Towards Enantiomerically Pure Unnatural α-Amino Acids via Photoredox Catalytic 1,4-Additions to a Chiral Dehydroalanine DOI Creative Commons
Paula Oroz, Claudio D. Navo, Alberto Avenoza

et al.

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(21), P. 14308 - 14318

Published: Sept. 30, 2022

Chemo- and diastereoselective 1,4-conjugate additions of anionic radical C-nucleophiles to a chiral bicyclic dehydroalanine (Dha) are described. Of particular importance, carbon photolysis by catalytic photoredox process using simple method with metal-free photocatalyst provides exceptional yields selectivities at room temperature. Moreover, these offer an excellent starting point for synthesizing enantiomerically pure carbon-β-substituted unnatural α-amino acids (UAAs), which could have high potential applications in chemical biology.

Language: Английский

Strategies to overcome cancer multidrug resistance (MDR) through targeting P-glycoprotein (ABCB1): An updated review DOI
Jinyun Dong, Yuan Li, Can Hu

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 249, P. 108488 - 108488

Published: July 11, 2023

Language: Английский

Citations

73
The Latest FDA-Approved Pharmaceuticals Containing Fragments of Tailor-Made Amino Acids and Fluorine DOI Creative Commons
Qian Wang, Jianlin Han, Alexander E. Sorochinsky

et al.

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(8), P. 999 - 999

Published: Aug. 14, 2022

Nowadays, the selective introduction of fluorine into bioactive compounds is a mature strategy in design drugs allowing to increase efficiency, biological half-life and bio-absorption. On other hand, amino acids (AAs) represent one most ubiquitious classes naturally occurring organic compounds, which are found over 40% newly marked small-molecule pharmaceutical medical formulations. The primary goal this work underscore two major trends modern pharmaceuticals. first dealing with unique structural characteristics provided by structure featuring an abundance functionality presence stereogenic center, all bodes well for successful development targeted bioactivity. second related fine-tuning desired activity pharmacokinetics fluorine. Historically, both were developed separately as innovative prolific approaches drug design. However, recent decades, these clearly converging leading ever-increasing number approved pharmaceuticals containing features

Language: Английский

Citations

43
New Approved Drugs Appearing in the Pharmaceutical Market in 2022 Featuring Fragments of Tailor-Made Amino Acids and Fluorine DOI Creative Commons
Nana Wang, Haibo Mei, Gagan Dhawan

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(9), P. 3651 - 3651

Published: April 22, 2023

The strategic fluorination of oxidatively vulnerable sites in bioactive compounds is a relatively recent, widely used approach allowing us to modulate the stability, bio-absorption, and overall efficiency pharmaceutical drugs. On other hand, natural tailor-made amino acids are traditionally as basic scaffolds for development molecules. main goal this review article emphasize these general trends featured recently approved

Language: Английский

Citations

30
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

1
New pharmaceuticals approved by FDA in 2020: Small‐molecule drugs derived from amino acids and related compounds DOI
Aiyao Liu, Jianlin Han,

Arina Nakano

et al.

Chirality, Journal Year: 2021, Volume and Issue: 34(1), P. 86 - 103

Published: Oct. 29, 2021

Abstract Amino acids (AAs) play an important role in the modern health industry as key synthetic precursors for pharmaceuticals, biomaterials, biosensors, and drug delivery systems. Currently, over 30% of small‐molecule drugs contain residues tailor‐made AAs or derived from them amino‐alcohols di‐amines. In this review article, we profile 12 AA‐derived new pharmaceuticals approved by FDA 2020. These newly introduced include Tazverik (epithelioid sarcoma), Gemtesa (overactive bladder), Zeposia (multiple sclerosis), Byfavo (induction maintenance procedural sedation), Cu 64 dotatate, Gallium 68 PSMA‐11 (both PET imaging), Rimegepant (acute migraine), Zepzelca (lung cancer), Remdesivir (COVID‐19), Amisulpride (nausea vomiting), Setmelanotide (obesity), Lonafarnib (progeria syndrome). For each compound, describe spectrum biological activity, medicinal chemistry discovery, preparation.

Language: Английский

Citations

38
Highly Enantioselective Synthesis of N‐Unprotected Unnatural α‐Amino Acid Derivatives by Ruthenium‐Catalyzed Direct Asymmetric Reductive Amination DOI

Le’an Hu,

Yuan‐Zheng Wang,

Lei Xu

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(25)

Published: March 25, 2022

Abstract An unprecedented highly enantioselective Ru‐catalyzed direct asymmetric reductive amination of α‐keto amides with ammonium salts has been disclosed, efficiently offering valuable enantioenriched N‐unprotected unnatural α‐amino acid derivatives bearing a broad range aryl or alkyl α‐substituents. This protocol features easily accessible substrates, good functional‐group tolerance and excellent enantiocontrol, making it complementary approach to the known methods. Moreover, this method is also applicable preparation containing an additional stereogenic center at β‐position through dynamic kinetic resolution (DKR) process. Convenient transformations obtained products into chiral acids, drug intermediates, peptides, organocatalysts/ligands further showcase utility method.

Language: Английский

Citations

25
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
Asymmetric Michael Addition in Synthesis of β-Substituted GABA Derivatives DOI Creative Commons
Jianlin Han, Jorge Escorihuela, Santos Fustero

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(12), P. 3797 - 3797

Published: June 13, 2022

γ-Aminobutyric acid (GABA) represents one of the most prolific structural units widely used in design modern pharmaceuticals. For example, β-substituted GABA derivatives are found numerous neurological drugs, such as baclofen, phenibut, tolibut, pregabalin, phenylpiracetam, brivaracetam, and rolipram, to mention just a few. In this review, we critically discuss literature data reported on preparation substituted using Michael addition reaction key synthetic transformation. Special attention is paid asymmetric methods featuring synthetically useful stereochemical outcomes operational simplicity.

Language: Английский

Citations

21
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
Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions DOI Creative Commons
Jianlin Han, Alicja Wzorek, Karel D. Klika

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(9), P. 2757 - 2757

Published: May 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.

Language: Английский

Citations

26