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International Journal of Molecular... Dec 2021-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective...
-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective to amide carbonyl at a low (-78 °C) temperature. These ketones, in reaction with organolithium reagents, give symmetrical and unsymmetrical aziridinyl carbinols. The usage of excess phenyllithium may serve as a special N-Boc-protecting group cleavage method for acid-sensitive substrates.
Topics: Aziridines; Ketones; Lithium; Methanol; Molecular Structure; Organometallic Compounds; Stereoisomerism
PubMed: 34884949
DOI: 10.3390/ijms222313145 -
Organic Letters Jan 2022We disclose a silver-catalyzed trifluoromethoxylation of -tosyl aziridines with trifluoromethyl arylsulfonate. The protocol is characterized by its mild conditions,...
We disclose a silver-catalyzed trifluoromethoxylation of -tosyl aziridines with trifluoromethyl arylsulfonate. The protocol is characterized by its mild conditions, simple operations, and good chemo- and regioselectivity. In addition, the trifluoromethoxylation of trisubstituted aziridines could construct C-OCF quaternary centers exclusively, which is quite rare. This method unlocks a new catalytic blueprint for accessing β-trifluoromethoxylated amines, which could be important building blocks in synthetic chemistry.
PubMed: 35023747
DOI: 10.1021/acs.orglett.1c04226 -
Nature Communications Jun 2022The activation of aziridines typically involves the use of strong Lewis acids or transition metals, and methods relying on weak interactions are rare. Herein, we report...
The activation of aziridines typically involves the use of strong Lewis acids or transition metals, and methods relying on weak interactions are rare. Herein, we report that cooperative chalcogen bonding interactions in confined sites can activate sulfonyl-protected aziridines. Among the several possible distinct bonding modes, our experiments and computational studies suggest that an activation mode involving the cooperative Se···O and Se···N interactions is in operation. The catalytic reactions between weakly bonded supramolecular species and nonactivated alkenes are considered as unfavorable approaches. However, here we show that the activation of aziridines by cooperative Se···O and Se···N interactions enables the cycloaddition of weakly bonded aziridine-selenide complex with nonactivated alkenes in a catalytic manner. Thus, weak interactions can indeed enable these transformations and are an alternative to methods relying on strong Lewis acids.
Topics: Alkenes; Aziridines; Chalcogens; Cycloaddition Reaction; Lewis Acids
PubMed: 35732663
DOI: 10.1038/s41467-022-31293-5 -
Bone Marrow Transplantation Jan 2023For acute lymphoblastic leukemia (ALL) patients, total body irradiation (TBI)- based conditioning regimens are the first choice specially in young population. However,...
Thiotepa, busulfan and fludarabine conditioning-regimen is a promising approach for older adult patients with acute lymphoblastic leukemia treated with allogeneic stem cell transplantation.
For acute lymphoblastic leukemia (ALL) patients, total body irradiation (TBI)- based conditioning regimens are the first choice specially in young population. However, several studies have shown an equivalence in clinical outcomes with thiotepa-based conditioning regimen. We performed a retrospective study to evaluate the outcome of adult ALL patients who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with a thiotepa-busulfan-fludarabine (TBF) myeloablative conditioning regimen with reduced toxicity. Fifty-five patients received a TBF regimen. The median age of the patients was 51 years (range, 17 to 72.4). Most patients had a diagnosis of B-ALL (93%) with 7% having T-ALL. Two - and 5-year overall survival was 73.2% and 64%, respectively. At 2 years, leukemia-free survival and GVHD-free, relapse-free survival were 59.5% and 57.6%, and at 5 years, 53.4% and 51.8%, respectively. The 5-year non-relapse mortality was 15%. The day 180 cumulative incidence (CI) of grade II-IV acute GVHD and grade III-IV acute GVHD were 38.2% and 5.5%, respectively. At 2 years, the CI of chronic GVHD and extensive chronic GVHD was 16.9% and 1.9%, respectively. Our study results do suggest that using TBF as the conditioning regimen in adult ALL patients is a promising option with acceptable toxicity.
Topics: Humans; Aged; Adolescent; Young Adult; Adult; Middle Aged; Busulfan; Thiotepa; Retrospective Studies; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Vidarabine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Graft vs Host Disease; Transplantation Conditioning
PubMed: 36224494
DOI: 10.1038/s41409-022-01841-0 -
Polymers Aug 2022-Sulfonyl-activated aziridines are known to undergo anionic-ring-opening polymerizations (AROP) to form polysulfonyllaziridines. However, the post-polymerization...
-Sulfonyl-activated aziridines are known to undergo anionic-ring-opening polymerizations (AROP) to form polysulfonyllaziridines. However, the post-polymerization deprotection of the sulfonyl groups from polysulfonyllaziridines remains challenging. In this report, the polymerization of -butyl aziridine-1-carboxylate () is reported. has an electron-withdrawing tert-butyloxycarbonyl (BOC) group on the aziridine nitrogen. The BOC group activates the aziridine for AROP and allows the synthesis of low-molecular-weight poly() chains. A C NMR spectroscopic analysis of poly() suggested that the polymer is linear. The attainable molecular weight of poly() is limited by the poor solubility of poly() in AROP-compatible solvents. The deprotection of poly() using trifluoroacetic acid (TFA) cleanly produces linear polyethyleneimine. Overall, these results suggest that carbonyl groups, such as BOC, can play a larger role in the in the activation of aziridines in anionic polymerization and in the synthesis of polyimines.
