Amino Triazolo Diazepines (Ata) as Constrained Histidine Mimics

Buysse, Koen; Farard, Julien; Nikolaou, Alexandros; Vanderheyden, Patrick; Vauquelin, Georges; Pedersen, Daniel Sejer; Tourwé, Dirk; Ballet, Steven

doi:10.1021/ol202767k

Cited by 38 publications

(32 citation statements)

References 35 publications

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“…By employing 4 mol‐% of [RuCl 2 Cp*] x with THF as the solvent, triazole 1 was obtained in 96 % yield after heating to 100 °C for 20 min in a microwave reactor; these conditions allowed the separation problems encountered earlier to be circumvented. This set of conditions provides a great improvement relative to previously reported routes to similar compounds 20,21. The regiochemistry of 1,5‐disubstituted triazole 1 was confirmed by 2D NOESY (see Supporting Information).…”

Section: Resultsmentioning

confidence: 69%

“…On the other hand, the much less studied 1,5‐substituted triazoles, prepared by ruthenium‐catalyzed reaction of an organic azide with an alkyne,19 could provide an alternative with a flexible enough backbone to adopt several conformations. Byusse et al have reported the synthesis of a bicyclic peptidomimetic compound containing a 1,5‐disubstituted 1,2,3‐triazole,20 whereas Appella and co‐workers have employed a similar unit to induce a turn in a peptoid oligomer 21. However, applications of the ruthenium‐catalyzed cycloaddition reaction in this context are still rare and further work is needed to develop suitable building blocks and synthetic methods within this area.…”

Section: Introductionmentioning

confidence: 99%

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δ‐Peptides from RuAAC‐Derived 1,5‐Disubstituted Triazole Units

et al. 2014

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Non‐natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ‐peptides, consisting of n units of a 1,5‐disubstituted 1,2,3‐triazole amino acid (5Tzl). The monomer was prepared using ruthenium‐catalyzed azide–alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp*]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X‐D functional. These data indicate that several conformations may co‐exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo‐5Tzl may prove essential for mimicking natural peptides composed of α‐amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds.

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Section: Resultsmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

δ‐Peptides from RuAAC‐Derived 1,5‐Disubstituted Triazole Units

et al. 2014

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“…This results in the formation of triazolyl amino acid ester 113 , which on hydrogenolysis undergoes cyclization to give chiral fused triazoles 116 . Via second route, 112 b reacts with 111 to give azide‐alkyne products 114 that undergoes intramolecular cycloaddition to form desired products 116 …”

Section: Synthesis Of Chiral Fused 123‐triazolesmentioning

confidence: 99%

Chiral Fused 1,2,3‐Triazoles: A Synthetic Overview

2020

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Triazoles have always occupied a pivotal position in the field of medicinal and pharmaceutical chemistry. Recently, the area of chiral fused triazoles has gained attention. The synthetic routes to access chiral fused triazole may involve either a natural or synthetic chiral starting material with a suitably functionalized azide and alkyne component or isomer resolution to achieve chirality. Asymmetric synthesis methods using chiral complexes and organocatalysis have also emerged for obtaining chiral fused triazoles. Herein, we have described an up-to-date overview of different synthetic protocols applied to construct chiral fused 1,2,3-triazoles. Scheme 1. Basic methodologies for triazole construction. 2 3 4 5 6 7 8 . Yanai's stereo-divergent synthesis of ido-triazole ent-6 a and gluco-triazoles 7 a. Scheme 3. Yanai's diastereo-divergent synthesis of manno-, gulo-, galacto-and altro-triazoles. . Konda's synthesis of tricyclic triazolo-oxazepines 62. Scheme 15. Cobb's synthesis of spirocyclic triazolooxazine nucleosides 67. Scheme 16. Sen's synthesis of tetracyclic triazolo-oxazepines 69. to azide group and protected amine was propargylated to access azido-alkynes 122 c-h for triazole formation 124 (Scheme 29). The copper catalyzed version of this step was also carried out that gave almost approximately same yields in lesser Scheme 25. Chrandrasekaran's synthesis of triazolo-pyrazines and pyrazinones from amino acid derived sulfamidates. Scheme 26. Chrandrasekaran's synthesis of triazolo-pyrazinone 110 having pendant amino acid.structural features of triazoles, the authors carried out one pot hydrogenation and insitu Boc-protection of 155 a, followed by azidation and propargylation to afford azido-alkyne 160. Subsequently, thermal azide-alkyne cycloaddition furnished the triazole product 161 in good yield (Scheme 34).Allenyl silanes are extensively used in synthetic organic transformations and provide ready access to enantiopure pyrroles, oxiranes, furans and vinyl silanes. In lewis acid assisted reaction, allenyl silanes work as propargyl anion equivalents. Allenyl silane forms regioselective homopropargylic alcohol when treated with aldehyde and ketone. The stabilization is Scheme 31. Thomas's synthesis of steroidal fused 1,2,3-triazoles.Scheme 32. Thomas's synthesis of steroidal fused NH-1,2,3-triazoles and steroidal 4,5-fused triazolo-alkynes.

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“…A tandem Ugi‐4CR followed by thermal Huisgen cyclisation was applied to design a library of aminotriazolodiazepine di‐ and tripeptides of type 55 by starting from Boc‐β‐azidoalanine ( 54 ; Scheme ). These reactions were typically high‐yielding (up to 94 %) and operationally simple (one‐pot, two‐step) and offered considerable improvements in terms of yield and efficiency over previous routes to these molecules, which employed RuAAC in combination with lactamisation . This came at the expense of losing stereocontrol at the newly created stereogenic centre.…”

Section: Application Of Aac Reactions For the Synthesis Of Small (mentioning

confidence: 99%

“…These reactions were typically high-yielding (up to 94 %) and operationally simple (one-pot, two-step) and offered considerable improvements in terms of yield and efficiency over previous routes to these molecules, which employed RuAAC in combination with lactamisation. [35] This came at the expense of losing stereocontrol at the newly created stereogenic centre. Eight-membered rings are generally considered to be one of the most difficult ring sizes to obtain, but Barlow and co-workers were also recently able to apply these conditions to the synthesis of eight-membered, triazole-fused lactams of type 58.…”

Section: Application Of Aac Reactions For the Synthesis Of Small (Fromentioning

confidence: 99%

Cyclisation To Form Small, Medium and Large Rings by Use of Catalysed and Uncatalysed Azide–Alkyne Cycloadditions (AACs)

2017

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This microreview briefly summarises recent developments in cyclisation to afford small, medium and large rings (five to 30 members) by way of both catalysed and uncatalysed azide–alkyne cycloaddition (AAC). The standard AAC reactions – intramolecular Huisgen, CuAAC and RuAAC – are presented, as well as some of their contemporary variations. In addition, we present useful strategies for overcoming common problems encountered in these reactions.

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Amino Triazolo Diazepines (Ata) as Constrained Histidine Mimics

Cited by 38 publications

References 35 publications

δ‐Peptides from RuAAC‐Derived 1,5‐Disubstituted Triazole Units

δ‐Peptides from RuAAC‐Derived 1,5‐Disubstituted Triazole Units

Chiral Fused 1,2,3‐Triazoles: A Synthetic Overview

Cyclisation To Form Small, Medium and Large Rings by Use of Catalysed and Uncatalysed Azide–Alkyne Cycloadditions (AACs)

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