Ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o-NosylOXY): a recyclable coupling reagent for racemization-free synthesis of peptide, amide, hydroxamate, and ester.
Ubiquitousness of amide and ester functionality makes coupling reactions extremely important. Although numerous coupling reagents are available, methods of preparation of the common and efficient reagents are cumbersome. Those reagents generate a substantial amount of chemical waste and lack recyclability. Ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o-NosylOXY), the first member of a new generation of coupling reagents, produces byproducts that can be easily recovered and reused for the synthesis of the same reagent, making the method more environmentally friendly and cost-effective. The synthesis of amides, hydroxamates, peptides, and esters using this reagent is described. The synthesis of the difficult sequences, for example, the islet amyloid polypeptide (22-27) fragment (with a C-terminal Gly, H-Asn-Phe-Gly-Ala-Ile-Leu-Gly-NH2) and acyl carrier protein (65-74) fragment (H-Val-Gln-Ala-Ala-Ile-Asp-Tyr-Ile-Asn-Gly-OH), following the solid-phase peptide synthesis (SPPS) protocol and Amyloid β (39-42) peptide (Boc-Val-Val-IIe-Ala-OMe), following solution-phase strategy is demonstrated. Remarkable improvement is noticed with respect to reaction time, yield, and retention of stereochemistry. A mechanistic investigation and recyclability are also described.
Department of Chemistry, Indian Institute of Technology Guwahati , Guwahati, Assam 781039, India.
Dharm
D
Dev
Nani Babu
NB
Palakurthy
Kishore
K
Thalluri
Jyoti
J
Chandra
Bhubaneswar
B
Mandal
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D004952:Esters; D009574:Nitro Compounds / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism
D000577:Amides; D000596:Amino Acids; D000682:Amyloid; D016229:Amyloid beta-Peptides; D004952:Esters; D009574:Nitro Compounds; D010455:Peptides; C000593429:ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate