A Stereoselective Entry to Enantiopure (S)-2-Amino-2-methyl-5-arylpent-4-ynoic Acids and Evaluation of Their Inhibitory Activity against Bacterial Collagenase G DOI Open Access

Hegine I. Hakobyan,

Silva M. Jamgaryan,

A. S. Sargsyan

et al.

Symmetry, Journal Year: 2023, Volume and Issue: 15(10), P. 1924 - 1924

Published: Oct. 16, 2023

Nowadays, amino acids (AAs) and peptides with bulky side chains hold significant interest for organic synthesis the modern pharma industry. Non-proteinogenic (or unnatural) AAs are key building blocks used obtaining pharmaceutically relevant development of chiral molecular catalysts, they extensively in total complex natural compounds. Thus, an elaboration cost-effective methods preparation novel unnatural to increase their structural diversity is highly desirable. In this context, herein, we present asymmetric metal-templated a number enantiomerically pure (S)-2-amino-2-methyl-5-arylpent-4-ynoic starting from commercially available reagents Belokon’s auxiliary (S)-BPB, namely (S)-2-(N-benzylprolyl)aminobenzophenone. The construction Ni(II) alanine (Ala) subsequent propargylation, arylation by Sonogashira cross-coupling reaction using various aryl halides, and, finally, acidic decomposition obtained complexes deliver target α,α-disubstituted featuring triple bond chain. Next, Fmoc-protected α-AAs dipeptide were synthesized. Finally, examined peptide as collagenase inhibitors.

Language: Английский

FDA approved fluorine-containing drugs in 2023 DOI
Qian Wang,

Yeping Bian,

Gagan Dhawan

et al.

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: 35(11), P. 109780 - 109780

Published: March 15, 2024

Language: Английский

Citations

18
Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters DOI Creative Commons

Youlong Du,

Haibo Mei, Ata Makarem

et al.

Beilstein Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 20, P. 212 - 219

Published: Feb. 2, 2024

An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper-catalyzed conditions has been developed, which affords various unsymmetrical N , -diacyl-β-amino esters in good to excellent yields. The features mild conditions, a wide scope β-amino acids, also applicability large-scale synthesis, thus providing way for the synthesis β-diacylamino esters. Furthermore, this represents first example Mumm rearrangement

Language: Английский

Citations

5
Recent Advances on the Synthesis and Application of Tetrahydro‐β‐Carbolines DOI

Youlong Du,

Anas Semghouli,

Haibo Mei

et al.

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(14), P. 3050 - 3084

Published: May 22, 2024

Abstract Tetrahydro‐ β ‐carbolines (TH Cs) also known as tryptolines serve important structural elements in natural products and pharmaceutical compounds, they are utilized drug discovery. They display diverse bioactivities, including anticancer, antifungal, antiparasitic, anti‐ischemic, anti‐inflammatory, other activities. Besides their pharmacological biological significance, these motifs extensively used the production of bioactive compounds. This review is intended to summarize recent advancements chemistry this compound class, synthesis applications organic synthetic intermediates molecules.

Language: Английский

Citations

5
Trifluoromethylthiolation of Tryptophan and Tyrosine Derivatives: A Tool for Enhancing the Local Hydrophobicity of Peptides DOI Creative Commons
Jure Gregorc, Nathalie Lensen, Grégory Chaume

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(18), P. 13169 - 13177

Published: Sept. 6, 2023

The incorporation of fluorinated groups into peptides significantly affects their biophysical properties. We report herein the synthesis Fmoc-protected trifluoromethylthiolated tyrosine (CF3S-Tyr) and tryptophan (CF3S-Trp) analogues on a gram scale (77–93% yield) demonstrate use as highly hydrophobic building blocks for peptide chemistry. developed methodology was successfully applied to late-stage regioselective trifluoromethylthiolation Trp residues in short (66–80% various CF3S-analogues biologically active monoamines. To prove concept, Fmoc-(CF3S)Tyr -Trp were incorporated endomorphin-1 chain (EM-1) model tripeptides by solid-phase synthesis. A remarkable enhancement local hydrophobicity quantified chromatographic index determination method, demonstrating high potential CF3S-containing amino acids rational design bioactive peptides.

