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Chemical Reviews Mar 2012
Review
Topics: Animals; Aziridines; Cyclopropanes; Enzymes; Epoxy Compounds; Humans
PubMed: 22017381
DOI: 10.1021/cr200073d -
Chemistry, An Asian Journal Aug 2017An efficient approach towards peptide synthesis that allows easy access to variety of small peptides via one-pot aziridine-mediated ligation/desulfurization strategy has...
An efficient approach towards peptide synthesis that allows easy access to variety of small peptides via one-pot aziridine-mediated ligation/desulfurization strategy has been described. The protocol afforded a library of phenylalanine- and tryptophan-containing α-peptides in good yields by regioselective ring-opening of aziridine-3-aryl-2-carboxylates with peptide thioacids, followed by desulfurization.
Topics: Aziridines; Chemistry Techniques, Analytical; Peptide Library; Peptides; Phenylalanine; Stereoisomerism; Tryptophan
PubMed: 28544471
DOI: 10.1002/asia.201700538 -
Macromolecular Rapid Communications Mar 2014A switch from carbanions to aza-anions is performed by the addition of N-tosylaziridine (TAz) to living poly(styryl) (PS) chains. This is the first example of...
A switch from carbanions to aza-anions is performed by the addition of N-tosylaziridine (TAz) to living poly(styryl) (PS) chains. This is the first example of carbanionic aziridine ring-opening which was previously activated by amidation with a tosyl group to enable nucleophilic ring-opening by the living chain end. Poly(styrene)-tosylaziridines (PS-TAz) with narrow molecular weight distributions and variable molecular weights are synthesized. The removal of the tosyl group and subsequent functionalization is shown, evidencing quantitative transfer to azaanionic species. All polymers are characterized in detail by (1) H NMR spectroscopy, DOSY (1) H NMR spectroscopy, and size exclusion chromatography (SEC). This strategy allows the introduction of amine groups via anionic polymerization in analogy to the well-established epoxide termination.
Topics: Anions; Aziridines; Chromatography, Gel; Hydrolysis; Magnetic Resonance Spectroscopy; Polymerization; Polystyrenes
PubMed: 24497197
DOI: 10.1002/marc.201300860 -
The Journal of Organic Chemistry Aug 2018Aziridine aldehyde-driven macrocyclization of peptides is a powerful tool for the construction of biologically active macrocycles. While this process has been used to...
Aziridine aldehyde-driven macrocyclization of peptides is a powerful tool for the construction of biologically active macrocycles. While this process has been used to generate diverse collections of cyclic molecules, its mechanistic underpinnings have remained unclear. To enable progress in this area we have carried out a mechanistic study, which suggests that the cyclization owes its efficiency to a combination of electrostatic attraction between the termini of a nitrilium ion intermediate and intramolecular hydrogen bonding. Our model adequately explains the experimentally observed trends, including diastereoselectivity, and should facilitate the development of other macrocyclization reactions.
Topics: Aldehydes; Aziridines; Cyclization; Models, Chemical; Models, Molecular; Molecular Conformation; Peptides; Thermodynamics
PubMed: 29966423
DOI: 10.1021/acs.joc.8b01198 -
Organic Letters Apr 2022Copper catalyzed regioselective and stereospecific coupling between aziridines and generated pyridine Grignard reagents is reported. This method provides...
Copper catalyzed regioselective and stereospecific coupling between aziridines and generated pyridine Grignard reagents is reported. This method provides β-pyridylethylamines with diverse structures and functionalities from aziridines and iodopyridines. β-Pyridylethylamines are potential scaffolds for the synthesis of biologically active compounds often found in pharmaceuticals. The synthesis of challenging chiral dihydroazaindoles was also achieved through mild one-pot reaction conditions via aziridine opening followed by nucleophilic cyclization.
Topics: Aziridines; Catalysis; Copper; Molecular Structure; Stereoisomerism
PubMed: 35377668
DOI: 10.1021/acs.orglett.2c00703 -
Organic & Biomolecular Chemistry Aug 2015We describe herein the synthesis of aziridine-containing amino acids embedded within tripeptide structures. A range of amine nucleophiles have been shown to open the...
We describe herein the synthesis of aziridine-containing amino acids embedded within tripeptide structures. A range of amine nucleophiles have been shown to open the aziridine amino acid regioselectively at the β-position under mild conditions and without the requirement for a catalyst, forming new adducts in the process. Amino acid N-termini (or an N-containing sidechain) also served as effective nucleophiles for such aziridines and this concept could be extended to encompass a di- or tripeptide nitrogen as a nucleophile, thus providing new methodology for linking together peptide strands using an amine linker.
