-
Blood Nov 2023Secondary central nervous system (CNS) lymphoma (SCNSL) is a rare but clinically challenging scenario with historically disappointing outcomes. SCNSL refers to lymphoma...
Secondary central nervous system (CNS) lymphoma (SCNSL) is a rare but clinically challenging scenario with historically disappointing outcomes. SCNSL refers to lymphoma that has spread into the CNS concurrently with systemic disease or CNS relapse during or after frontline immunochemotherapy, presenting with or without systemic lymphoma. Diffuse large B-cell lymphoma (DLBCL) denotes the most common entity, but an increased incidence is observed in other histologies, such as Burkitt lymphoma and mantle-cell lymphoma. The incidence, timing in disease course, location, evidence supporting the use of CNS prophylaxis, and treatment pathways vary according to histology. No randomized data exist to delineate the best treatment approaches with current recommendations based on retrospective and single-arm studies. However, a regimen comprising immunochemotherapy, incorporating agents that cross the blood-brain barrier, followed by thiotepa-containing conditioning and autologous stem-cell transplant outlined in the international MARIETTA study demonstrated improvement in outcomes, representing a major accomplishment in the care of patients with DLBCL with SCNSL. Anti-CD19 chimeric antigen receptor T cell denotes a paradigm shift in the treatment of patients with systemic aggressive lymphomas, with emerging data also demonstrating efficacy without higher neurotoxicity in those with SCNSL. In this manuscript we discuss 5 clinical scenarios and review the evidence supporting our recommendations.
Topics: Humans; Adult; Retrospective Studies; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Central Nervous System Neoplasms; Thiotepa; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37702537
DOI: 10.1182/blood.2023020168 -
Molecules (Basel, Switzerland) Apr 2024The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and...
The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π-stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands.
PubMed: 38731454
DOI: 10.3390/molecules29091963 -
Chembiochem : a European Journal of... Jun 2024Only 0.016% of all known natural products contain an aziridine ring, but this unique structural feature imparts high reactivity and cytotoxicity to the compounds in...
Only 0.016% of all known natural products contain an aziridine ring, but this unique structural feature imparts high reactivity and cytotoxicity to the compounds in which it is found. Until 2021, no naturally occurring azirdine-forming enzymes had been identified. Since 2021, the biosynthetic enzymes for ~10% of known aziridine containing natural products have been identified and characterized. This article describes the recent advances in our understanding of enzyme-catalyzed aziridine formation in the context of historical means of azirdine formation through synthetic chemistry.
PubMed: 38830838
DOI: 10.1002/cbic.202400295 -
Chem Jul 2023In this review, selected recent advances in the preparation and reactivity of aziridines using modern synthetic approaches are highlighted, while comparing these new...
In this review, selected recent advances in the preparation and reactivity of aziridines using modern synthetic approaches are highlighted, while comparing these new strategies with more classical approaches. This critical analysis is designed to help identify current gaps in the field and is showcasing new and exciting opportunities to move the chemistry of aziridines forward in the future.
PubMed: 37681216
DOI: 10.1016/j.chempr.2023.04.010 -
Synthesis Sep 2023This short review summarizes our laboratory's development of benzylboronic esters as nucleophiles. Activation of the benzylboronic ester is achieved by irreversible...
This short review summarizes our laboratory's development of benzylboronic esters as nucleophiles. Activation of the benzylboronic ester is achieved by irreversible coordination of an alkyllithium Lewis base to form a nucleophilic benzylboronate. This boronate was found to react with aldehydes, imines, ketones and alkyl bromides. A copper catalyst was employed in reactions of the boronate with epoxides and aziridines.
PubMed: 37790600
DOI: 10.1055/a-2072-2754 -
Chemical Record (New York, N.Y.) Sep 2023The fluorinated building block strategy and the direct fluorination strategy are of great importance for the synthesis of new fluorinated molecules. These strategies... (Review)
Review
The fluorinated building block strategy and the direct fluorination strategy are of great importance for the synthesis of new fluorinated molecules. These strategies complement each other and can be combined to develop a new methodology for the construction of a wide variety of fascinating organofluorine compounds. In our opinion, the versatile building blocks used in this method should satisfy the following conditions: 1) readily prepared from commercially available reagents; 2) easy to handle; 3) storage under ordinary conditions without noticeable decomposition; 4) wide applicability. Based on the aforementioned requirements, we focused on the use of vinyl sulfonium salts. This brief review describes the synthesis of five types of fluorinated vinyl sulfonium salts and their reactions. Especially, we featured typical fluorinated groups containing trifluoromethyl (CF ), difluoromethyl (CF H), monofluoromethyl (CFH ), monofluoro (F) or β-bromotetrafluoroethyl (BrCF CF ) moieties in combination with vinyl sulfonium salts.
PubMed: 36744592
DOI: 10.1002/tcr.202200270 -
JACS Au Oct 2023Tropane alkaloids are an important class of biologically active small molecules characterized by their 8-azabicyclo[3.2.1]octane core. Because of their numerous...
Tropane alkaloids are an important class of biologically active small molecules characterized by their 8-azabicyclo[3.2.1]octane core. Because of their numerous medicinal applications, microbial biosynthesis and a variety of chemical syntheses have been designed for individual family members. However, current approaches are not amenable to late-stage structural diversification at N8, C3, C6, or C7, positions that are critical for modulating the biological properties of these molecules. Here, we describe a general approach to the synthesis of tropane alkaloids and their analogues that relies on the construction of the 8-azabicyclo[3.2.1]octane core through aziridination of a cycloheptadiene intermediate, followed by vinyl aziridine rearrangement. Using this strategy, we synthesized six tropane alkaloids and several analogues in only 5-7 steps. Given that the tropane alkaloid scopolamine has been reported to promote structural neuroplasticity and produce antidepressant effects, we tested five tropane-containing compounds for their ability to promote dendritic spine growth in cultured cortical neurons. We found that the orientation of the C3 substituent may play a role in the psychoplastogenic effects of tropane alkaloids. Our work provides a robust platform for producing tropane analogs for future structure-activity relationship studies.
PubMed: 37885569
DOI: 10.1021/jacsau.3c00472 -
National Science Review Oct 2023Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the...
Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery.
PubMed: 38059062
DOI: 10.1093/nsr/nwad187 -
Organic & Biomolecular Chemistry Nov 2023The remarkable biological activities of γ-lactams have stimulated the search for efficient synthetic methods to achieve these scaffolds. In this work, we have developed...
The remarkable biological activities of γ-lactams have stimulated the search for efficient synthetic methods to achieve these scaffolds. In this work, we have developed a simple one-pot diastereoselective synthesis of new γ-lactams from ketoaziridines with moderate to good yields the Horner-Wadsworth-Emmons reaction, followed by an intramolecular ester-aziridine cyclization and its opening . Preliminary efforts towards an enantioselective version of this method are also reported.
PubMed: 37966723
DOI: 10.1039/d3ob01568h -
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