Exploring Simple Drug Scaffolds from the Generated Database Chemical Space Reveals a Chiral Bicyclic Azepane with Potent Neuropharmacology DOI
Aline Lucie Carrel, Adonis Yiannakas,

Jaap-Jan Roukens

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Zinc‐Catalyzed Enantioselective Formal (3+2) Cycloadditions of Bicyclobutanes with Imines: Catalytic Asymmetric Synthesis of Azabicyclo[2.1.1]hexanes DOI Open Access
Feng Wu, Wen‐Biao Wu, Yuanjiu Xiao

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(48)

Published: Sept. 2, 2024

Abstract The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp 3 )‐rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is scarcity of catalytic asymmetric cycloadditions BCBs to fulfill the need enantioenriched saturated bicycles in drug design development. In this study, an synthesis valuable azabicyclo[2.1.1]hexanes (aza‐BCHs) by enantioselective zinc‐catalyzed (3+2) with imines reported. proceeds effectively novel type BCB that incorporates 2‐acyl imidazole group diverse array alkynyl‐ aryl‐substituted imines. target aza‐BCHs, consist α‐chiral amine fragments two quaternary carbon centers, are efficiently synthesized up 94 % 96.5:3.5 er under mild conditions. Experimental computational studies reveal follows concerted nucleophilic ring‐opening mechanism This distinct from previous on Lewis acid‐catalyzed BCBs.

Language: Английский

Citations

19
Spiro-C(sp 3 )-atom transfer: Creating rigid three-dimensional structures with Ph 2 SCN 2 DOI
Qiu Sun,

Jan-Niklas Belting,

Julian Hauda

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6736), P. 885 - 892

Published: Feb. 20, 2025

The introduction of a single C-atom into organic substrates typically results in the formation flat molecules containing unsaturated C(sp)-centers. Adding C(sp3)-atom surrounded by four σ-C-C bonds, which opens up three-dimensional space, is an unresolved problem synthetic chemistry. We report synthesis and application diazosulfur ylide Ph2S=C=N2 reagent that combines reactivity both sulfur ylides diazo compounds to create carbon spiro-centers general fashion sequential or single-step installation C(sp3)-atom. New C-C C-X (where X O N) bonds can be created around C(sp3)-atom, ultimately extended σ-bonds one step without resorting transition metal catalysis. Ph2SCN2 also used access highly strained frameworks (oxa)spiro[2.2]pentanes as well tricyclic spiro-compounds.

Language: Английский

Citations

3
Enantioselective synthesis of 2-substituted bicyclo[1.1.1]pentanes via sequential asymmetric imine addition of bicyclo[1.1.0]butanes and skeletal editing DOI

Jinteng Che,

Wei‐Yi Ding, Hongbo Zhang

et al.

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

2
Ring Expansion toward Fused Diazabicyclo[3.1.1]heptanes through Lewis Acid Catalyzed Highly Selective C−C/C−N Bond Cross‐Exchange Reaction between Bicyclobutanes and Diaziridines DOI
Heng-Xian He, Feng Wu, Xu Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Abstract The synthesis of bicyclic scaffolds has garnered considerable interest in drug discovery because their ability to mimic benzene bioisosteres. Herein, we introduce a new approach that utilizes Lewis acid (Sc(OTf) 3 )‐catalyzed σ‐bond cross‐exchange reaction between the C−C bond bicyclobutanes and C−N diaziridines produce multifunctionalized medicinally interesting azabicyclo[3.1.1]heptane derivatives. proceeds well with different broad range aryl‐ as alkenyl‐, but also alkyl‐substituted (up 98 % yield). Conducting scale‐up experiment exploring synthetic transformations cycloadducts emphasized practical application synthesis. Furthermore, zinc‐based chiral catalytic system was developed for enantioselective version this 96 ee ).

Language: Английский

Citations

9
Stereoselective Synthesis of Highly Functionalized Bicyclo[2.1.0]pentanes by Sequential [2 + 1] and [2 + 2] Cycloadditions DOI Creative Commons
Brockton Keen,

Christina Cong,

Alberto Castanedo

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

This study describes a method for the stereoselective synthesis of highly functionalized bicyclo[2.1.0]pentanes (housanes). The approach utilizes two-step sequence, silver- or gold-catalyzed cyclopropenation alkynes followed by an intermolecular [2 + 2] photocycloaddition reaction with electron-deficient alkenes. is established aryldiazoacetates. A regioselective cycloaddition cyclopropane was developed using blue LED irradiation, commercially available photocatalyst as triplet-sensitizer, and low temperature (−40 °C). diastereoselective, when enantioenriched cyclopropenes are used, it proceeds enantioretention.

Language: Английский

Citations

1
Pyridine indole hybrids as novel potent CYP17A1 inhibitors DOI Creative Commons
Tomasz M. Wróbel, Angelika Grudzińska, Jibira Yakubu

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: Feb. 14, 2025

Prostate cancer (PCa) is one of the most prevalent malignancies affecting men worldwide, and androgen deprivation therapy (ADT) a primary treatment approach. CYP17A1 inhibitors like abiraterone target steroidogenic pathway to reduce levels, but their clinical efficacy limited by drug resistance adverse effects. This study reports synthesis evaluation novel derived from previously identified hit compound. Several analogs were synthesised, including an unexpected di-cyano derivative, which demonstrated increased potency against compared abiraterone. Biological assays revealed that these compounds significantly inhibited enzymatic activity altered steroid biosynthesis. Among newly synthesised inhibitors, compound 11 showed highest (IC50 = 4 nM) related 14 presented template for further development. A combined docking molecular dynamics approach was used identify possible binding modes compounds.

Language: Английский

Citations

1
Difunctionalization of bicyclo[1.1.0]butanes enabled by merging C−C cleavage and ruthenium-catalysed remote C−H activation DOI Creative Commons
Shan Chen,

Zhimin Xu,

Binbin Yuan

et al.

Nature Synthesis, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

Citations

1
Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity DOI
Pablo Garrido-García, Irene Quirós, Paula Milán-Rois

et al.

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

Citations

1
Palladium-catalyzed enantioselective [2σ + 2π] cycloadditions of vinyl-carbonyl-bicyclo[1.1.0]butanes with arylidenemalononitriles DOI

Tianzhu Qin,

Weiwei Zi

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111072 - 111072

Published: March 1, 2025

Language: Английский

Citations

1
Lewis acid-catalyzed (3+2) annulation of bicyclobutanes with ynamides: Access to 2-amino bicyclo[2.1.1]hexenes DOI Creative Commons

Deeptanu Sarkar,

Shiksha Deswal,

Rohan Chandra Das

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Strain-release driven annulations with bicyclo[1.1.0]butanes (BCBs) have become an attractive area of research for the synthesis bioisosteric bicyclohexane derivatives, which play a vital role in drug discovery. Interestingly, utilization inherent strain BCBs functionalized amino-bicyclo[2.1.1]hexenes, may spatially mimic substituted benzenes and anilines, has received only scant attention. Herein, we report Sc(OTf)

Language: Английский

Citations

7