143327-83-7

Usage

Uses

Used in Pharmaceutical Synthesis:
Carbamic acid, (1-ethynyl-3-methylbutyl)-, 1,1-dimethylethyl ester, (S)(9CI) is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its unique structure and reactivity make it suitable for the development of new drugs and therapeutic agents.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, Carbamic acid, (1-ethynyl-3-methylbutyl)-, 1,1-dimethylethyl ester, (S)- (9CI) serves as a valuable research tool. It is used to study the structure-activity relationships of carbamic acid derivatives and to explore their potential applications in drug discovery and development.
Used in Drug Development:
Carbamic acid, (1-ethynyl-3-methylbutyl)-, 1,1-dimethylethyl ester, (S)(9CI) is employed in the development of new drugs targeting specific diseases and conditions. Its unique properties and reactivity contribute to the design and synthesis of novel therapeutic agents with improved efficacy and selectivity.
Used in Chemical Synthesis Processes:
Carbamic acid, (1-ethynyl-3-methylbutyl)-, 1,1-dimethylethyl ester, (S)(9CI) is also used in various chemical synthesis processes, where its reactivity and functional groups can be exploited to produce a wide range of chemical products. Its versatility makes it a valuable asset in the field of organic chemistry.

Upstream product

• 58521-45-2 tert-butoxycarbonyl-L-leucinal 
• 27491-70-9 dimethyl diazomethylphosphonate 
• 91254-81-8 (1-Formyl-3-methylbutyl)carbamic acid,1,1-dimethylethyl ester 
• 90965-06-3 dimethyl 1-(1-diazo-2-oxopropyl)phosphonate 
• 5927-18-4 trimethyl phosphonoacetate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 4202-14-6 dimethyl (2-oxopropyl)phosphonate 
• 87694-50-6 N-(tert-butoxycarbonyl)-L-leucine-N'-methoxy-N'-methylamide 

Downstream Products

• 1357007-69-2 C₃₄H₅₃N₇O₄ 
• 1357007-98-7 C₃₄H₅₃N₇O₄ 
• 1357007-97-6 C₂₉H₄₆N₄O₃ 
• 1357008-51-5 C₃₄H₅₄N₄O₅ 
• 1357007-96-5 C₂₃H₃₅N₃O₂ 
• 1357008-50-4 C₂₈H₄₃N₃O₄ 
• 1357007-68-1 C₃₃H₅₁N₇O₄ 
• 1357007-92-1 C₃₃H₅₁N₇O₄ 
• 1265146-01-7 C₂₈H₃₃NO₃ 
• 1265146-00-6 C₃₃H₄₄N₂O₅ 
• 1265145-90-1 C₃₃H₄₆N₂O₆ 
• 1262483-16-8 C₂₇H₃₈N₂O₄ 

Relevant academic research and scientific papers

Development of a functional cis-prolyl bond biomimetic and mechanistic implications for nickel superoxide dismutase

During recent years several peptide-based Ni superoxide dismutase (NiSOD) models have been developed. These NiSOD models show an important structural difference compared to the native NiSOD enzyme, which could cause a completely different mechanism of superoxide dismutation. In the native enzyme the peptide bond between Leu4 and Pro5 is cis-configured, while the NiSOD models exhibit a trans-configured peptide bond between these two residues. To shed light on how the configuration of this single peptide bond influences the activity of the NiSOD model peptides, a new cisprolyl bond surrogate was developed. As surrogate we chose a leucine/alanine-based disubstituted 1,2,3-triazole, which was incorporated into the NiSOD model peptide replacing resi-dues Leu4 and Pro5. The yielded 1,5disubstituted triazole nickel peptide exhibited high SOD activity, which was approximately the same activity as its parent trans-configured analogue. Hence, the conformation of the prolyl peptide bond apparently has of minor importance for the catalytic activity of the metallopeptides as postulated in literature. Furthermore, it is shown that the triazole metallopeptide is forming a stable cyanide adduct as a substrate analogue model complex.

Semi-synthesis of biologically active nisin hybrids composed of the native lanthionine ABC-fragment and a cross-stapled synthetic DE-fragment

The antimicrobial peptide nisin is a promising template for designing novel peptide-based antibiotics to improve its drug-like properties. First steps in that direction represent the synthesis of hybrid nisin derivatives that contain a native nisin ABC-part and synthesized cross-stapled DE-ring fragments and are described here. The biological activity of the newly synthesized nisin derivatives was evaluated in order to compare the bioactivity of the synthetic DE-ring containing mimic and native lanthionine-bridged DE-ring containing nisin. The native nisin ABC-ring system was obtained via chymotrypsin digestion of full-length nisin, and was subsequently functionalized at the C-terminal carboxylate with two different amino alkyne moieties. Next, nisin hybrids were successfully prepared using Cu(I)-catalyzed azide alkyne cycloaddition 'click' chemistry by chemo-selective ligation of the ABC-alkyne with the N-terminal azido functionalized dicarba-DE ring mimic. The newly synthesized compounds were active as potent lipid II binders and retained antimicrobial activity in a growth inhibition assay. However, pore formation was not observed, possibly either due to the different character of the 'staples' as compared to the parent sulfides, or due to the triazole moiety as a sub-optimal amide bond isostere.

