A Robust, Open-Flask, Moisture-Tolerant, and Scalable Route to Unprotected α/β-Amino Acid N-Carboxyanhydrides

Synthetic polypeptides, commonly prepared by the ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCA), are a family of biomimetic materials with vast biomedical applications. A great hurdle in the pro-duction of synthetic polypeptides is the synthesis of NCA, which requires ultra-dry solvents, Schlenk line/gloveboxes, and the protection of sidechain functional groups. Herein, we report a robust and scalable new method for the production of unpro-tected NCA monomers in air and under moisture. The method employs propylene oxide or epichlorohydrin as an inexpensive and ultra-fast scavenger of hydrogen chloride to prevent NCA from acid-catalyzed decomposition under moist conditions. The broad scope and outstanding functional group tolerance of the method are demonstrated by the successful synthesis of more than 30 different NCAs, including many otherwise inaccessible compounds with reactive functional groups (e.g. hy-droxyl, thiol, and carboxylic acid), at high yield and up to ten-gram scale. The scope of the method can be further extended to various α-hydroxyl acid O-carboxyanhydrides (OCA) and β-amino acid NCAs (βNCA). Given these merits, our strategy holds great potential for revolutionizing the synthesis of NCA and polypeptides, and dramatically expanding the industrial application of synthetic polypeptides

A Robust, Open-Flask, Moisture-Tolerant, and Scalable Route to Unprotected α/β-Amino Acid N-Carboxyanhydrides

Synthetic polypeptides, commonly prepared by the ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCA), are a family of biomimetic materials with vast biomedical applications. A great hurdle in the pro-duction of synthetic polypeptides is the synthesis of NCA, which requires ultra-dry solvents, Schlenk line/gloveboxes, and the protection of sidechain functional groups. Herein, we report a robust and scalable new method for the production of unpro-tected NCA monomers in air and under moisture. The method employs propylene oxide or epichlorohydrin as an inexpensive and ultra-fast scavenger of hydrogen chloride to prevent NCA from acid-catalyzed decomposition under moist conditions. The broad scope and outstanding functional group tolerance of the method are demonstrated by the successful synthesis of more than 30 different NCAs, including many otherwise inaccessible compounds with reactive functional groups (e.g. hy-droxyl, thiol, and carboxylic acid), at high yield and up to ten-gram scale. The scope of the method can be further extended to various α-hydroxyl acid O-carboxyanhydrides (OCA) and β-amino acid NCAs (βNCA). Given these merits, our strategy holds great potential for revolutionizing the synthesis of NCA and polypeptides, and dramatically expanding the industrial application of synthetic polypeptides

Amination of β-hydroxyl acid esters via cooperative catalysis enables access to bio-based β-amino acid esters

β-amino acid esters are important scaffolds in medicinal chemistry and valuable building blocks for materials synthesis. Surprisingly, the waste-free construction of such moieties from readily available or renewable starting materials has not yet been addressed. Here we report on a robust and versatile method for obtaining β-amino acid esters by direct amination of β-hydroxyl acid esters via the borrowing hydrogen methodology using a cooperative catalytic system that comprises a homogeneous ruthenium catalyst and an appropriate Brønsted acid additive. This method allows for the direct amination of esters of 3-hydroxypropionic acid, a top value-added bio-based platform chemical, opening a simple route to access β-amino acid esters from a range of renewable polyols including sugars and glycerol.

Exploiting poly(α-hydroxy acids) for the acid-mediated release of doxorubicin and reversible inside–out nanoparticle self-assembly

Amphiphilic poly(hydroxyl acid) block copolymers are ideal candidates for the pH-responsive drug delivery via polymer degradation or polymer self-assembly/polymer disassembly.

Effect of Al content on number and location of hydroxyl acid species in zeolites: a DRIFTS quantitative protocol without the need for molar extinction coefficients

Collidine is able to interact only with hydroxyl species on the external surface or at the pore mouth of the zeolite as it is not able to access the internal pore structure.

The mechanistic role of catalytic residues in non-stereo dehalogenase (DehE)

Introduction: DehE or non-stereospecific dehalogenase from Rhizobium sp. RC1 catalyzes the hydrolytic dehalogenation of both isomers of D,L-2-haloacids to produce an inverted configuration of 2-hydroxyl acid. The enzymatic degradation for the removal of halides from haloacid substance has been highlighted since the enzyme itself is a potential candidate as bio-remediation agent. However, the mechanistic role of active site residues for dehalogenase is still unclear, especially for non-stereospecific ones. Method: In this study, using computational analysis, the complex structure of DehE docked with catalytic water (DehE-H2O) was subjected to MD simulation to study the mechanistic role of catalytic residues, especially Asn114 and Asp189 towards catalytic water. Results: Our findings confirmed that Asn114 hold the catalytic water at distance of ~4 Å while Asp189 was appropriately oriented towards catalytic water for catalysis reaction throughout the simulation process. Conclusions: The results attained here will play important role in elucidating the direct attack mechanism of halogenated compound by non-stereospecific haloacid dehalogenase. Moreover, this research could suggest different solvent that can be used in dehalogenation to produce a beneficial product other than hydroxyl acid.