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.

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 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

Synthesis of functionalized pyrazole derivatives by regioselective [3+2] cycloadditions of N-Boc-α-amino acid-derived ynones

2018 ◽  
Vol 73 (7) ◽  
pp. 467-480 ◽  
Author(s):  
Eva Pušavec Kirar ◽  
Uroš Grošelj ◽  
Amalija Golobič ◽  
Franc Požgan ◽  
Sebastijan Ričko ◽  
...  
Keyword(s):  
Amino Acids ◽  
Nuclear Magnetic Resonance ◽  
Amino Acid ◽  
Ring Opening ◽  
Pyrazole Derivatives ◽  
X Ray Diffraction ◽  
X Ray ◽  
Acid Catalyzed ◽  
Azomethine Imines

Abstract [3+2] cycloadditions of ynones derived from glycine and (S)-alanine and some other dipolarophiles with azomethine imines, nitrile oxides, diazoacetate, and azidoacetate were studied. The dipolarophiles were obtained from α-amino acids, either by the reduction of the carboxy function with ethynylmagnesium bromide or by propiolation of the amino function. Cu-catalyzed cycloadditions of ynones to azomethine imines were regioselective and gave the expected cycloadducts as inseparable mixtures of diastereomers. In some instances, further oxidative hydrolytic ring-opening took place to afford 3,3-dimethyl-3-(1H-pyrazol-1-yl)propanoic acids. Acid-catalyzed cycloadditions of 3-butenone were also regioselective and provided mixtures of diastereomeric cycloadducts, which were separated by chromatography. In the reactions of title ynones with alkyl diazoacetates, in situ-formed benzonitrile oxides, and tert-butyl azidoacetate, all cycloadducts were obtained as single regioisomers. The structures of all novel compounds were established by nuclear magnetic resonance and X-ray diffraction.

ChemInform Abstract: Non-Lewis Acid Catalyzed Epoxide Ring Opening with Amino Acid Esters.

ChemInform ◽  
2009 ◽  
Vol 40 (40) ◽  
Author(s):  
Christine Philippe ◽  
Thierry Milcent ◽  
Benoit Crousse ◽  
Daniele Bonnet-Delpon
Keyword(s):  
Amino Acid ◽  
Lewis Acid ◽  
Ring Opening ◽  
Epoxide Ring ◽  
Amino Acid Esters ◽  
Epoxide Ring Opening ◽  
Acid Catalyzed ◽  
Acid Esters

First Stereoselective Synthesis of (6R,7R,8S)-8-Chlorogoniodiol

Synthesis ◽  
2017 ◽  
Vol 49 (11) ◽  
pp. 2483-2487 ◽  
Author(s):  
Ambati Sharada ◽  
Kundeti Rao ◽  
Jhillu Yadav ◽  
Tadikamalla Rao ◽  
Kommu Nagaiah
Keyword(s):  
Ring Opening ◽  
Stereoselective Synthesis ◽  
Asymmetric Epoxidation ◽  
Cinnamyl Alcohol ◽  
Linear Sequence ◽  
12 Steps ◽  
Ring Opening Of Epoxide ◽  
Key Steps ◽  
Sharpless Asymmetric Epoxidation ◽  
Barbier Allylation

A stereoselective synthesis of (6R,7R,8S)-8-chlorogoniodiol has been achieved in a linear sequence of 12 steps and 19.8% overall yield from cinnamyl alcohol. The key steps include Sharpless asymmetric epoxidation, regioselective ring opening of epoxide, indium-mediated Barbier allylation, and Still–Gennari olefination.

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