Highly Stereoselective Synthesis of Trisubstituted cis-[3]Cumulenols from Alkynylated Oxatitanacycles in the Presence of Lewis acids

A highly efficient and stereoselective method for the synthesis of trisubstituted cis-[3]cumulenols via oxatitanacycles derived from titanium-mediated coupling of 1,3-butadiynes with aldehydes or ketones promoted by Lewis-acids is described

Highly Stereoselective Synthesis of Trisubstituted cis-[3]Cumulenols from Alkynylated Oxatitanacycles in the Presence of Lewis acids

A highly efficient and stereoselective method for the synthesis of trisubstituted cis-[3]cumulenols via oxatitanacycles derived from titanium-mediated coupling of 1,3-butadiynes with aldehydes or ketones promoted by Lewis-acids is described

Highly Stereoselective Synthesis of Trisubstituted cis-[3]Cumulenols from Alkynylated Oxatitanacycles in the Presence of Lewis acids

A highly efficient and stereoselective method for the synthesis of trisubstituted cis-[3]cumulenols via oxatitanacycles derived from titanium-mediated coupling of 1,3-butadiynes with aldehydes or ketones promoted by Lewis-acids is described

Carbon−Carbon Bond Formation of α-Alkynylzirconacyclopentenes via Cyclization or a Cu/Pd-Mediated Cyclization/Cross-Coupling Sequence with Aryl Iodides

The cyclization of α-alkynylzirconacyclopentenes in the presence of CuCl was achieved cleanly to afford stereodefined 3-ylidenecyclopentenes. Coupling of the copper intermediates with a variety of aryl iodides catalyzed by Pd(PPh3)4 afforded bis-arylated ylidenecyclopentenes; however, in the absence of copper salts, the coupling reaction of the same zirconacycles with aryl iodides was efficiently promoted by Pd(OAc)2/PPh3 in toluene to afford the monoarylated products. Activation of the central double bond of the cumulenic intermediate by a Pd(II) complex followed by nucleophilic attack of the Zr−sp3 carbon bond to form an alkenylpalladium intermediate accounting for this novel cyclization is suggested

Carbon−Carbon Bond Formation of α-Alkynylzirconacyclopentenes via Cyclization or a Cu/Pd-Mediated Cyclization/Cross-Coupling Sequence with Aryl Iodides

The cyclization of α-alkynylzirconacyclopentenes in the presence of CuCl was achieved cleanly to afford stereodefined 3-ylidenecyclopentenes. Coupling of the copper intermediates with a variety of aryl iodides catalyzed by Pd(PPh3)4 afforded bis-arylated ylidenecyclopentenes; however, in the absence of copper salts, the coupling reaction of the same zirconacycles with aryl iodides was efficiently promoted by Pd(OAc)2/PPh3 in toluene to afford the monoarylated products. Activation of the central double bond of the cumulenic intermediate by a Pd(II) complex followed by nucleophilic attack of the Zr−sp3 carbon bond to form an alkenylpalladium intermediate accounting for this novel cyclization is suggested

Carbon−Carbon Bond Formation of α-Alkynylzirconacyclopentenes via Cyclization or a Cu/Pd-Mediated Cyclization/Cross-Coupling Sequence with Aryl Iodides

The cyclization of α-alkynylzirconacyclopentenes in the presence of CuCl was achieved cleanly to afford stereodefined 3-ylidenecyclopentenes. Coupling of the copper intermediates with a variety of aryl iodides catalyzed by Pd(PPh3)4 afforded bis-arylated ylidenecyclopentenes; however, in the absence of copper salts, the coupling reaction of the same zirconacycles with aryl iodides was efficiently promoted by Pd(OAc)2/PPh3 in toluene to afford the monoarylated products. Activation of the central double bond of the cumulenic intermediate by a Pd(II) complex followed by nucleophilic attack of the Zr−sp3 carbon bond to form an alkenylpalladium intermediate accounting for this novel cyclization is suggested

Highly Efficient Synthesis of Functionalized Indolizines and Indolizinones by Copper-Catalyzed Cycloisomerizations of Propargylic Pyridines

The copper-catalyzed cycloisomerizations of 2-pyridyl-substituted propargylic acetates and its derivatives are described, which offer an efficient route to C-1 oxygenated indolizines with a wide range of substituents under mild reaction conditions. The presented method could be readily applied to the synthesis of indolizinones through a cyclization/1,2-migration of tertiary propargylic alcohols

Highly Efficient Synthesis of Functionalized Indolizines and Indolizinones by Copper-Catalyzed Cycloisomerizations of Propargylic Pyridines

The copper-catalyzed cycloisomerizations of 2-pyridyl-substituted propargylic acetates and its derivatives are described, which offer an efficient route to C-1 oxygenated indolizines with a wide range of substituents under mild reaction conditions. The presented method could be readily applied to the synthesis of indolizinones through a cyclization/1,2-migration of tertiary propargylic alcohols

Highly Efficient Synthesis of Functionalized Indolizines and Indolizinones by Copper-Catalyzed Cycloisomerizations of Propargylic Pyridines

The copper-catalyzed cycloisomerizations of 2-pyridyl-substituted propargylic acetates and its derivatives are described, which offer an efficient route to C-1 oxygenated indolizines with a wide range of substituents under mild reaction conditions. The presented method could be readily applied to the synthesis of indolizinones through a cyclization/1,2-migration of tertiary propargylic alcohols

A Lamin-Binding Ligand Inhibits Homologous Recombination Repair of DNA Double-Strand Breaks

Nuclear lamins are type V intermediate filament proteins. Lamins, including LA, LB1, LB2, and LC, are the major protein components forming the nuclear lamina to support the mechanical stability of the mammalian cell nucleus. Increasing evidence has shown that LA participates in homologous recombination (HR) repair of DNA double-strand breaks (DSBs) . However, the mechanisms underlying this process are incompletely understood. We recently identified the first lamin-binding ligand 1 (LBL1) that directly binds LA and inhibited cancer cell growth. We provided here further mechanistic investigations of LBL1 and revealed that LA interacts with the HR recombinase Rad51 to protect Rad51 from degradation. LBL1 inhibits LA–Rad51 interaction leading to accelerated proteasome-mediated degradation of Rad51, culminating in inhibition of HR repair of DSBs. These results uncover a novel post-translational regulation of Rad51 by LA and suggest that targeting the LA–Rad51 axis may represent a promising strategy to develop cancer therapeutics