Language: Английский

Citations

11
Enantioselective Carbon Isotope Exchange DOI
Michael G. J. Doyle, Odey Bsharat, Anna Sib

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 18804 - 18810

Published: July 5, 2024

The synthesis of isotopically labeled organic molecules is vital for drug and agrochemical discovery development. Carbon isotope exchange emerging as a leading method to generate carbon-labeled targets, which are sought over hydrogen-based labels due their enhanced stability in biological systems. While many bioactive small bear carbon-containing stereocenters, direct enantioselective carbon reactions have not been established. We describe the first example an reaction, where (radio)labeled α-amino acids can be generated from unlabeled precursors using stoichiometric chiral aldehyde receptor with CO

Language: Английский

Citations

4
Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex DOI Creative Commons

Maurizio Iannuzzi,

Thomas Hohmann, Michael Dyrks

et al.

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 659 - 669

Published: March 21, 2025

Fluorinated amino acids are essential building blocks in the spheres of protein engineering and medicinal chemistry. In last decades, a large number different synthetic strategies have been developed to produce variety fluorinated acids. Still, obtaining great quantities can be challenging, or corresponding pathways heavily time-consuming synthetically challenging. this context, chiral Ni(II) complexes powerful tools obtain tailor‑made non‑canonical work, we wanted take advantage strategy extend range method include additional We synthesized two analogs phenylalanine, which still unexplored context peptide Furthermore, both diastereomers trifluoroleucine were synthesized, demonstrating that described also applied synthesize enantio‑ diastereomerically pure γ‑branched This work further underlines importance synthesis

Language: Английский

Citations

0
Design and synthesis of fluorine aromatic scaffolds containing drugs approved by the US FDA from 2002 to 2022 DOI Creative Commons
Pengfei Xu,

Lijun Zhu,

Desheng Zhang

et al.

Results in Chemistry, Journal Year: 2024, Volume and Issue: 7, P. 101446 - 101446

Published: Jan. 1, 2024

There are totally 93 fluorine aromatic scaffolds containing drugs approved by U.S. Food and Drug Administration from 2002 to 2022. The proportion of fluorinated skeleton in is increasing recent ten years, which indicates the unique important attributes atom. introduction fragments into molecules can influence structure conformation, intrinsic potency selectivity pharmacokinetic properties productively. Additionally, 18F has been applied as a significant useful positron emission tomography isotope for vivo imaging technology. This review mainly concentrated on application synthesis methods US FDA We hoped that this deep insight perspective synthetic delivery these could offer practical creative inspirations development atom new drug discovery.

Language: Английский

Citations

3
Asymmetric Synthesis of Unprotected Tryptophan Derivatives Using Gramines via Ni(II) Complexes DOI
Zhekai Xiao, Yazhou Li, Yuzhu Wu

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

0
Sequential Michael addition, cross-coupling and [3 + 2] cycloaddition reactions within the coordination sphere of chiral Ni(ii) Schiff base complexes derived from dehydroamino acids: pathways to the asymmetric synthesis of structurally diverse O-substituted serine and threonine analogs DOI Creative Commons

E. A. Khachatryan,

Lusine Sahakyan, Anna S. Tovmasyan

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(14), P. 10558 - 10564

Published: Jan. 1, 2025

An approach to the synthesis of a series novel, enantiomerically pure analogs β-hydroxy-α-amino acids is reported.

Language: Английский

Citations

0
CHIRAL, FLUORINE-CONTAINING PHARMACEUTICALS DOI Open Access
Jianlin Han, Alicja Wzorek, Gagan Dhawan

et al.

Ukrainian Chemistry Journal, Journal Year: 2025, Volume and Issue: 91(2), P. 55 - 90

Published: March 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.

Language: Английский

Citations

0