Two F-18 radiochemistry methods to synthesize a promising transient receptor potential canonical 5 (TRPC5) radioligand.

TRPC5 is a member of the mammalian transient receptor potential (TRP) channel superfamily and it has been implicated in various physiological and pathological mechanisms of neurological and psychiatric diseases. Fluorine-18 is one of the most widely used radionuclides for PET imaging due to its favorable chemical characteristics and nuclear-physical properties. Herein, we describe two complementary radiosynthetic approaches and preliminary evaluation for [F] as a novel and promising fluorine-18 labeled radiotracer for imaging TRPC5.

Synthesis and in vivo biological characterization of six carbon-11 sigma-1 receptor radiotracers in rodent and nonhuman primate.

Six enantiomers of three racemic sigma-1 receptor (σR) ligands were resolved, and absolute configuration was determined. Their high σR potency and selectivity were determined through in vitro binding assays, further validated by molecular docking analysis. Central Nervous System Multiparameter Optimization algorithm (CNS MPO) predicts efficient brain penetration for these enantiomers.

BINAP-CuH-catalysed enantioselective allylation using alkoxyallenes to access 1,2-,-diols.

Herein, we present an economical method for highly enantioselective and diastereoselective Cu-BINAP-catalysed reductive coupling of alkoxyallenes with a range of electronically and structurally diverse ketones to afford 1,2-,-diols, using PMHS as the hydride source. This reductive coupling has also been efficiently employed in the enantioselective desymmetrization of prochiral cyclic ketones harboring quaternary centres, in high yields with exclusive diastereoselectivity. Density Functional Theory (DFT) calculations are used to elucidate that the reaction is facilitated by a kinetically favourable "open" -enolate copper-alkoxyallene conformer, occurring at a lower Gibbs free energy barrier (by 3.

Site-selective and stereoselective transformations on -quinols & -quinamines.

The intermolecular transformation of simple substrates into highly functionalized scaffolds with multiple stereogenic centers is an attractive strategy in modern organic synthesis. Prochiral 2,5-cyclohexadienones, being stable and easily accessible, are privileged key building blocks for the synthesis of complex molecules and bioactive natural products. In particular, -quinols and -quinamines are important subclasses of cyclohexadienones, having both nucleophilic and electrophilic sites, and can undergo various intermolecular cascade annulations formal cycloadditions and other transformations.

CuH-Catalyzed Enantioselective Desymmetrization of Cyclic 1,3-Diketones.

Herein, we report a CuH-catalyzed asymmetric desymmetrization of prochiral cyclopentane-1,3-diones to access cyclic 3-hydroxy ketones having an all-carbon quaternary center with high diastereoselectivity via hydrosilylation using PMHS as an inexpensive hydride source. This reaction displays high functional group tolerance including reducible alkyne, alkene, and ester groups with a broad substrate scope. The importance of chiral cyclic 3-hydroxy ketone building blocks was also demonstrated through the synthesis of (-)-estrone, the toxicodenane E core, and fused indoles.

Metal-free oxidative formal C(sp)-H arylation of cyclopentene-1,3-diones with β-naphthols.

An efficient, mild, and transition-metal free formal C(sp)-H arylation of prochiral 2,2-disubstituted cyclopentene-1,3-diones is reported. This oxidative arylation with β-naphthols proceeds base-mediated -Michael addition followed by aerial oxygen insertion and a subsequent α-hydroperoxy elimination sequence. This operationally simple and environmentally benign transformation is highly scalable and does not require any pre-functionalization.

Enantioselective Cu(I)-catalyzed borylative cyclization of enone-tethered cyclohexadienones and mechanistic insights.

The catalytic asymmetric borylation of conjugated carbonyls followed by stereoselective intramolecular cascade cyclizations with in situ generated chiral enolates are extremely rare. Herein, we report the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones. This asymmetric desymmetrization strategy has a broad range of substrate scope to generate densely functionalized bicyclic enones bearing four contiguous stereocenters with excellent yield, enantioselectivity, and diastereoselectivity.

Rh(III)-catalyzed diastereoselective cascade annulation of enone-tethered cyclohexadienones C(sp)-H bond activation.

Herein, we report highly diastereoselective arylative cyclization of enone-tethered cyclohexadienones Rh(III)-catalyzed C-H activation of -methoxybenzamides. This reaction proceeds through the formation of a five-membered rhodacycle followed by bis-Michael cascade annulation to access functionalized bicyclic scaffolds with four contiguous stereocenters with a broad substrate scope. These products have excellent functional handles, allowing further synthetic transformation to increase the structural complexity.

Diastereoselective Desymmetrization of -Quinamines through Regioselective Ring Opening of Epoxides and Aziridines.

A highly diastereoselective desymmetrization of -quinamines via regioselective ring opening of epoxides and aziridines under mild conditions has been developed. A chairlike six-membered transition state with minimized 1,3-diaxial interactions explains the relative stereoselectivity of the cyclization reaction. This transition-metal free [3 + 3] annulation reaction provides rapid access to fused bicyclic morpholines and piperazines with a tetrasubstituted carbon center in high yields.

Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones via tandem arylative cyclization.

The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.