Nucleophilic reactivity of peptides toward 2-acyloxy-N-ethylbenzamides. Utility of free peptides as nucleophiles in amide bond forming reactions

1974 ◽  
Vol 39 (19) ◽  
pp. 2831-2835 ◽  
Author(s):  
D. S. Kemp ◽  
Zmira W. Bernstein ◽  
George N. McNeil
Keyword(s):  
Amide Bond ◽  
Bond Forming ◽  
Bond Forming Reactions ◽  
Nucleophilic Reactivity

scholarly journals Minimizing HCN in DIC/Oxyma-Mediated Amide Bond-Forming Reactions

2020 ◽  
Vol 24 (7) ◽  
pp. 1341-1349 ◽  
Author(s):  
Marion Erny ◽  
Marika Lundqvist ◽  
Jon H. Rasmussen ◽  
Olivier Ludemann-Hombourger ◽  
Frédéric Bihel ◽  
...  
Keyword(s):  
Amide Bond ◽  
Bond Forming ◽  
Bond Forming Reactions

Are Aminomethyl Thioesters Viable Intermediates in Native Chemical Ligation Type Amide Bond Forming Reactions?

2018 ◽  
Vol 71 (9) ◽  
pp. 697
Author(s):  
Carlie L. Charron ◽  
Jade M. Cottam Jones ◽  
Craig A. Hutton
Keyword(s):  
Amide Bond ◽  
Native Chemical Ligation ◽  
Direct Reaction ◽  
Chemical Ligation ◽  
Bond Forming ◽  
Type Process ◽  
Bond Forming Reactions ◽  
Subsequent Conversion ◽  
Three Component Coupling

The condensation of N-mercaptomethyl amines and thioesters is a potential route to amides, via aminomethyl thioester intermediates, in a native chemical ligation type process followed by self-cleavage of the ‘mercaptomethyl’ auxiliary. This paper describes investigations towards the preparation of aminomethyl thioesters, and subsequent conversion into amides, from a three-component coupling of formaldehyde, a thioacid, and an amine. Our studies suggest that while such intermediates may be formed en route to amides, no advantages are offered over the direct reaction of the amine and thioacid precursors.

scholarly journals Minimizing HCN in DIC/Oxyma Mediated Amide Bond Forming Reactions

2020 ◽  
Author(s):  
Marion Erny ◽  
Marika Lundqvist ◽  
Jon H. Rasmussen ◽  
Olivier Ludemann-Hombouger ◽  
Frédéric Bihel ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Peptide Synthesis ◽  
Hydrogen Cyanide ◽  
Reaction Rate ◽  
Solid Support ◽  
Amide Bond ◽  
Prussic Acid ◽  
Bond Forming ◽  
H Nmr ◽  
Bond Forming Reactions

<p>Aiming at advancing protocols for safer, environmentally sensible peptide synthesis we report our findings with regards to the occurrence of hydrogen cyanide (HCN, prussic acid) in amide bond forming reactions mediated by diisopropylcarbodiimide (DIC) and ethyl (hydroxyimino)cyanoacetate (Oxyma). We have determined that HCN is always formed in amide bond forming reactions on solid support in N,N-dimethylformamide (DMF) when employing DIC/Oxyma. In an attempt to minimize the formation of prussic acid by means of preventing the linear DIC/Oxyma adduct <b>2</b> from cyclizing to oxadiazole <b>3</b> and in turn releasing HCN, we evaluated a series of greener solvents such as N-butylpyrrolidinone (NBP), NBP/ethyl acetate (EtOAc, 1:1), methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate (PolarClean, PC), and PC/EtOAc (1:1). We found that the ratio between <b>2</b> and <b>3</b> greatly depends on the solvent used and consequently, we further examined DMF, NBP, NBP/EtOAc (1:1) and NBP/EtOAc (1:4) as solvents for DIC/Oxyma mediated amidations on solid support and in solution. We found that using carboxylic acid/Oxyma/DIC in a 1:1:1 ratio the rate of HCN formation decreases in the following order DMF>NBP>NBP/EtOAc (1:1)>NBP/EtOAc (1:4) while the reaction rate increases in order of DMF~NBPin situ scavenging of the HCN formed. We carried out DIC/Oxyma mediated amidation of Fmoc-Gly-OH + (S)-(-)-1-phenylethylamine in DMF-d<sub>7</sub> with 0, 5 and 10 equiv of dimethyl trisulfide (DMTS) as HCN scavenger. The formation of HCN and rate of amidation was monitored by <sup>1</sup>H NMR, revealing that DMTS scavenges HCN without inhibiting the rate of amidation. DIC/Oxyma mediated amidations of Fmoc‑Ser(<i>t</i>‑Bu)‑OH with (S)-(‑)-1-phenylethylamine in DMF and NBP/EtOAc (1:4) with and without 10 equiv of DMTS were carried out and found to be comparable.</p>

scholarly journals Minimizing HCN in DIC/Oxyma Mediated Amide Bond Forming Reactions

