79410-35-8Relevant articles and documents
The evaluation of chiral benzosultams as auxiliaries in asymmetric azidation reaction
Ahn, Kyo Han,Kim, Seung-Ki,Ham, Chul
, p. 6321 - 6322 (1998)
Several chiral 3-substituted benzosultams, synthesized through an enantioselective Ru(II)-catalyzed transfer hydrogenation of corresponding sulfonylimines, are evaluated as chiral auxiliaries in the asymmetric azidation reaction of their N-acyl derivative
Topochemical Ene–Azide Cycloaddition Reaction
Khazeber, Ravichandran,Sureshan, Kana M.
supporting information, p. 24875 - 24881 (2021/09/22)
Topochemical reactions, high-yielding solid-state reactions arising from the proximal alignment of reacting partners in the crystal lattice, do not require solvents, catalysts, and additives, are of high demand in the context of green processes and enviro
Synthesis and Reversible Hydration of a Pseudoprotein, a Fully Organic Polymeric Desiccant by Multiple Single-Crystal-to-Single-Crystal Transformations
Mohanrao, Raja,Sureshan, Kana M.
supporting information, p. 12435 - 12439 (2018/09/10)
A diphenylalanine derivative, N3-Phe-Phe-NHCH2CCH, was designed for topochemical azide–alkyne cycloaddition (TAAC) polymerization. This dipeptide adopted β-sheet arrangement as designed, in its crystals, but the azide and alkyne were not fitly aligned for
Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics
Oueis, Emilia,Jaspars, Marcel,Westwood, Nicholas J.,Naismith, James H.
supporting information, p. 5842 - 5845 (2016/05/09)
The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.
A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds
Isidro-Llobet, Albert,Hadje Georgiou, Kathy,Galloway, Warren R. J. D.,Giacomini, Elisa,Hansen, Mette R.,Méndez-Abt, Gabriela,Tan, Yaw Sing,Carro, Laura,Sore, Hannah F.,Spring, David R.
supporting information, p. 4570 - 4580 (2015/04/14)
Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.
Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity
Proteau-Gagne, Arnaud,Rochon, Kristina,Roy, Melissa,Albert, Pierre-Julien,Guerin, Brigitte,Gendron, Louis,Dory, Yves L.
supporting information, p. 5267 - 5269 (2013/09/23)
Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-enkephalin is essential for the biological activity of the peptide.
A two-directional strategy for the diversity-oriented synthesis of macrocyclic scaffolds
O'Connell, Kieron M. G.,Beckmann, Henning S. G.,Laraia, Luca,Horsley, Helen T.,Bender, Andreas,Venkitaraman, Ashok R.,Spring, David R.
supporting information, p. 7545 - 7551 (2012/10/29)
Macrocyclic compounds represent a structural class with exceptional potential for biological activity; however, they have historically been underrepresented in screening collections and synthetic libraries. In this article we report the development of a highly step-efficient strategy for the diversity-oriented synthesis of complex macrocyclic architectures, using a modular approach based on the two-directional synthesis of bifunctional linear precursors and their subsequent combination in a two-directional macrocyclisation process. In this proof of principle study, the synthesis of 14 such compounds was achieved. Cheminformatic analysis of the compounds produced suggests that they reside in biologically relevant regions of chemical space and the compounds were screened for activity against two cancer cell lines.
A simple protocol for the synthesis of triazole-linked cyclic glycopeptidomimetics: A sequential Ugi-MCR and azide-alkyne cycloaddition approach
Samarasimhareddy,Hemantha, Hosahalli P.,Sureshbabu, Vommina V.
body text, p. 3104 - 3107 (2012/07/28)
Sequential combination of Ugi-MCR and click chemistry has been employed for the synthesis of triazole linked cyclic glycopeptidomimetics. The protocol employs Poc-amino alkyl isonitriles, sugar-1-amines, azido acids, and simple aldehydes as precursors. The dual nature of the propargyloxycarbonyl (Poc) group was explored for amine protection as well as cycloaddition with an azide. All the cyclic glycopeptidomimetics are isolated and characterized.
Diversity-oriented synthesis of macrocyclic peptidomimetics
Isidro-Llobet, Albert,Murillo, Tiffanie,Bello, Paula,Cilibrizzi, Agostino,Hodgkinson, James T.,Galloway, Warren R. J. D.,Bender, Andreas,Welch, Martin,Spring, David R.
scheme or table, p. 6793 - 6798 (2012/03/26)
Structurally diverse libraries of novel small molecules represent important sources of biologically active agents. In this paper we report the development of a diversity-oriented synthesis strategy for the generation of diverse small molecules based around a common macrocyclic peptidomimetic framework, containing structural motifs present in many naturally occurring bioactive compounds. Macrocyclic peptidomimetics are largely underrepresented in current small-molecule screening collections owing primarily to synthetic intractability; thus novel molecules based around these structures represent targets of significant interest, both from a biological and a synthetic perspective. In a proof-of-concept study, the synthesis of a library of 14 such compounds was achieved. Analysis of chemical space coverage confirmed that the compound structures indeed occupy underrepresented areas of chemistry in screening collections. Crucial to the success of this approach was the development of novel methodologies for the macrocyclic ring closure of chiral α-azido acids and for the synthesis of diketopiperazines using solid-supported N methylmorpholine. Owing to their robust and flexible natures, it is envisaged that both new methodologies will prove to be valuable in a wider synthetic context.
Benzotriazol-1-yl-sulfonyl azide for diazotransfer and preparation of azidoacylbenzotriazoles
Katritzky, Alan R.,El Khatib, Mirna,Bolshakov, Oleg,Khelashvili, Levan,Steel, Peter J.
experimental part, p. 6532 - 6539 (2010/12/19)
Benzotriazol-1-yl-sulfonyl azide, a new crystalline, stable, and easily available diazotransfer reagent provides N-(α-azidoacyl)benzotriazoles convenient for N-, O-, C- and S-acylations. The efficient syntheses of various amides, azido protected peptides, esters, ketones and thioesters is reported together with a wide range of azides (including α-azido acids from α- amino acids in partially aqueous conditions) and diazo compounds.
