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

2020 ◽  
Author(s):  
Zi-You Tian ◽  
HUA LU
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Ring Opening ◽  
Biomedical Applications ◽  
Functional Group ◽  
Ring Opening Polymerization ◽  
High Yield ◽  
Synthetic Polypeptides ◽  
Acid Catalyzed ◽  
Hydroxyl Acid

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

2020 ◽  
Author(s):  
Zi-You Tian ◽  
HUA LU
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Ring Opening ◽  
Biomedical Applications ◽  
Functional Group ◽  
Ring Opening Polymerization ◽  
High Yield ◽  
Synthetic Polypeptides ◽  
Acid Catalyzed ◽  
Hydroxyl Acid

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

scholarly journals A moisture-tolerant route to unprotected α/β-amino acid N-carboxyanhydrides and facile synthesis of hyperbranched polypeptides

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zi-You Tian ◽  
Zhengchu Zhang ◽  
Shuo Wang ◽  
Hua Lu
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Protein Modification ◽  
Water Soluble ◽  
Ring Closure ◽  
High Yield ◽  
Side Chain ◽  
Facile Synthesis ◽  
Synthetic Polypeptides ◽  
Acid Catalyzed

AbstractA great hurdle in the production of synthetic polypeptides lies in the access of N-carboxyanhydrides (NCA) monomers, which requires dry solvents, Schlenk line/gloveboxe, and protection of side-chain functional groups. Here we report a robust method for preparing unprotected NCA monomers in air and under moisture. The method employs epoxy compounds as ultra-fast scavengers of hydrogen chloride to allow assisted ring-closure and prevent NCA from acid-catalyzed decomposition under moist conditions. The broad scope and functional group tolerance of the method are demonstrated by the facile synthesis of over 30 different α/β-amino acid NCAs, including many otherwise inaccessible compounds with reactive functional groups, at high yield, high purity, and up to decagram scales. The utility of the method and the unprotected NCAs is demonstrated by the facile synthesis of two water-soluble polypeptides that are promising candidates for drug delivery and protein modification. Overall, our strategy holds great potential for facilitating the synthesis of NCA and expanding the industrial application of synthetic polypeptides.

scholarly journals Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

2016 ◽  
Vol 12 ◽  
pp. 1765-1771 ◽  
Author(s):  
Pramod R Markad ◽  
Navanath Kumbhar ◽  
Dilip D Dhavale
Keyword(s):  
Amino Acid ◽  
Allyl Alcohol ◽  
Ring Opening ◽  
Functional Group ◽  
Asymmetric Epoxidation ◽  
Oxirane Ring ◽  
Trimethyl Borate ◽  
Pyranose Ring ◽  
Acid Catalyzed ◽  
Sharpless Asymmetric Epoxidation

The C8’-epimeric pyranosyl amino acid core 2 of amipurimycin was synthesized from D-glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective β-glycosylation afforded the pyranosyl thymine nucleoside 2 – a core of amipurimycin.

Biodegradable copolymers based on poly(ethylene oxide), polylactide and polydepsipeptide sequences with functional groups

e-Polymers ◽  
2001 ◽  
Vol 1 (1) ◽  
Author(s):  
Yakai Feng ◽  
Doris Klee ◽  
Hartwig Höcker
Keyword(s):  
Block Copolymers ◽  
Ethylene Oxide ◽  
Aspartic Acid ◽  
Functional Groups ◽  
Ring Opening ◽  
Ring Opening Polymerization ◽  
Biodegradable Copolymers ◽  
Protective Groups ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

AbstractFor the purpose of increasing the hydrophilicity of polylactide, new block copolymers with protected functional groups, poly(lactide-co-(S)-b-benzyl aspartate)-poly(ethylene oxide)-poly(lactide-co-(S)- b-benzyl aspartate), were synthesized via ring-opening polymerization of D,L-lactide and (3S, 6R,S)-3- [(benzyloxycarbonyl)methyl]-6-methylmorpholine-2,5-dione in the presence of hydroxyltelechelic poly(ethylene oxide) (PEO) as an initiator at 140 °C for 24 h. The benzyl protective groups of the block copolymers were completely removed to give poly(lactide-co-(S)-aspartic acid)-PEO-poly(lactide-co-(S)-aspartic acid), (poly(DLLA-co-Asp)-b-PEO-b-poly(DLLA-co-Asp)). This shows lower crystallization and melting temperature compared with the polymers before deprotection. Poly(DLLA-co-Asp)-b-PEO-b-poly(DLLA-co-Asp) with 55.6 wt.-% of PEO is more hydrophilic, shows higher water absorption and is degraded faster than with 39.5 wt.-% of PEO.

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