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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).

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.

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.

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.