We thank Dr. John Greaves and Ms. Soroosh Sorooshian, Department of Chemistry, University of California, Irvine Mass Spectrometry Facility, for mass spectrometric analyses. We also thank Mr. Jacob Buchanan for helpful discussions, as well as Miss Stephanie J. Conn, Mrs. Shannon M. Huffman (Vreeland), and Miss Alexandra N. Wexler for early stage work on this project. Partial funding was provided by the Central Washington University (CWU) School of Graduate Studies (C.E.M), the CWU Seed Grant Program, and the CWU Faculty Research Program.

<ol>
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The authors have nothing to declare.

Los esfuerzos iniciales para preparar clavatadine A alistaron un enfoque tradicional, indirecta a guanidinylation partir de un precursor de amina adecuado, que en este caso era una azida terminal. Fundamental para este esfuerzo fue la unión de las dos mitades de la molécula para construir el resto carbamato. Desafortunadamente, todos los intentos de realizar una reducción de la azida en previsión de una guanidinylation de la última etapa planificada no tuvieron éxito. 25,26 Estos retrocesos inspirados l...

El objetivo de este video es mostrar cómo el uso de un método guanidinylation directa y pronto para hacer una estructura terminal de guanidina es más práctico, rápido y eficiente que los métodos tradicionales guanidinylation en síntesis orgánica. El grupo funcional de guanidina, se encuentra en el aminoácido arginina, es un elemento estructural fundamental en muchos productos naturales complejos y productos farmacéuticos. El descubrimiento y diseño de nuevos guanidina que contiene productos naturales y moléculas pequeñas establecen la necesidad de un método guanidinylation más eficiente. El enfoque utilizado comúnmente tortuosa cuenta con la introducción de un precursor de guanidina latente que se desenmascara en una etapa tardía de la síntesis. En contraste, una táctica sencillo instala una guanidina protegida en una amina primaria a principios de una ruta sintética. La naturaleza reactiva de guanidinas generalmente les impide el uso rutinario sin una estrategia de grupo protector adecuado. Tradicionalmente, los métodosPara añadir un grupo funcional de guanidina involucrado un enfoque indirecto que implicó múltiples etapas de protección, seguido de la adición de la guanidina al final de la síntesis. Dos síntesis recientes ilustran los inconvenientes inherentes a 1,2 guanidinylation indirecta. El método directo informado en el presente documento implica la reacción de un reactivo de guanidina protegida con una amina primaria desde el principio en la síntesis de una molécula dada y después desproteger al final de la síntesis. Esta estrategia se ha implementado correctamente en la síntesis total reciente de alcaloides marinos biológicamente activos clavatadine A y phidianidine A y B 3,4. Si bien este método guanidinylation directa tiene sus ventajas sobre los métodos tradicionales de guanidinylation todavía tiene sus inconvenientes. Las condiciones químicas que la guanidina protegida puede sobrevivir dependerá del grupo protector empleado. A pesar de estos posibles inconvenientes, el método guanidinylation directa es una estrategia que permiteañadir guanidinas terminales de aminas primarias para su uso en la síntesis de moléculas orgánicas complejas.