1,5-Disubstituted 1,2,3-Triazole-Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Peptidotriazolamers are hybrid foldamers combining features of peptides and triazolamers—repetitive peptidomimetic structures with triazoles replacing peptide bonds. We report on the synthesis of a new class of peptidomimetics, containing 1,5-disubstituted 1,2,3-triazoles in an alternating fashion with amide bonds and the analysis of their conformation in solid state and solution. Homo- or heterochiral peptidotriazolamers were obtained from enantiomerically pure propargylamines with stereogenic centers in the propargylic position and α-azido esters by ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC) under microwave conditions in high yields. With such building blocks the peptidotriazolamers are readily available by solution phase synthesis. While the conformation of the homochiral peptidotriazolamer Boc-Ala[5Tz]Phe-Val[5Tz]Ala-Leu[5Tz]Val-OBzl resembles that of a β VIa1 turn, the heterochiral peptidotriazolamer Boc-d-Ala[5Tz]Phe-d-Val[5Tz]Ala-d-Leu[5Tz]Val-OBzl adopts a polyproline-like repetitive structure.

Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues

A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.

Synthesis of 3′-triazoyl-dinucleotides as precursors of stable Phe-tRNAPhe and Leu-tRNALeu analogues

We report here the synthesis of stable Phe-tRNAPhe and Leu-tRNALeu analogues containing a 1,2,3-triazole ring instead of the ribose-amino acid ester bond. The 1,2,3-triazole ring is generated by dipolar cycloaddition of alkyne Phe and Leu analogues to 3′-azido-3′- deoxyadenosine via the CuI-catalysed Huisgen, Meldal, Sharpless 1,3-cycloaddition. The corresponding triazoyl pdCpA dinucleotides, obtained by classical phosphoramidite chemistry, were enzymatically ligated to 22-nt or 74-nt RNA generating stable Phe-tRNAPhe analogues containing the acceptor stem or full tRNA moieties, respectively. These molecules represent useful tools to study the contribution of the RNA and amino acid moieties in stabilization of aminoacyl-tRNA/protein complexes.

Synthesis of 3′-triazoyl-dinucleotides as precursors of stable Phe-tRNAPhe and Leu-tRNALeu analogues

We report here the synthesis of stable Phe-tRNAPhe and Leu-tRNALeu analogues containing a 1,2,3-triazole ring instead of the ribose-amino acid ester bond. The 1,2,3-triazole ring is generated by dipolar cycloaddition of alkyne Phe and Leu analogues to 3′-azido-3′-deoxyadenosine via the CuI-catalysed Huisgen, Meldal, Sharpless 1,3-cycloaddition. The corresponding triazoyl pdCpA dinucleotides, obtained by classical phosphoramidite chemistry, were enzymatically ligated to 22-nt or 74-nt RNA generating stable Phe-tRNAPhe analogues containing the acceptor stem or full tRNA moieties, respectively. These molecules represent useful tools to study the contribution of the RNA and amino acid moieties in stabilization of aminoacyl-tRNA/protein complexes.

1,2,3-Triazoles as amide bond mimics: Triazole scan yields protease-resistant peptidomimetics for tumor targeting

The triazole makes the difference: Replacement of amide bonds in the backbone of peptides by 1,4-disubstituted 1,2,3-triazole isosteres affords peptidomimetics with retained receptor affinity and cell-internalization properties, enhanced proteolytic stability, and improved tumor-targeting capabilities. Copyright

Synthesis of sansalvamide A peptidomimetics: Triazole, oxazole, thiazole, and pseudoproline containing compounds

Peptidomimetic-based macrocycles typically have improved pharmacokinetic properties over those observed with peptide analogs. Described are the syntheses of 13 peptidomimetic derivatives that are based on active sansalvamide A structures, where these analogs incorporate heterocycles (triazoles, oxazoles, thiazoles, or pseudoprolines) along the macrocyclic backbone. The syntheses of these derivatives employ several approaches that can be applied to convert a macrocyclic peptide into its peptidomimetic counterpart. These approaches include peptide modifications to generate the alkyne and azide for click chemistry, a serine conversion into an oxazole, a Hantzsch reaction to generate the thiazole, and protected threonine to generate the pseudoproline derivatives. Furthermore, we show that two different peptidomimetic moieties, triazoles, and thiazoles, can be incorporated into the macrocyclic backbone without reducing cytotoxicity: triazole and thiazole.

Universal peptidomimetics

This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.

Pyrrole-based scaffolds for turn mimics

Two amino acid derived synthons were combined to give homopropargylic amines 2. Platinum dichloride was used to cyclize these intermediates into pyrroles 3 which collapsed to the target secondary structure mimics 1 on treatment with base. Side chains of these compounds overlay with an idealized type 1 β-turn and with an inverse γ-turn.(Figure Presented)