Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

Molecules, Год журнала: 2021, Номер 26(9), С. 2757 - 2757

Опубликована: Май 7, 2021

The purpose of this review is to highlight the necessity conducting tests gauge magnitude self-disproportionation enantiomers (SDE) phenomenon ensure veracity reported enantiomeric excess (ee) values for scalemic samples obtained from enantioselective reactions, natural products isolation, etc. SDE always occurs some degree whenever any sample subjected physicochemical processes concomitant with fractionation sample, thus leading erroneous reporting true ee if due care not taken either preclude effects by measurement prior application processes, suppressing SDE, or evaluating all fractions sample. Or even avoiding altogether possible. There a clear conduct assess applied and updated improved recommendations described herein cover chromatography involving gas-phase transformations such as evaporation sublimation.

Язык: Английский

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Asymmetric Synthesis of Unprotected Tryptophan Derivatives Using Gramines via Ni(II) Complexes

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

We herein report the synthesis of substituted tryptophans using Ni(II) complexes glycine and gramines. This reaction proceeds under operationally convenient mild conditions, inexpensive, nontoxic, easily accessible reagents. The reactions feature high yields virtually complete thermodynamically controlled diastereoselectivity, providing a method for tailor-made tryptophans.

Язык: Английский

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CHIRAL, FLUORINE-CONTAINING PHARMACEUTICALS

Ukrainian Chemistry Journal, Год журнала: 2025, Номер 91(2), С. 55 - 90

Опубликована: Март 25, 2025

Fluorine is a key element in drug design due to its ability enhance metabolic stability, binding affinity, and bioavailability. Fluorine’s properties lead more stable drugs with longer half-lives, reducing dosing frequency improving patient compliance. Its small size high electronegativity also improve resulting effective treatments lower doses. For example, fluorine increases compound’s cross cell memb­ranes. This article highlights advancements chiral, fluorine-containing pharmaceuticals introduced over the past five years, focusing on their synthesis, therapeutic benefits, mechanisms of action, impact efficacy safety. Chiral molecules, essential development, exist two enantiomeric forms distinct biological activities. Synthesizing involves techniques like asymmetric synthesis produce pure enantiomers, increased potency, selectivity, reduced side effects. Understanding action provides valuable insights into Reviewing recently FDA-approved chiral offers chemistry development future innovations. Recent FDA approvals highlight significance various areas, enabling targeted treatments. Analyzing these reveals trends shaping development’s future. The addresses need for research self-disproportionation enantiomers (SDE) fluorinated compounds concerns about excessive levels. SDE can affect pharmaceutical product purity. Research ensures quality. Additionally, fluorine’s widespread use raises environmental health concerns, necessitating studies long-term effects mitigation strategies.

Язык: Английский

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Asymmetric Metal‐Templated Route to Amino Acids with 3‐Spiropyrrolidine Oxindole Core via a 1,3‐Dipolar Addition of Azomethine Ylides to a Chiral Dehydroalanine Ni(II) Complex

Advanced Synthesis & Catalysis, Год журнала: 2022, Номер 364(14), С. 2395 - 2402

Опубликована: Июнь 20, 2022

Abstract We herein developed a protocol for the asymmetric synthesis of artificial AAs featuring 3‐spiropyrrolidine oxindole skeletal with continuous tetrasubstituted carbon stereocenters by 1,3‐dipolar cycloaddition reaction in situ generated azomethine ylides chiral dehydroalanine Ni(II) complex. A three‐component complex various isatins and green solvent (ethanol) provided series diastereomeric complexes high dr (>20:1) 40–86% yields. The formation different regioisomers case sarcosine proline was explained using quantum chemical calculation. acidic decomposition obtained led to target unnatural core. auxiliary ligand recovered after reused starting complex‐substrate. magnified image

Язык: Английский

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Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N-Acetylamino Malonic Acid Derivatives

Organic Letters, Год журнала: 2023, Номер 25(44), С. 7958 - 7962

Опубликована: Сен. 27, 2023

Broad application of α,α-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing that relies on anodic decarboxylation-intramolecular etherification inexpensive readily available N-acetylamino malonic monoesters under Hofer-Moest reaction conditions. The decarboxylative cyclization proceeds constant current conditions undivided cell aqueous medium without any added base. A successful bioisosteric replacement the 1-aminocyclohexane-1-carboxylic subunit by scaffold cathepsin K inhibitor balicatib helped to reduce lipophilicity while retaining low nanomolar enzyme inhibitory potency comparable microsomal stability.