<table><tbody><tr><td>Chloroform-d</td><td>Sigma-Aldrich</td><td>612200-100G</td><td>99.8% D, 0.05% v/v tetramethylsilane; Caution: toxic</td></tr><tr><td>Dimethylsulfoxide-d&lt;sub&gt;6&lt;/sub&gt;</td><td></td><td>185965-50G</td><td>99.9% D, 1% v/v tetramethylsilane</td></tr><tr><td>sodium thiosulfate pentahydrate</td><td>Sigma-Aldrich</td><td>S8503-2.5KG</td><td></td></tr><tr><td>sodium sulfate, anhydrous</td><td>Sigma-Aldrich</td><td>238597-2.5KG</td><td></td></tr><tr><td>silica gel</td><td>Fisher Scientific</td><td>S825-25</td><td>Merck, Grade 60, 230-400 mesh</td></tr><tr><td>washed sea sand</td><td>Sigma-Aldrich</td><td>274739-5KG</td><td></td></tr><tr><td>hexane</td><td>Sigma-Aldrich</td><td>178918-20L</td><td>Caution: flammable</td></tr><tr><td>ethyl acetate</td><td>Sigma-Aldrich</td><td>319902-4L</td><td></td></tr><tr><td>methylene chloride</td><td>Sigma-Aldrich</td><td>D65100-4L</td><td></td></tr><tr><td>sodium chloride</td><td>Sigma-Aldrich</td><td>S9888-10KG</td><td></td></tr><tr><td>sodium bicarbonate</td><td>Sigma-Aldrich</td><td>S6014-2.5KG</td><td></td></tr><tr><td>acetic acid</td><td>Sigma-Aldrich</td><td>695092-2.5L</td><td></td></tr><tr><td>hydrochloric acid</td><td>Sigma-Aldrich</td><td>258248-2.5L</td><td>Caution: Corrosive</td></tr><tr><td>bromine</td><td>Sigma-Aldrich</td><td>470864-50G</td><td>&gt;99.99% trace metals basis; Caution: Corrosive, causes severe burns</td></tr><tr><td>hydrobromic acid</td><td>Sigma-Aldrich</td><td>244260-500ML</td><td>48% aqueous; Caution: Corrosive</td></tr><tr><td>2,5-dimethoxyphenylacetic acid</td><td>ChemImpex</td><td>26909</td><td></td></tr><tr><td>chloroform</td><td>Sigma-Aldrich</td><td>132950-4L</td><td>Caution: Toxic</td></tr><tr><td>tetrahydrofuran</td><td>Sigma-Aldrich</td><td>360589-4x4L</td><td>Caution: highly flammable</td></tr><tr><td>&lt;em&gt;N,N&lt;/em&gt;-diisopropylethylamine</td><td>Sigma-Aldrich</td><td>D125806-500ML</td><td>Caution: Corrosive</td></tr><tr><td>triethylamine</td><td>Sigma-Aldrich</td><td>T0886-1L</td><td>Caution: Corrosive</td></tr><tr><td>3 Angstrom molecular sieves</td><td>Sigma-Aldrich</td><td>208574-1KG</td><td></td></tr><tr><td>calcium hydride</td><td>Sigma-Aldrich</td><td>213268-100G</td><td>Caution: Corrosive, reacts violently with water</td></tr><tr><td>ammonium molybdate</td><td>Sigma-Aldrich</td><td>431346-50G</td><td></td></tr><tr><td>phosphomolybdic acid</td><td>Sigma-Aldrich</td><td>221856-100G</td><td></td></tr><tr><td>cerium(IV) sulfate</td><td>Sigma-Aldrich</td><td>359009-25G</td><td></td></tr><tr><td>1-butanol</td><td>Sigma-Aldrich</td><td>537993-1L</td><td></td></tr><tr><td>1,4-butanediamine</td><td>Sigma-Aldrich</td><td>D13208-100G</td><td>Caution: Corrosive / warm in hot water bath to melt prior to use</td></tr><tr><td>triphosgene</td><td>VWR</td><td>200015-064</td><td>Caution: Highly Toxic</td></tr><tr><td>methanol</td><td>Sigma-Aldrich</td><td>646377-4X4L</td><td></td></tr><tr><td>sodium acetate</td><td>Sigma-Aldrich</td><td>241245-100G</td><td></td></tr><tr><td>Dimethylsulfoxide-d&lt;sub&gt;6&lt;/sub&gt;</td><td>Sigma-Aldrich</td><td>570672-50G</td><td>Anhydrous, 99.9% D</td></tr><tr><td>sodium hydroxide</td><td>Sigma-Aldrich</td><td>221465-500G</td><td>Caution: Corrosive</td></tr><tr><td>guanidine hydrochloride</td><td>Sigma-Aldrich</td><td>G4505-25G</td><td>Caution: Toxic, Corrosive</td></tr><tr><td>di-tert-butyl dicarbonate</td><td>VWR</td><td>200002-018%</td><td>Caution: Toxic / may warm in hot water bath to melt prior to use</td></tr><tr><td>trifluoromethanesulfonic anhydride</td><td>Fisher Scientific</td><td>50-206-771</td><td>98%, anhydrous; Caution: toxic, corrosive, extremely moisture sensitive</td></tr></tbody></table>

a direct, early stage guanidinylation protocol for the synthesis of complex aminoguanidine-containing natural products

