected and optimized opening the way to the design of more efficient catalytic systems

Synthesis of new fluorescent pyrylium dyes and study of their interaction with N-protected amino acids

Six new 6-styryl-2,4-diarylpyrylium salts have been synthesized and fully characterized by means of 1H/13C NMR, HRMS, UV-vis and Steady-State/Time-Resolved Fluorescence spectroscopies. This set of molecules is composed of a core pyrylium fluorophore, an amino acid (valine or phenylalanine), and an alkylic chain of variable length. The emissive properties (fluorescence quantum yields and lifetimes and radiative deactivation rate constants) in dichloromethane, acetonitrile and PBS have been recorded. The interaction of these pyrylium salts with aminoacids in their N-protected forms has been studied by means of fluorescence quenching, using the Stern–Volmer methodology. It has been found that dynamic (collisional) quenching is the most prevalent process for all the fluorescent molecules, irrespective of the amino acid building block or the length of the alkyl chain. The emission of the pyrylium molecules is strongly quenched by Z-Trp-OH and to a lesser extent by Z-Tyr-OH and Z-Met-OH and no quenching was measured with Z-Ala-OH, Z-Val-OH and Z-Phe-OH. A small degree of ground-state complexation was observed for receptor 8a and by Z-Trp-OH (upward curvature in the Stern–Volmer plot). Complementary 1H-NMR titrations demonstrated the existence of such a weak ground state complex

Macrocyclization Reactions: The Importance of Conformational, Configurational, and Template-Induced Preorganization

The success of a given macrocyclization reaction involves a very delicate balance of many different factors. First, a proper understanding of the basic thermodynamic and kinetic concepts underlying these processes is essential in defining the strategies to obtain the targeted cyclic structures and the experimental elements to be optimized. essential element for achieving high yields in a macrocyclization process is the appropriate selection of the disconnection site. This defines the reaction used for the key step, which will clearly affect the overall process, but also delineates the nature and structure of the immediate linear precursor. The presence of structural elements, including configurational elements, able to induce a favorable folding of this linear precursor in such a way that both reactive ends approach with the proper orientation provides significant enhancements in macrocyclizations. The use of templates of very different natures is a versatile strategy to overcome the limitations of the other macrocyclization strategies. The use of templates has allowed the preparation of a variety of macrocyclic structures in better yields and usually in shorter reaction times, and often allows easier purification protocols.Financial support of the Spanish Ministry of Science and Innovation (CTQ2012-38543-C03) and Generalitat Valenciana (PROMETEO/2012/020) is acknowledged. V.M.-C. thanks the Spanish Ministry of Science and Education for a predoctoral fellowship (FPU AP2007-02562) and Generalitat Valenciana for a VALi+d postdoctoral fellowship (APOSTD/2013/041). M.D.P. thanks the Spanish Ministry of Education for a postdoctoral fellowship and UGC India for a Startup Grant

Pseudopeptidic Compounds for Biocompatible Gels: A Review

Simple pseudopeptides derived from natural amino acids can be designed and prepared as efficient gelators for a variety of solvents, and with a high potential for biocompatibility. The appropriate selection of structural components, reviewed herein, shows how to produce gels with tailored properties, including high thermal stability

Open chain pseudopeptides as hydrogelators with reversible and dynamic responsiveness to pH, temperature and sonication as vehicles for controlled drug delivery

A new family of open chain-pseudopeptidic compounds displaying a pendant carboxylic group have been prepared with excellent yields. Their self-assembly has been studied under different conditions and in different media. Some of the compounds obtained have revealed to act as very efficient hydrogelators at low concentrations (CGC 1 mg mL−1). The resulting hydrogels show some interesting properties, including a high thermal stability, with the hydrogels maintaining their structure at temperatures above 65 °C, and their reversible dynamic sol–gel behavior being responsive to thermal and sonochemical inputs and to changes in the basic/acidic properties of the medium. Preliminary studies for controlled drug delivery have been carried out using a Franz Cell and employing a skin pig membrane, confirming that these Low Molecular Weight Gelators (LMWGs) can be appropriate vehicles for the controlled transdermal delivery of small-molecule drugs.Funding for open access charge: CRUE-Universitat Jaume

Cu2+ recognition by N,N′-benzylated bis(amino amides)

Two new C 2 -symmetric N , N ’ -benzylated bis(amino amides) have been synthesised and their interaction with di ff erent transition metals studied using a variety of techniques including UV-Vis and CD spec- troscopy or ESI-MS. The determination of the corresponding stability constants with Cu 2+ has been possi- ble, in H 2 O/CH 3 CN 7/3 v/v, for one of these ligands ( 4 ) using potentiometric titrations. The results obtained reveal that N -benzylation a ff ords signi fi cant changes to their properties and is accompanied by an appreciable decrease in the corresponding complexation stability constants. However, this, along with the low kinetics associated to Ni 2+ , facilitates the recognition of Cu 2+ by 4 that can be followed by the naked-eye up to the submillimolar range. Very interestingly, the chiral nature of this ligand provides an intense and well de fi ned CD curve for the corresponding Cu 2+ complex, very sensitive to the coordination geometry, facilitating the analysis of this interaction even at the μ M range. The formation by both ligands ( 3 and 4 ) of square planar complexes with Cu 2+ and Ni 2+ displaying a 1 : 1 stoichiometry was con fi rmed by their X-ray crystal structuresFinancial support from Spanish MINECO (CTQ2015-68429-R), Generalitat Valenciana (PROMETEO/2016/071) and PPI-UJI (P1-1B-2013-38) is gratefully acknowledged. L. G. thanks Generalitat Valenciana for a Grisolia fellowship (GRISOLIA 2012/015)