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The potential of “customizable units” to generate structural diversity for biological screenings is highlighted in this proof‐of‐concept synthesis of new peptides related to the potent antitumoral Sansalvamide A. Using L‐4‐hydroxyproline (Hyp) as a customizable unit in a linear parent peptide, an improved procedure for selective peptide modification was developed. A divergent Hyp scission‐reductive amination process was carried out, affording five linear peptides with cationic residues, and notably, an N‐alkyl moiety that affected the conformation of the peptide. After two steps (saponification and macrocyclization), sixteen differently N1‐substituted linear and cyclic peptides were obtained. For the first time, the activity of the linear and cyclic compounds was compared. Not only some linear analogs but also cyclic compounds with scarcely studied cationic residues were active against MCF7 breast cancer line. Thus, the structural diversity generated from customizable units can be valuable in drug discovery., This work was partly financed by the Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico) through project 2015‐01‐807, and by MINECO‐MCIU (Spain) with European Social Funds (ESF), through Programme Plan Estatal I+D‐RETOS (project SAF‐2013‐48399‐R). C. J. S. received a postdoctoral contract from the Torres Quevedo Programme (PTQ15‐07923) by MINECO/Min. Science and Innovation, cofinanced by BIOSIGMA SL. Finally, I.R−E. and F.C. thank CONACYT for Catedra contract 942 and predoctoral grant 305283 respectively.

The selective manipulation of Hyp customizable units in DKP substrates allows the generation of a rigid scaffold with four tailor‐made chains which are spatially‐orientated. The key step is a domino radical scission‐oxidation process which allows the generation of N‐substituted DKPs. The versatility of this methodology to produce scaffolds in high optical purity for material and drug discovery is described herein., This work was partly financed by project APOGEO (Cooperation Program INTERREG‐MAC 2014–2020, with European Funds for Regional Development‐FEDER) and by projects SAF‐2013‐48399‐R, Plan Estatal I+D‐RETOS (MINECO‐MCIU)‐European Social Funds (ESF) and CONACYT 2015–01‐807 (CONACYT‐Mexico)

An efficient conversion of hydroxyproline >customizable> units into new amino acids with a variety of N-alkyl substituents is described. The process is versatile and can afford valuable N-methyl amino acids and N,O-acetals. In addition, it allows the introduction of N-homoallylic substituents and N-chains with terminal ester, ketone, or cyano groups. These chains could be used for peptide extension or conjugation to other molecules (e.g., by olefin metathesis, peptide ligation, etc.). The transformation is carried out in just two (for R = CHOAc) or three steps (scission of the pyrrolidine ring, manipulation of the α-chain, and the N-substituent) under mild, metal-free conditions, affording products with high optical purity., This work was supported by the Research Program SAF-2013-48399-R, Plan Estatal de I+D, Ministerio de Economía, Industria, y Competitividad, Spain (currently Ministerio de Ciencia, Innovación y Universidades) and European Social Funds (FSE). D.H. thanks her current contract financed by Cabildo de Tenerife, included in Tenerife 2030 under the Program TF INNOVA 2016-21 (with MEDI & FDCAN Funds). C.J.S. was the recipient of a postdoctoral contract from the Torres Quevedo Programme (PTQ15-07923), and C.C. was granted a contract from the Doctorados Industriales Programme (DI-14-06736). Both industrial Programmes were sponsored by MINECO-Ministerio de Ciencia, Innovación y Universidades, and cofinanced by the company BIOSIGMA SL (Spain)., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Trabajo presentado en el 1st Molecules Medicinal Chemistry Symposium, celebrado en Barcelona (España) el 8 de septiembre de 2017., Libraries of compounds containing unnatural amino acids or amino acid analogues were prepared from inexpensive substrates using sustainable processes. The compounds were evaluated for antimicrobial activity against different pathogens

Our site-selective modification of serine or threonine units in peptides allows the generation of β-substituted dehydroamino acids, which increase peptide resistance to hydrolysis and may improve their biological properties. Both the terminal and internal positions can be modified, and different customizable units can be activated separately. Remarkably, high Z selectivity is achieved, even at internal positions. The conversion involves a one-pot oxidative radical scission/phosphorylation process by using the low-toxicity (diacetoxyiodo)benzene/iodine system as the scission reagent. The resulting α-amino phosphonates undergo a Horner-Wadsworth-Emmons reaction to produce the dehydroamino acid derivatives (in a Z/E ratio of usually >98:2) under mild and metal-free conditions., This work was supported by the Research Program SAF‐2013‐48399‐R, Plan Estatal de I+D, Ministerio de Economía. Industria y Competitividad, Spain, and European Social Funds (FSE). D.H. and C.J.S. thank CSIC (Spanish Research Council) and Gobierno de Canarias, respectively, for their research contracts. D.H. also acknowledges her current contract financed by Cabildo de Tenerife, Program TF INNOVA 2016‐21 (with MEDI & FDCAN Funds).

Las transformaciones a nivel global de los sistemas financieros se tradujeron en cambios regionales de las entidades financieras y modificaron la relación entre el sector financiero y no-financiero, la cual se encuentra determinada por las funciones del crédito, que en caso de Italia, dependen fundamentalmente de su demanda interna, y que a nivel regional tienen un papel importante en relación con el sistema financiero de la zona euro.