El grupo funcional de guanidina, que se muestra más prominente en el aminoácido arginina, uno de los pilares fundamentales de la vida, es un elemento estructural importante que se encuentra en muchos productos naturales complejos y productos farmacéuticos. Debido al continuo descubrimiento de nuevos productos naturales que contiene guanidina-y pequeñas moléculas diseñadas, métodos rápidos y eficientes guanidinylation son de gran interés para los químicos orgánicos sintéticos y medicinales. Debido a que el nucleófilo y basicidad de guanidinas pueden afectar transformaciones químicas posteriores, tradicional guanidinylation, indirecto es típicamente perseguido. Los métodos indirectos emplean comúnmente múltiples etapas de protección que implican un precursor de amina latente, como una azida, ftalimida, o carbamato. Por eludir estos métodos tortuosos y empleando una reacción directa guanidinylation temprano en la secuencia sintética, fue posible para forjar el terminal de guanidina lineal que contiene columna vertebral de clavatadine A a darse cuentauna síntesis breve y simplificada de este factor inhibidor potente XI bis. En la práctica, el hidrocloruro de guanidina se elabora con una matriz de proteger cuidadosamente construida que está optimizado para sobrevivir a las etapas de síntesis para venir. En la preparación de clavatadine A, guanidinylation directa de una diamina comercialmente disponible eliminado dos pasos innecesarios de su síntesis. Junto con la gran variedad de grupos protectores de guanidina conocido, guanidinylation directa pone en evidencia un sentido práctico y eficiente sucinta inherentes a los métodos que encuentran un hogar en la caja de herramientas de un químico sintético.

Guanidinylation directa de un α disponible en el mercado, ω-diamina, seguido por reacción con trifosgeno, proporcionó el isocianato reactivo 8 como la parte lineal de clavatadine A (Figura 1b). Los rendimientos de esta secuencia de reacción de dos etapas son invariablemente alta, 95% o mayor. Reactivo Guanidinylation 6 se preparó exactamente como se describe por Goodman. 11,24 <p class="jove_content" fo:keep-together...

Watch this Scientific Journal Video about A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products at JoVE.com

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

Un directa, Protocolo Guanidinylation Etapa Temprana para la Síntesis de complejos productos naturales que contiene aminoguanidina-

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

a-direct-early-stage-guanidinylation-protocol-for-synthesis-complex

Universidad de Cartagena UDEC

Research

JoVE Journal

Chemistry

10.5K vistas.  Central Washington University. Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol. 

Video: A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development

The involvement of free radicals in life sciences has constantly increased with time and has been connected to several physiological and pathological processes. This subject embraces diverse scientific areas, spanning from physical, biological and bioorganic chemistry to biology and medicine, with applications to the amelioration of quality of life, health and aging. Multidisciplinary skills are required for the full investigation of the many facets of radical processes in the biological environment and chemical knowledge plays a crucial role in unveiling basic processes and mechanisms. We developed a chemical biology approach able to connect free radical chemical reactivity with biological processes, providing information on the mechanistic pathways and products. The core of this approach is the design of biomimetic models to study biomolecule behavior (lipids, nucleic acids and proteins) in aqueous systems, obtaining insights of the reaction pathways as well as building up molecular libraries of the free radical reaction products. This context can be successfully used for biomarker discovery and examples are provided with two classes of compounds: mono-trans isomers of cholesteryl esters, which are synthesized and used as references for detection in human plasma, and purine 5',8-cyclo-2'-deoxyribonucleosides, prepared and used as reference in the protocol for detection of such lesions in DNA samples, after ionizing radiations or obtained from different health conditions.

Radical-based biomimetic chemistry has been applied to building-up libraries necessary for biomarker development.

Radicales Libres en Biología Química: del comportamiento químico al desarrollo de biomarcadores

The involvement of free radicals in life sciences has constantly increased with time and has been connected to several physiological and pathological ...

Investigación

Química

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase

Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical probe that targets the enzyme&#39;s active sites. A reporter tag introduced into the probe allows for the detection of the labeled enzyme by in-gel fluorescence scanning, protein blot, fluorescence microscopy, or liquid chromatography-mass spectrometry. Here, we describe the preparation and use of the compound ARN14686, a click chemistry activity-based probe (CC-ABP) that selectively recognizes the enzyme N-acylethanolamine acid amidase (NAAA). NAAA is a cysteine hydrolase that promotes inflammation by deactivating endogenous peroxisome proliferator-activated receptor (PPAR)-alpha agonists such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). NAAA is synthesized as an inactive full-length proenzyme, which is activated by autoproteolysis in the acidic pH of the lysosome. Localization studies have shown that NAAA is predominantly expressed in macrophages and other monocyte-derived cells, as well as in B-lymphocytes. We provide examples of how ARN14686 can be used to detect and quantify active NAAA ex vivo in rodent tissues by protein blot and fluorescence microscopy.