Topics: Amines; Aziridines; Catalysis; Peptides; Stereoisomerism
PubMed: 26166551
DOI: 10.1039/c5ob00856e -
Journal of the American Chemical Society Dec 2011A synthesis of aziridine-containing peptides via the Cu(II)-promoted coupling of unprotected peptide thioacids and N-H aziridine-2-carbonyl peptides is reported. The...
A synthesis of aziridine-containing peptides via the Cu(II)-promoted coupling of unprotected peptide thioacids and N-H aziridine-2-carbonyl peptides is reported. The unique reactivity of the resulting N-acylated aziridine-2-carbonyl peptides facilitates their subsequent regioselective and stereoselective nucleophilic ring-opening to give unprotected peptides that are specifically modified at the ligation site. The aziridine-mediated peptide ligation concept is exemplified using H(2)O as the nucleophile, producing a Xaa-Thr linkage (where Xaa can be an epimerizable and hindered amino acid). The overall process is compatible with a variety of unprotected amino acid functionality, most notably the N-terminal and Lys side chain amines.
Topics: Aziridines; Peptides
PubMed: 22112239
DOI: 10.1021/ja207133t -
The Journal of Organic Chemistry Feb 2021A broad range of -carbamoylaziridines were obtained and then treated by the diethyl phosphonate anion to afford α-methylene--bisphosphonate aziridines. Study of the...
A broad range of -carbamoylaziridines were obtained and then treated by the diethyl phosphonate anion to afford α-methylene--bisphosphonate aziridines. Study of the reaction's scope and additional experiments indicates that the transformation proceeds via a new mechanism involving the chelation of lithium ion. This last step is crucial for the reaction to occur and disfavors the aziridine ring-opening. A phosphonate-phosphate rearrangement from a α-hydroxybisphosphonate aziridine intermediate is also proposed for the first time. This reaction provides a simple and convenient method for the synthesis of a highly functionalized phosphonylated aziridine motif.
Topics: Aziridines; Diphosphonates; Organophosphonates
PubMed: 33476157
DOI: 10.1021/acs.joc.0c02434 -
Chemical Research in Toxicology 1992A reaction pathway by which thiotepa (N,N',N''-triethylenethiophosphoramide) and tepa (N,N',N''-triethylenethiophosphoramide), its major metabolite in humans, alkylate...
A reaction pathway by which thiotepa (N,N',N''-triethylenethiophosphoramide) and tepa (N,N',N''-triethylenethiophosphoramide), its major metabolite in humans, alkylate and depurinate DNA involves hydrolysis to aziridine (ethylene imine), a highly reactive monofunctional alkylating agent. Hydrolytic cleavage of an N-P bond of thiotepa releases aziridine which reacts with DNA, resulting in depurination and formation of the stable N-7 adduct 7-(2-aminoethyl)guanine and an aminoethyl adduct of adenine. Chromatographically identical alkylated products were observed in the reaction of thiotepa and tepa with individual nucleosides. Adducts with deoxycytidine or thymidine were not detected. Aziridine was measured by HPLC after derivatization with 1,2-naphthoquinone 4-sulfate. On the basis of the identity of the DNA adducts and the rate of formation of aziridine by hydrolysis in vitro, thiotepa is concluded to be a lipophilic, stabilized form of aziridine which serves as a cell-penetrating carrier of aziridine.
Topics: Alkylating Agents; Aziridines; Chromatography, High Pressure Liquid; DNA; Hydrogen-Ion Concentration; Hydrolysis; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Nucleosides; Spectrophotometry, Ultraviolet; Thiotepa; Triethylenephosphoramide
PubMed: 1374653
DOI: 10.1021/tx00025a016 -
Macromolecular Rapid Communications Sep 2022Providing access to diverse polymer structures is highly desirable, which helps to explore new polymer materials. Poly(thioester sulfonamide)s, combining both the...
Providing access to diverse polymer structures is highly desirable, which helps to explore new polymer materials. Poly(thioester sulfonamide)s, combining both the advantages of thioesters and amides, however, are rarely available in polymer chemistry. Here, the ring-opening copolymerization (ROCOP) of cyclic thioanhydride with N-sulfonyl aziridine using mild phosphazene base, resulting in well-defined poly(thioester sulfonamide)s with highly alternative structures, high yields, and controlled molecular weights, is reported. Additionally, benefiting from the mild catalytic process, this ROCOP can be combined with ROCOP of N-sulfonyl aziridines with cyclic anhydrides to produce novel block copolymers.
Topics: Aziridines; Polymerization; Polymers; Sulfonamides
PubMed: 35578395
DOI: 10.1002/marc.202200140