The site-selective modification of small peptides at a glutamate residue allows the ready preparation of α,γ-hybrids. In this way, a single peptide can be transformed into a variety of hybrid derivatives. The process takes place under very mild conditions, and good global yields are obtained., This work was supported by the Research Program CTQ2009-07109 of the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Ciencia e Innovación/Economía y Competitividad, Spain. We also acknowledge financial support from FEDER funds. C.J.S. thanks ACIISI(Gobierno de Canarias) for a predoctoral fellowship

The one-pot transformation of α-amino acid into β-amino acid derivatives is described. The application of this method to the synthesis of modified dipeptides was also illustrated.

The one-pot radical fragmentation–phosphorylation reaction of α-amino acids and β-amino alcohols affords α-amino phosphonates in good yields. The reaction was applied to the synthesis of potentially bioactive phosphonates.

The present method is applied to preparation of small peptide derivatives with β-aldehyde moieties which in turn are precursors of peptides possessing a γ-alcohol unit.

The selective conversion of serine or threonine units of di- and tripeptides into substituted dehydroamino acids is reported. Thus, these common α-amino acids undergo a scission-phosphorylation process to give α-amino phosphonate residues. A Horner-Wadsworth-Emmons reaction with aldehydes or ketones follows to afford the final products with excellent Z-stereoselectivity (Z:E > 98:2). In this way, a single peptide precursor can selectively be transformed into a variety of derivatives., This work was supported by the Research Program CTQ2009-07109 of the Plan Nacional de I+D, Ministerio de Ciencia e Innovación (currently Economía y Competitividad), Spain, and European Regional Development Funds (FEDER). C.J.S. thanks Gobierno de Canarias for a predoctoral grant

A direct method for the transformation of α-amino acids into β-amino aldehydes was developed, and applied to the modification of the C-terminal residue of peptides. The method takes place in good yields and under mild conditions. The application of this methodology to the preparation of small peptides with γ-amino alcohol units, which are precursors of analogues of peptaibol antibiotics, is also described., This work was supported by the Research Projects CTQ2006-14260/PPQ and CTQ2009-07109 of the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Educación y Ciencia (MEC) and Ministerio de Ciencia e Innovación (MICINN), Spain. We also acknowledge financial support from FEDER funds. C.J.S. thanks the Gobierno de Canarias for a predoctoral fellowship.

Short α,β,α-tripeptides comprising a central chiral trisubstituted β 2,2,3*-amino acid residue form unusual γ-turns and δ-turns in CDCl 3 and DMSO-d 6 solutions but do not form β-turns. Thermal coefficients of backbone amide protons, 2D-NMR spectra, and molecular modeling revealed that these motifs were strongly dependent on the configuration (chiral effect) of the central β-amino acid residue within the triad. Accordingly, SSS tripeptides adopted an intraresidual γ-turn like (C6) arrangement in the central β-amino acid, whereas SRS diastereomers preferred an extended δ-turn (C9) conformation. A different SRS-stabilizing bias was observed in the crystal structures of the same compounds, which shared the extended δ-turn (C9) found in solution, but incorporated an additional extended β-turn (C11) to form an overlapped double turn motif., We thank the Gobierno Vasco (Project SAIOTEK S-PR10BF02) and Ministerio de Ciencia e Innovación (Project CTQ2009-07109) for financial support and SGIker UPV/EHU for NMR facilities. C.J.S. thanks Gobierno de Canarias for a predoctoral fellowship.

A direct method for the transformation of α-amino acids into β-amino aldehydes or 2-acetoxyazetidines is described. This work was applied to the modification of peptides.

11 páginas, 2 figuras, 6 tablas, 3 esquemas., The one-pot conversion of readily available alpha-amino acid into beta-amino acid derivatives was carried out in good yields. The method is a sequential process initiated by a tandem radical decarboxylation-oxidation reaction; the resulting acyliminium ion was trapped by silyl ketenes. Stoichiometric and catalytic versions of this reaction were developed and then applied to prepare modified di- and tripeptides. Interestingly, some tripeptides formed expanded beta-turns in the solid state., This work was supported by the Investigation Programmes CTQ2006-14260/PPQ and PPQ2003-01379 of the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Educación y Ciencia and Ministerio de Ciencia y Tecnología, Spain. We also acknowledge financial support from FEDER funds. C.J.S. thanks the CSIC for an I3P contract, and the Gobierno de Canarias-BIOSIGMA SL for a research contract.

We have demonstrated that chemically modified anticancer drugs can provide random laser (RL) when infiltrated in a biological tissue. A fluorescent biomarker has been covalently bound to tamoxifen, which is one of the most frequently used drugs for breast cancer therapy. The light emitted by the drug-dye composite is scattered in tissue, which acts as a gain medium. Both non-coherent and coherent RL regimes have been observed. Moreover, the analysis of power Fourier transforms of coherent RL spectra indicates that the tissues show a dominant random laser cavity length of about 18 µm, similar to the average size of single cells. These results show that RL could be obtained from other drugs, if properly marked with a fluorescent tag, which could be appealing for new forms of combined opto-chemical therapies.

The discovery of genotoxic amino acids derived from phenylglycine, and possessing halogen substituents, is described. The utility of hypervalent iodine reagents in the synthesis of this class of compounds is highlighted. The mechanism of action of the (haloaryl)glycines was studied in Saccharomyces cerevisiae.

The synthesis and liquid crystalline properties of a new series of diacylhydrazine derivatives (2a-g) are reported. All compounds of series 2 exhibit a smectic C (SmC) phase. The first homologues (2a, 2b) display a monotropic SmC mesophase, whereas the highest homologues (2c-g) exhibit an enantiotropic SmC phase. The liquid crystalline properties were investigated by differential scanning calorimetry, polarizing optical microscopy and X-ray measurements.