2020 ◽  
Author(s):  
Marion Erny ◽  
Marika Lundqvist ◽  
Jon H. Rasmussen ◽  
Olivier Ludemann-Hombouger ◽  
Frédéric Bihel ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Peptide Synthesis ◽  
Hydrogen Cyanide ◽  
Reaction Rate ◽  
Solid Support ◽  
Amide Bond ◽  
Prussic Acid ◽  
Bond Forming ◽  
H Nmr ◽  
Bond Forming Reactions

<p>Aiming at advancing protocols for safer, environmentally sensible peptide synthesis we report our findings with regards to the occurrence of hydrogen cyanide (HCN, prussic acid) in amide bond forming reactions mediated by diisopropylcarbodiimide (DIC) and ethyl (hydroxyimino)cyanoacetate (Oxyma). We have determined that HCN is always formed in amide bond forming reactions on solid support in N,N-dimethylformamide (DMF) when employing DIC/Oxyma. In an attempt to minimize the formation of prussic acid by means of preventing the linear DIC/Oxyma adduct <b>2</b> from cyclizing to oxadiazole <b>3</b> and in turn releasing HCN, we evaluated a series of greener solvents such as N-butylpyrrolidinone (NBP), NBP/ethyl acetate (EtOAc, 1:1), methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate (PolarClean, PC), and PC/EtOAc (1:1). We found that the ratio between <b>2</b> and <b>3</b> greatly depends on the solvent used and consequently, we further examined DMF, NBP, NBP/EtOAc (1:1) and NBP/EtOAc (1:4) as solvents for DIC/Oxyma mediated amidations on solid support and in solution. We found that using carboxylic acid/Oxyma/DIC in a 1:1:1 ratio the rate of HCN formation decreases in the following order DMF>NBP>NBP/EtOAc (1:1)>NBP/EtOAc (1:4) while the reaction rate increases in order of DMF~NBPin situ scavenging of the HCN formed. We carried out DIC/Oxyma mediated amidation of Fmoc-Gly-OH + (S)-(-)-1-phenylethylamine in DMF-d<sub>7</sub> with 0, 5 and 10 equiv of dimethyl trisulfide (DMTS) as HCN scavenger. The formation of HCN and rate of amidation was monitored by <sup>1</sup>H NMR, revealing that DMTS scavenges HCN without inhibiting the rate of amidation. DIC/Oxyma mediated amidations of Fmoc‑Ser(<i>t</i>‑Bu)‑OH with (S)-(‑)-1-phenylethylamine in DMF and NBP/EtOAc (1:4) with and without 10 equiv of DMTS were carried out and found to be comparable.</p>

scholarly journals Orthogonal coiled coils enable rapid covalent labelling of two distinct membrane proteins with peptide nucleic acid barcodes

2021 ◽  
Author(s):  
Georgina C Gavins ◽  
Katharina Gröger ◽  
Marc Reimann ◽  
Michael D. Bartoschek ◽  
Sebastian Bultmann ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Membrane Proteins ◽  
Peptide Nucleic Acid ◽  
Coiled Coils ◽  
Amide Bond ◽  
Bond Forming ◽  
Bond Forming Reactions ◽  
Distinct Membrane

Templated chemistry offers the prospect of addressing specificity challenges occurring in bioconjugation reactions. Here, we show two peptide-templated amide-bond forming reactions that enable the concurrent labelling of two different membrane...

Recent Advances on C-Se Bond-forming Reactions at Low and Room Temperature

2020 ◽  
Vol 23 (28) ◽  
pp. 3206-3225 ◽  
Author(s):  
Amol D. Sonawane ◽  
Mamoru Koketsu
Keyword(s):  
Room Temperature ◽  
Bond Formation ◽  
Bond Forming ◽  
Material Chemistry ◽  
Recent Advances ◽  
Bond Forming Reactions ◽  
Bond Formation Reactions

: Over the last decades, many methods have been reported for the synthesis of selenium- heterocyclic scaffolds because of their interesting reactivities and applications in the medicinal as well as in the material chemistry. This review describes the recent numerous useful methodologies on C-Se bond formation reactions which were basically carried out at low and room temperature.

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