Язык: Английский

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Design, Synthesis, and Functional Studies on Noscapine and Cotarnine Amino Acid Derivatives as Antitumor Agents

ACS Omega, Год журнала: 2023, Номер 8(48), С. 45502 - 45509

Опубликована: Ноя. 23, 2023

Noscapine, a phthalide isoquinoline alkaloid isolated from the opium poppy, alongside cotarnine, tetrahydroisoquinoline (THIQ) scaffold produced by oxidative degradation of noscapine, has exhibited antitumor activities against several types cancer. Although derivatization with amino acids is regarded as promising strategy to improve chemotherapeutics' anticancer properties, acid conjugates noscapine and cotarnine have been least investigated. In present study, 20 conjugated derivatives at 6-position were synthesized evaluated for activity in both vitro vivo conditions. Analysis antiproliferative 4T1 mammary carcinoma tumor cells showed that compounds 6h (noscapine–phenylalanine), 6i (noscapine–tryptophan), 10i (cotarnine–tryptophan) IC50 values 11.2, 16.3, 54.5 μM, respectively, found be far more potent than (IC50 = 215.5 μM) 575.3 consequently opted further characterization. Annexin V propidium iodide staining followed flow cytometry demonstrated improved apoptotic 6h, 6i, compared those cotarnine. murine model carcinoma, noscapine–tryptophan inhibited growth effectively other without adverse effects. Moreover, molecular docking studies conducted on tubulin intracellular target suggested good correlation experimental observations. Based these results, could candidate preclinical investigations.

Язык: Английский

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Tailor‐Made Amino Acids in Pharmaceutical Industry: Synthetic Approaches to Aza‐Tryptophan Derivatives

Chemistry - A European Journal, Год журнала: 2021, Номер 27(70), С. 17510 - 17528

Опубликована: Окт. 25, 2021

Over the recent years there has been a noticeable upsurge of interest in aza-analogs tryptophan which are isosteric to latter and found numerous applications medicinal, bioorganic chemistry, peptide research. In present review article, five aza-tryptophan derivatives profiled, including aza-substitution positions 2, on five-membered ring, as well 4, 5, 6, 7 six-membered ring. A detailed comprehensive literature overview synthetic methods for preparation these aza-tryptophans is presented general facets biological properties most promising discussed.

Язык: Английский

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New drugs appearing on the market in 2023: molecules containing fluorine and fragments of tailor-made amino acids

Ukrainica Bioorganica Acta, Год журнала: 2024, Номер 19(1), С. 3 - 20

Опубликована: Июнь 30, 2024

This article profiles eight new FDA-approved drugs containing fluorine along with the fragments of amino acids or their derivatives. These pharmaceuticals include Eflornithine, Lotilaner, Leniolisib, Fezolinetant, Nirmatrelvir, Repotrectinib, Nirogacestat, and Pirtobrutinib, representing such therapeutic areas as cancer, neuromuscular disorder, immunodeficiency, virology, infectious diseases. Importance fluorination, acid residues well chirality in design is highlighted

Язык: Английский

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Design, synthesis, and biological evaluation of ocotillol derivatives fused with 2-aminothiazole via A-ring as modulators of P-glycoprotein-mediated multidrug resistance

European Journal of Medicinal Chemistry, Год журнала: 2022, Номер 243, С. 114784 - 114784

Опубликована: Сен. 21, 2022

Язык: Английский

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Dynamic Thermodynamic Resolution of Unprotected Amino Acids Using Ni(II) Chiral Schiff Bases

European Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Июль 16, 2024

Abstract Dynamic thermodynamic resolution of amino acids (AAs) using Ni(II) chiral Schiff bases is one the simplest and most efficient methods to obtain optically active AAs. A comparison reactivity 36 rac‐AAs with complex revealed that this method can be easily applied dynamic S/R interconversion AAs unprotected functional groups. It also really for side‐chain modification AA derivatives groups on complex. Furthermore, antimicrobial activities synthesized complexes were evaluated, [( S , )− 3 g ( h i ] showed remarkable antibacterial activity against Micrococcus luteus a Gram positive bacterium.

Язык: Английский

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