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Organic & Biomolecular Chemistry Mar 2024Diamines play important roles in synthetic organic chemistry and thus facilitate life and materials sciences. Herein we report a cobalt-catalyzed ring opening,...
Diamines play important roles in synthetic organic chemistry and thus facilitate life and materials sciences. Herein we report a cobalt-catalyzed ring opening, nucleophilic amination of aziridines and azetidines with -fluorosulfonamides toward a wide range of 1,2- and 1,3-diamine derivatives in moderate to good yields under mild conditions.
PubMed: 38446010
DOI: 10.1039/d4ob00168k -
Chemical Communications (Cambridge,... Mar 2024The coupling of diaziridines with donor-acceptor aziridines (DAAs) has been achieved using Zn-catalysis to furnish imidazopyrazole-4,4-dicarboxylates [1,4]-hydride...
The coupling of diaziridines with donor-acceptor aziridines (DAAs) has been achieved using Zn-catalysis to furnish imidazopyrazole-4,4-dicarboxylates [1,4]-hydride shift. The use of Zn-catalysis, [1,4]-hydride shift, natural product modification and a late-stage molecular docking study are important practical features.
PubMed: 38445334
DOI: 10.1039/d4cc00226a -
Journal of the American Chemical Society Mar 2024The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the...
The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate β-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.
Topics: Amino Acids; Anti-Infective Agents
PubMed: 38427590
DOI: 10.1021/jacs.3c11560 -
Journal of Clinical and Experimental... Mar 2024Primary testicular lymphoma (PTL) frequently relapses in the central nervous system (CNS) despite prophylactic intrathecal chemotherapy, and the outcome for CNS...
Successful treatment of isolated central nervous system recurrence of primary testicular lymphoma by autologous stem cell transplantation using a conditioning regimen of thiotepa and busulfan.
Primary testicular lymphoma (PTL) frequently relapses in the central nervous system (CNS) despite prophylactic intrathecal chemotherapy, and the outcome for CNS recurrence of PTL is very poor. We report a case of isolated CNS recurrence of bilateral PTL. Our patient achieved complete response (CR) after rituximab-combination chemotherapy for PTL. Approximately five years later, isolated CNS recurrence of PTL occurred. Our patient achieved CR again after high-dose methotrexate therapy and autologous stem cell transplantation (ASCT) with a conditioning regimen of thiotepa and busulfan as a consolidation therapy. The secondary failure of platelet recovery, probably caused by busulfan, occurred after the platelet engraftment. Our patient has remained in CR for over three years. The treatment strategy for CNS recurrence of PTL is mainly whole-brain radiotherapy or high-dose methotrexate-based chemotherapy; however, CNS recurrence of PTL may occur again even after achieving CR. ASCT with a conditioning regimen of thiotepa and busulfan is the optimal consolidation therapy for secondary CNS lymphoma. To the best of our knowledge, this is the second reported case of a patient with isolated CNS recurrence of PTL successfully treated by ASCT with a conditioning regimen of thiotepa and busulfan as a consolidation therapy.
Topics: Humans; Thiotepa; Hematopoietic Stem Cell Transplantation; Busulfan; Methotrexate; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Lymphoma; Central Nervous System; Combined Modality Therapy; Stem Cell Transplantation; Transplantation Conditioning
PubMed: 38417873
DOI: 10.3960/jslrt.23039 -
American Journal of Reproductive... Mar 2024To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent...
PROBLEM
To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM).
METHODS
Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10 weeks of gestation), late miscarriage (between 10 and 24 weeks), ongoing pregnancy (beyond 10 weeks), and live birth (after 24 weeks) characterized by pregnancy with fetal heartbeat.
RESULTS
For each unit increase in aAnxA5 MOM, the odds of live birth after 24 weeks and ongoing pregnancy were reduced by 40.2% (OR = .598; 95%CI 0.406-0.882, P = .010) and 38.1% (OR = .619; 95%CI 0.424-0.904, P = .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR = 1.616; 95%CI 1.106-2.361, P = .013) and miscarriage (early + late miscarriage) (OR = 1.671; 95%CI 1.134-2.464, P = .010). Further subgroup analyses showed a decreased risk of live birth rates after 24 weeks of gestation in the two subgroups: maternal age ≥35 years (OR = .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR = .381; 95%CI 0.173-0.837).
CONCLUSIONS
Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24 weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3.
Topics: Pregnancy; Female; Humans; Retrospective Studies; Live Birth; Annexin A5; Abortion, Habitual; China; Aziridines; Benzoquinones
PubMed: 38407361
DOI: 10.1111/aji.13822 -
Polymers Feb 2024Commercially available poly(lactic acid) exhibits poor hydrolytic stability, which makes it impossible for use in durable applications. Therefore, a novel hydrolysis...