PubMed: 36015510
DOI: 10.3390/polym14163253 -
Organic & Biomolecular Chemistry Feb 2022N-Heterocycles can be found in natural products and drug molecules and are indispensable components in the area of organic synthesis, medicinal chemistry and materials... (Review)
Review
N-Heterocycles can be found in natural products and drug molecules and are indispensable components in the area of organic synthesis, medicinal chemistry and materials science. The construction of these N-containing heterocycles by traditional methods usually requires the preparation of reactive intermediates. In the past decades, with the rapid growth of transition metal catalysed coupling reactions, syntheses of heterocycles from precursors with inert chemical bonds have become a challenge. More recently, in the field of transition metal associated C-H direct functionalization, efficient methods have been developed for the syntheses of N-heterocyclic compounds such as aziridines, azetidines, indoles and quinolines under the click type of reaction mode. In this review, representative synthetic methodologies developed in the recent 10 years for the preparation of this small class of N-heterocycles the Pd-catalysed C-H activation and C-N bond formation pathway are discussed. We hope this article will provide new insights from the strategies highlighted into future molecular design, synthesis and applications in medical and materials sciences.
PubMed: 35044404
DOI: 10.1039/d1ob02146j -
Journal of the American Chemical Society Nov 2022Non-heme iron enzymes are versatile catalysts in the biosynthesis of medicinal natural products and have attracted increasing attention as practical catalytic tools in...
Non-heme iron enzymes are versatile catalysts in the biosynthesis of medicinal natural products and have attracted increasing attention as practical catalytic tools in chemical synthesis due to their ability to perform chemically challenging transformations. The Fe(II)/α-ketoglutarate-dependent oxygenase TqaL catalyzes unusual aziridine formation from l-Val via cleavage of the unactivated C-H bond. However, the mechanistic details as well as the synthetic potential of TqaL-catalyzed ring closure remain unclear. Herein, we show that the TqaL-catalyzed aziridination of l-Val proceeds with an atypical, mixed stereochemical course involving both the retention and inversion of the C3(C) stereocenter. It is also demonstrated that TqaL accepts l-Ile and l--Ile to generate the same diastereomeric pairs of aziridine products via an enzyme-controlled, stereoconvergent process. Our mutagenesis studies reveal that the reaction type (aziridination versus hydroxylation) and the stereochemical outcome are regulated by Ile343 and Phe345. Proper substitutions of Ile343 or Phe345 also make TqaL highly active toward the oxidation of α-amino acid substrates. This work provides mechanistic insights into the stereoselectivity and substrate specificity of the TqaL reactions.
Topics: Ketoglutaric Acids; Oxygenases; Substrate Specificity; Aziridines; Ferrous Compounds
PubMed: 36395461
DOI: 10.1021/jacs.2c08116 -
Acta Chimica Slovenica Jun 2022Optimized conditions for the synthesis of fully deprotected (2R)-aziridine containing dipeptides are described. Preparation of fully protected N- and C- terminal...
Optimized conditions for the synthesis of fully deprotected (2R)-aziridine containing dipeptides are described. Preparation of fully protected N- and C- terminal aziridine containing dipeptides was found to be straightforward and high yielding for the majority of compounds, whereas their full deprotection was possible only for C-terminal analogs. Deprotection of N-terminal derivatives using standard procedures of peptide chemistry was found difficult providing only mixtures of unidentifiable products. The described molecules have potential as building blocks in synthetic chemistry, in the chemical biology arena, as covalent modifiers, and as biomarkers.
Topics: Aziridines; Dipeptides
PubMed: 35861086
DOI: 10.17344/acsi.2021.6673 -
Beilstein Journal of Organic Chemistry 2022Cyclooctene endoperoxide was used as the key compound for the synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol. Reduction of the cyclooctene...
Cyclooctene endoperoxide was used as the key compound for the synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol. Reduction of the cyclooctene endoperoxide, prepared by photooxygenation of -1,3-cyclooctadiene, with zinc gave a cyclooctenediol and then benzylation of the hydroxy group yielded dibenzylated cyclooctene. Oxidation of the latter compound by OsO/NMO followed by mesylation of the hydroxy group provided bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate. Reaction of the bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate with NaN gave 2-azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate. Reduction of the azide group and debenzylation to give an amine provided the new 3-aminocyclooctanetriol. Treatment of the 2-azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate with Zn/NHCl and debenzylation resulted in the target aziridinecyclooctanediol.
PubMed: 36447522
DOI: 10.3762/bjoc.18.163 -
Biomedicines Dec 2021We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified...
We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore the possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (comet assay). Cells deficient in the nucleotide excision repair (NER) pathway were hypersensitive to the cytotoxicity of this compound. These results suggest that AzGalp induces bulky DNA adducts, and that cancer cells lacking a functional NER pathway may be particularly vulnerable to the anticancer effects of this aziridine. Several experiments revealed that neither the generation of oxidative stress nor the inhibition of glycolysis played a significant role in the cytotoxicity of AzGalp. Combinations of AzGalp with oxaliplatin or 5-fluorouracil slightly improved the ability of both anticancer drugs to selectively kill cancer cells. AzGalp also showed selective cytotoxicity against a panel of malignant cells versus normal cells; the highest selectivity was observed for two acute promyelocytic leukemia cell lines. Additional preclinical studies are necessary to evaluate the anticancer potential of AzGalp.
PubMed: 35052721
DOI: 10.3390/biomedicines10010041