Kishore Thalluri

Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate-mediated Lossen rearrangement: single-pot racemization-free synthesis of hydroxamic acids and ureas from carboxylic acids.

Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY) mediated Lossen rearrangement and its application for the synthesis of ureas is demonstrated. Required hydroxamic acids for the Lossen rearrangements were synthesized from carboxylic acids using the same reagent. Finally, reaction of an amine with the produced isocyanate resulted in urea. Good yields without racemization were achieved under milder and simpler reaction conditions. Reactions are compatible with common N-protecting groups, such as Boc, Fmoc, Cbz, and benzyl, as well as various OH protecting groups, such as (t)Bu and Bzl. Conversion from carboxylic acid to urea is achieved in one pot. Most importantly, byproducts Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] and 4-nitrobenzenesulfonic acid can be recovered easily and can be recycled to prepare the reagent. Thus, the method is environmentally friendly and cost-effective.

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.

Waste reduction in amide synthesis by a continuous method based on recycling of the reaction mixture

In this article, a new one pot synthesis of amides is demonstrated. Potential of the recovery and reuse strategy for waste reduction is examined. Finally, a new strategy is proposed where the whole reaction mixture containing the catalyst, the solvent (auxiliary) and the unreacted starting material is recovered by precipitating the product using ethanol and reused for the next cycle in a continuous operation protocol.

Amyloid β derived switch-peptides as a tool for investigation of early events of aggregation: a combined experimental and theoretical approach

Alzheimers disease, a severe neurodegenerative disorder, is believed to be caused by the interneuronal aggregation of the amyloid β peptide. It has no cure yet. Despite rigorous research, the mechanism of aggregation is not yet fully delineated. Especially probing the early events of the aggregation is difficult as we have no control on the kinetics of the process of aggregation. We have used amyloid β derived switch-peptides that behave as the functional mimic of the amyloid β peptide, and demonstrated that side chain aromatic interactions precede the β-sheet formation resulting in fibrillization. Detailed investigation into the early events of aggregation has become possible as the kinetics of aggregation of the switch-peptides can be controlled. We have used ultraviolet (UV) spectroscopy, circular dichroism (CD), Raman spectroscopy and Molecular Dynamics (MD) simulation as a combined experimental and theoretical approach.

Microwave assisted chemoselective organocatalytic peptide alcohol synthesis from C-terminal amide

The synthesis of peptide alcohols from peptides bearing C-terminal amide using β-aminoalcohols is achieved by a simple, efficient, racemization-free (<1.5%), and chemoselective transformation in the presence of cost-effective PTSA (para-toluenesulfonic acid) under microwave irradiation. Peptide alcohols can be synthesized by a standard solid phase peptide synthesis protocol obviating the need for specially designed resin.