Commercially available poly(lactic acid) exhibits poor hydrolytic stability, which makes it impossible for use in durable applications. Therefore, a novel hydrolysis inhibitor based on an aziridine derivative as well as a novel stabilizer composition, containing an aziridine derivative and an acid scavenger, were investigated to improve the hydrolytic stability. To evaluate the stabilizing effect, the melt volume rate (MVR) and molecular weight were monitored during an accelerated hydrolytic aging in water at elevated temperatures. Temperatures were selected according to the glass transition temperature (~60 °C) of PLA. It was shown that the novel hydrolysis inhibitor as well as the novel stabilizer composition exhibited excellent performance during hydrolytic aging, exceeding commercially available alternatives, e.g., polymeric carbodiimides. A molecular weight analysis resulted in a molecular weight decrease of only 10% during approximately 850 h and up to 20% after 1200 h of hydrolytic aging, whereas poly(lactic acid) stabilized with a commercial polycarbodiimide revealed comparable molecular weight reductions after only 300 h. Furthermore, the stabilization mechanism of the aziridine derivative alone, as well as in the synergistic combination with the acid scavenger (calcium hydrotalcite), was investigated using nuclear magnetic resonance (NMR) spectroscopy. In addition to an improved hydrolytic stability, the thermal properties were also enhanced compared to polymeric carbodiimides.
PubMed: 38399884
DOI: 10.3390/polym16040506 -
The Journal of Organic Chemistry Mar 2024Aziridines are important structural motifs and intermediates, and several synthetic strategies for the direct aziridination of alkenes have been introduced. However,...
Aziridines are important structural motifs and intermediates, and several synthetic strategies for the direct aziridination of alkenes have been introduced. However, many of these strategies require an excess of activated alkene, suffer from competing side-reactions, have limited functional group tolerance, or involve precious transition metal-based catalysts. Herein, we demonstrate the direct aziridination of alkenes by combining sulfonyl azides as a triplet nitrene source with a catalytic amount of an organic dye functioning as photosensitizer. We show how the nature of the sulfonyl azide, in combination with the triplet-excited state energy of the photosensitizer, affects the aziridination yield and provide a mechanistic rationale to account for the observed dependence of the reaction yield on the nature of the organic dye and sulfonyl azide reagents. The optimized reaction conditions enable the aziridination of structurally diverse and complex alkenes, carrying various functional groups, with the alkene as the limiting reagent.
PubMed: 38358354
DOI: 10.1021/acs.joc.3c02709 -
Journal of the American Chemical Society Feb 2024The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and...
The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed through a regioselective aziridine ring opening.
PubMed: 38346145
DOI: 10.1021/jacs.3c13590 -
The Journal of Organic Chemistry Mar 2024Sp-enriched small molecules play a critical role in developing drug candidates. While designing analogues with greater sp character, a methodology utilizing a less...
Sp-enriched small molecules play a critical role in developing drug candidates. While designing analogues with greater sp character, a methodology utilizing a less explored cyclic-aziridine amide ring-opening reaction to generate sp-enriched scaffolds has been developed and reported. This methodology enables rapid access to substructures with higher fsp values, attracting greater attention within the past few decades. The reaction exhibits a wide reaction scope, featuring a highly sterically hindered phenolic ether, thiophenolic ethers, protected aniline formations, and aliphatic/heteroaromatic ring-containing aziridine amides as substrates. Additionally, this reaction provides access to congested tertiary ether formations through regioselective transformation, applicable to an extensive range of drug discovery targets, construction of complex small molecules, and natural product syntheses. The scaffolds developed show improved physicochemical properties.
PubMed: 38340064
DOI: 10.1021/acs.joc.3c02952 -
The Journal of Organic Chemistry Feb 2024A simple and atom economic protocol for the construction of C-X/C-C bonds via catalytic aminium radical-cation salt (Magic Blue)-initiated S2-type nucleophilic...
A simple and atom economic protocol for the construction of C-X/C-C bonds via catalytic aminium radical-cation salt (Magic Blue)-initiated S2-type nucleophilic ring-opening transformations of racemic and nonracemic aziridines with different hetero and carbon nucleophiles to afford various amino ethers, thioethers, and amines in up to 99% yield, and with perfect enantiospecificity for some substrates but reduced ee with others (for nonracemic aziridines), is developed. This aminium radical-cation salt-initiated, S2-type nucleophilic ring-opening strategy, along with various cyclization protocols, is employed to synthesize various biologically significant compounds.
PubMed: 38323416
DOI: 10.1021/acs.joc.3c02194