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase

Here, we describe the preparation and use of an activity-based probe (ARN14686, undec-10-ynyl-N-[(3S)-2-oxoazetidin-3-yl]carbamate) that allows for the detection and quantification of the active form of the proinflammatory enzyme N-acylethanolamine acid amidase (NAAA), both in vitro and ex vivo.

Preparación y<em&gt; En Vivo</em&gt; El uso de una sonda basada en la actividad de<em&gt; N</em&gt; -acylethanolamine Ácido amidasa

Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical ...

Bioquímica

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this procedure amino functionalized 'lysine' and guanido functionalized 'arginine' peptoid monomers can be included within the same peptoid sequence. This procedure uses on-resin (N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) or Dde protection, orthogonal conditions to the Boc protection of lysine monomers. Subsequent deprotection allows an efficient on-resin guanidinylation reaction to form the arginine residues. The procedure is compatible with the commonly used submonomer method of peptoid synthesis, allowing simple peptoids to be made using common laboratory equipment and commercially available reagents. The representative synthesis, purification and characterization of two mixed peptoids is described. The evaluation of these compounds as potential anti-infectives in screening assays against Leishmania mexicana is also described. The protozoan parasite L. mexicana is a causative agent of cutaneous leishmaniasis, a neglected tropical disease that affects up to 12 million people worldwide.

A protocol to synthesize peptoids with mixed cationic functionality in the same sequence is presented (lysine- and arginine-type monomers). Subsequent testing of these compounds against Leishmania mexicana, the protozoan parasites that cause cutaneous leishmaniasis, is also described.

Un método eficaz para la síntesis de peptoides con monómeros de tipo mixto lisina / arginina del tipo y la evaluación de su actividad anti-Leishmania

This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this ...

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes &#945;v and &#945;5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (N&#969;) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N&#8242;-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

A protocol for the synthesis of alkyl-modified guanidines based on the use of the corresponding precursors is presented.

Modificación y funcionalización del grupo guanidina por Precursores adaptado

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. ...

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both &#945;-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.

Peptide tertiary amides (PTAs) are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. Here we describe a synthetic method which combines&#160;both split-and-pool and sub-monomer strategies to synthesize a one-bead one-compound library of PTAs.

Síntesis Split-y-piscina y caracterización del péptido Terciario Amida Biblioteca

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide sequences. Synthesis of some unnatural amino acids often includes the use of a precursor consisting of a Schiff-base stabilized by a nickel cation. Unnatural side-chains can be installed on an amino acid backbone found in this Schiff-base complex. The resulting unnatural amino acid can then be isolated from this complex using hydrolysis of the Schiff-base, typically by employing reflux in strongly acidic solution. These highly acidic conditions may remove acid-labile side-chain protecting groups necessary for the unnatural amino acids to be used in microwave-assisted solid-phase peptide synthesis. In this work, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff base complex. Hydrolysis conditions presented in this work are suitable for retention of acid-labile side-chain protecting groups and may be adaptable to a variety of unnatural amino acid substrates.

Here, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff-base complex. Hydrolysis conditions presented here are suitable for use when retention of acid-labile side-chain protecting groups is required. This technique may be adaptable to a variety of unnatural amino acid substrates.

Hidrólisis de un Ni-Schiff-base compleja usando condiciones adecuadas para la retención de los grupos protectores lábiles en medio ácido

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide ...

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles (PPAs) and Related Biomaterials

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). Traditional PAs possess charged amino acids as solubilizing groups (lysine, arginine), which are directly connected to a lipid segment or can contain a linker region made of neutral amino acids. Tuning the peptide sequence of PAs can yield diverse morphologies. Similarly, PPAs possess a hydrophobic segment and neutral amino acids, but also contain polyamine molecules as water solubilizing (hydrophilic) groups. As is the case with PAs, PPAs can also self-assemble into diverse morphologies, including small rods, twisted nano-ribbons, and fused nano-sheets, when dissolved in water. However, the presence of both primary and secondary amines on a single polyamine molecule poses a significant challenge when synthesizing PPAs. In this paper, we show a simple protocol, based on literature precedents, to achieve a facile synthesis of PPAs using solid phase peptide synthesis (SPPS). This protocol can be extended to the synthesis of PAs and other similar systems. We also illustrate the steps that are needed for cleavage from the resin, identification, and purification.

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials

The synthesis of polyamine-based peptide amphiphiles (PPAs) is a significant challenge due to the presence of multiple amine nitrogens, which requires judicious use of protecting groups to mask these reactive functionalities. In this paper, we describe a facile method for the preparation of these new class of self-assembling molecules.

