Peptide Coupling Reagents, More than a Letter Soup Ayman El-Faham* and Fernando Albericio* Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028-Barcelona, Spain Alexandria University, Faculty of Science, Department of Chemistry, P.O. Box 426, Ibrahimia, 21321 Alexandria, Egypt CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028-Barcelona, Spain. Department of Organic Chemistry, University of Barcelona, Martí i Franqu es 1-11, 08028-Barcelona, Spain

Peptide coupling reagents, more than a letter soup

Albert Isidro-Llobet, Mercedes Alvarez,* and Fernando Albericio* Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain; Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain; and Department of Organic Chemistry, University of Barcelona, Marti i Franques 1, 08028 Barcelona, Spain Received April 28, 2008

/pdf/amino-acid-protecting-groups-w29zg5z6oi.pdf

Amino Acid-Protecting Groups

A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics

Today, Fmoc SPPS is the method of choice for peptide synthesis. Very-high-quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/psc.2836

Advances in Fmoc solid‐phase peptide synthesis

Emerging single atom catalysts (SACs), especially carbon-based SACs are appealing materials in environmental catalysis because of their ultrahigh performances, environmental friendliness, structural/chemical robustness, and the maximum utilization of active metal sites. The metal centres, carbon matrixes, and coordination characteristics collectively determine the electronic features of carbon-based SACs, and their behaviours in catalysing peroxide activation and efficiencies in advanced oxidation processes (AOPs). However, there is lack of a comprehensive and critical review reporting the successful marriage of carbon-based SACs in AOP-based remediation technologies. It is particularly necessary to systematically compare and reveal the catalytic sites and the associated mechanisms of carbon-based SACs in diverse AOP systems. In this review, we highlight the synthetic strategies, characterisation, and computation of carbon-based SACs, and for the first time, showcase their innovative applications in AOP technologies. We unveil the origins of versatile catalytic oxidation pathways in different AOP systems and the mechanisms of micropollutant degradation over carbon-based SACs, distinguished from the upsized counterparts (metals/oxides and carbon substrates). We also provide directions to the rational design of on-demand SACs for green chemistry and environmental sustainability. Also, we suggest a designated and integrated experimental/theoretical protocol for revealing the structure-catalysis relations of SACs in AOP applications, and propose the prospects for future opportunities and challenges.

Single-atom catalysis in advanced oxidation processes for environmental remediation.

Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.

/pdf/thiopeptide-antibiotics-retrospective-and-recent-advances-fwsfd5zgjk.pdf

Thiopeptide Antibiotics: Retrospective and Recent Advances

ConspectusReductive electron transfer (ET) to organic compounds is a powerful method for the activation of substrates via the formation of radicals, radical anions, anions, and dianions that can be exploited in bond-cleaving and bond-forming processes. Since its introduction to the synthetic community in 1977 by Kagan, SmI2 has become one of the most important reducing agents available in the laboratory. Despite its widespread application in aldehyde and ketone reduction, it was widely accepted that carboxylic acid derivatives could not be reduced by SmI2; only recently has our work led to this dogma being overturned, and the reduction of carboxylic acid derivatives using SmI2 can now take its place alongside aldehyde/ketone reduction as a powerful activation mode for synthesis. In this Account, we set out our studies of the reduction of carboxylic acid derivatives using SmI2, SmI2–H2O, and SmI2–H2O–NR3 and the exploitation of the unusual radical anions that are now accessible in unprecedented carbon–carb...

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

Biaryls are ubiquitous core structures in drugs, agrochemicals and organic materials that have profoundly improved many aspects of our society. Although traditional cross-couplings have made practical the synthesis of many biaryls, C–H arylation represents a more attractive and cost-effective strategy for building these structural motifs. Furthermore, the ability to install biaryl units in complex molecules via late-stage C–H arylation would allow access to valuable structural diversity, novel chemical space and intellectual property in only one step. However, known C–H arylation protocols are not suitable for substrates decorated with polar and delicate functionalities, which are commonly found in molecules that possess biological activity. Here we introduce a class of ruthenium catalysts that display a unique efficacy towards late-stage arylation of heavily functionalized substrates. The design and development of this class of catalysts was enabled by a mechanistic breakthrough on the Ru(ii)-catalysed C–H arylation of N–chelating substrates with aryl (pseudo)halides, which has remained poorly understood for nearly two decades. Nearly two decades after its discovery, the Ru(II)-catalysed C–H arylation of N-chelating aromatics with aryl halides was reinvestigated and a new key reaction intermediate was uncovered. A thorough mechanistic elucidation has now led to the development of a new class of catalysts with unique efficacy towards late-stage arylation of ‘real-world’ compounds.

Cyclometallated ruthenium catalyst enables late-stage directed arylation of pharmaceuticals

The recent development of thiopeptide analogues of antibiotics has allowed some of the limitations inherent to these naturally occurring substances to be overcome. Chemical synthesis, semisynthetic derivatization, and engineering of the biosynthetic pathway have independently led to complementary modifications of various thiopeptides. Some of the new substances have displayed improved profiles, not only as antibiotics, but also as antiplasmodial and anticancer drugs. The design of novel molecules based on the thiopeptide scaffold appears to be the only strategy to exploit the high potential they have shown in vitro. Herein we present the most relevant achievements in the production of thiopeptide analogues and also discuss the way the different approaches might be combined in a multidisciplinary strategy to produce more sophisticated structures.

Thiopeptide engineering: a multidisciplinary effort towards future drugs.

The thiopeptide antibiotic baringolin has been synthesized, and its structure and stereochemistry have been confirmed. The use of a strategy based on palladium-catalyzed cross-couplings permitted a modular construction of this natural product.

Xavier Just-Baringo

Papers

Thiopeptide Antibiotics: Retrospective and Recent Advances

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

Cyclometallated ruthenium catalyst enables late-stage directed arylation of pharmaceuticals

Thiopeptide engineering: a multidisciplinary effort towards future drugs.

Total Synthesis and Stereochemical Assignment of Baringolin