Protocolo fácil para la síntesis de uno mismo-montaje base poliamina péptido Anfífilos (PPAs) y relacionados con biomateriales

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). ...

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and functionalize polymer chains with compounds that are able to improve biocompatibility, mechanical properties, or cell viability allows the design of novel materials to meet new challenges in the biomedical field. With the polymer functionalization strategies, click chemistry is a powerful tool to improve cell-compatibility and drug delivery properties of polymeric devices. Similarly, the fundamental need of biomedicine to use sterile tools to avoid potential adverse-side effects, such as toxicity or contamination of the biological environment, gives rise to increasing interest in the microwave-assisted strategy.
The combination of click chemistry and the microwave-assisted method is suitable to produce biocompatible hydrogels with desired functionalities and improved performances in biomedical applications. This work aims to synthesize RGD-functionalized hydrogels. RGD (arginylglycylaspartic acid) is a tripeptide that can mimic cell adhesion proteins and bind to cell-surface receptors, creating a hospitable microenvironment for cells within the 3D polymeric network of the hydrogels. RGD functionalization occurs through Huisgen 1,3-dipolar cycloaddition. Some PAA carboxyl groups are modified with an alkyne moiety, whereas RGD is functionalized with azido acid as the terminal residue of the peptide sequence. Finally, both products are used in a copper catalyzed click reaction to permanently link the peptide to PAA. This modified polymer is used with carbomer, agarose and polyethylene glycol (PEG) to synthesize a hydrogel matrix. The 3D structure is formed due to an esterification reaction involving carboxyl groups from PAA and carbomer and hydroxyl groups from agarose and PEG through microwave-assisted polycondensation. The efficiency of the gelation mechanism ensures a high degree of RGD functionalization. In addition, the procedure to load therapeutic compounds or biological tools within this functionalized network is very simple and reproducible.

We present a protocol for the synthesis of RGD-functionalized hydrogels as devices for cell and drug delivery. The procedure involves copper catalyzed alkyne-azide cycloaddition (CuAAC) between alkyne-modified polyacrylic acid (PAA) and a RGD-azide derivative. The hydrogels are formed using microwave-assisted polycondensation and their physicochemical properties are investigated.

La síntesis de hidrogeles funcionalizado-RGD como una herramienta para aplicaciones terapéuticas

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and ...

Bioingeniería

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very difficult and laborious to make aziridines in optically pure forms on a large scale to apply asymmetric synthesis of aza compounds. Fortunately, we successfully achieved both enantiomers (2R)- and (2S)-aziridine-2-carboxylates with the electron-donating &#945;-methylbenzyl group at the ring nitrogen as non-activated aziridines. These starting aziridines have two distinct functional groups-highly reactive three-membered ring and versatile carboxylate. They are applicable in ring-opening or ring-transformation with aziridine and in functional group transformation to others from carboxylate. Both of these enantiomers were utilized in the preparation of biologically important amino acyclic and/or aza-heterocyclic compounds in an asymmetric manner. Specifically, this report describes the first expedient asymmetric synthesis of both enantiomers of 5, 6-dihydrouracil-type marine natural products biemamide B and D as potential TGF-&#946; inhibitors. This synthesis consisted of regio- and the stereoselective ring-opening reaction of aziridine-2-carboxylate and subsequent formation of 4-aminoteterahydropyrimidine-2,4-dione. One more example in this protocol dealt a highly stereoselective Mukaiyama reaction of aziridine-2-carboxylate and silyl enol ether, following intramolecular aziridine ring-opening to provide easy and facile access to (-)-epiallo-isomuscarine.

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

In this study, we prepare both enantiomers of aziridine-2-carboxylate, which are used in the asymmetric synthesis of alkaloids, including biemamide B and D, and (-)-epiallo-isomuscarine.

Preparación de aziridinas no activadas enantiopure y síntesis de biemamida B, D y epiallo-isomuscarina

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very ...

Preparation of 1&deg; Amines: Azide Synthesis

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum hydride, or by catalytic hydrogenation to primary amines. The driving force for such reactions is the elimination of nitrogen gas.
Azide synthesis also works with other electrophiles like epoxides to produce amino alcohols through stereoselective ring-opening reactions. Alkyl azides have an explosive nature and must be carefully handled.

Preparation of 1&amp;deg; Amines: Azide Synthesis

Preparación de 1° Aminas: Síntesis de Azidas

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide ...