Transition metal complexes with functionalized indenyl phosphine ligands: structures and catalytic properties.

Transition-metal indenyl complexes usually exhibit different reactivities compared with their cyclopentadienyl analogues. Up to now, at least 10 metal-indenyl bonding modes have been reported. Because of the "indenyl effect", transition-metal indenyl complexes usually show enhanced reactivity in substitution and related reactions. This review provides an overview on the use and impact of indenyl phosphines in organometallic chemistry and transition-metal-catalysed reactions in the recent two decades. Some cationic and zwitterionic metal complexes supported by P,N-substituted indene or indenide ligands are described. They have been reported to induce the cleavage of E-H (E = H, Si and B) bonds and can be used as catalysts for addition of E-H bonds to unsaturated substrates. 2-Aryl indenyl phosphine ligands L3-L11 have been proven to be a class of versatile ligands for palladium-catalysed C-C and C-N cross-coupling reactions. Moreover, optically active tethered indenyl phosphine ligands can have better stereoselective control over the chirality arising at the metal center in the oxidative addition of their rhodium complexes with alkyl halides.

Klotho ameliorates diabetic nephropathy by activating Nrf2 signaling pathway in podocytes.

Oxidative stress plays a key role in the pathogenesis of diabetic nephropathy (DN). The anti-aging protein Klotho has been demonstrated to have antioxidant capacity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating antioxidant responses. The present study aimed to explore the effects of Klotho on DN and the underlying mechanisms related to Nrf2. Low glucose (LG) or high glucose (HG) medium-cultured podocytes and diabetic db/db mice were overexpressed with Klotho via adenoviral transfer to evaluate the effects of Klotho on Nrf2 signaling, oxidative stress, podocyte apoptosis, and renal function and histopathology. Klotho overexpression significantly induced the expression and activation of Nrf2 as well as its downstream targets SOD2 and NQO1 in podocytes. Moreover, Klotho overexpression inhibited HG-induced oxidative stress and apoptosis in podocytes. Co-treatment with Nrf2 inhibitor trigonelline prevented Klotho-induced expression of SOD2 and NQO1, and abolished Klotho-conferred antioxidant and anti-apoptotic effects. In db/db mice, Klotho overexpression also activated Nrf2 signaling, and suppressed diabetes-induced oxidative stress and podocyte apoptosis, which were accompanied by improved renal function and decreased glomerulosclerosis. Our data highlight a novel Nrf2-mediated antioxidant mechanism underlying the protective effects of Klotho in podocytes and indicate the therapeutic potential of targeting Klotho to activate Nrf2 in DN.

Transition-Metal-Catalyzed Regioselective Functionalization of Monophosphino-o-Carboranes.

A facile approach to the synthesis of diaryl- and dialkyl-substituted monophosphino-o-carboranes by rhodium(I)-catalyzed phosphine-directed B3,6 -H activation has been developed for the first time. Upon switching rhodium(I) to palladium(II), C-arylated and B6 -halogenated products were obtained by using tBuOLi and Li2 CO3 as base, respectively. These discoveries provide some simple and efficient approaches to the modification of monophosphino-o-carboranes.

Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy.

Podocyte damage is vital for the etiopathogenesis of diabetic nephropathy (DN). Klotho (KL), a multifunctional protein, has been demonstrated to have renoprotective effects; nevertheless, the mechanism for protective effect has not been completely elucidated. Transient receptor potential cation channel subfamily C, member 6 (TRPC6), a potential target of KL, is implicated in glomerular pathophysiology. Here, we sought to determine whether KL could protect against podocyte injury through inhibiting TRPC6 in DN. We found that high glucose (HG) triggered podocyte injury as manifested by actin cytoskeleton damage along with the downregulation of KL and Synaptopodin and the upregulation of TRPC6. KL overexpression reversed HG-induced podocytes injury, whereas cotreatment with TRPC6 activator flufenamic acid (FFA) significantly abrogated the beneficial effects conferred by KL. Moreover, KL knockdown in podocytes resulted in actin cytoskeleton impairment, decreased Synaptopodin expression, and increased TRPC6 expression. In db/db mice, KL overexpression inhibited TRPC6 expression and attenuated diabetes-induced podocyte injury, which was accompanied by decreased albuminuria and ameliorated glomerulosclerosis. Our data provided novel mechanistic insights for KL against DN and highlighted TRPC6 as a new target for KL in podocytes to prevent DN.

Direct visible-light-induced synthesis of P-stereogenic phosphine oxides under air conditions.

Over the past two decades, visible-light-induced transformations have been regarded as being among the most environmentally benign and powerful strategies for constructing complex molecules and diverse synthetic building blocks in organic synthesis. However, the development of efficient photochemical processes for assembling enantiomerically pure molecules remains a significant challenge. Herein, we describe a simple and efficient visible-light-induced C-P bond forming reaction for the synthesis of P-chiral heteroaryl phosphine oxides in moderate to high yields with excellent ee values (97-99% ee). Even in the absence of transition metal or photoredox catalysts, a variety of P-chiral heteroaryl phosphine oxides, including chiral diphosphine oxide 41, have been directly obtained under air conditions. Density functional theory (DFT) calculations have shown that the reaction involves intersystem crossing and single electron transfer to give a diradical intermediate under visible light irradiation.

Synthesis of P-chiral phosphine compounds by palladium-catalyzed C-P coupling reactions.

An efficient C-P coupling reaction of enantiopure tert-butylmethylphosphine-boranes with aryl and heteroaryl halides is developed by using Pd(OAc)2/dppf as a catalyst, affording a series of (S) or (R)-P-chiral phosphines in moderate to high yields and with ee values up to 99% ee. Moreover, the reaction time could be reduced from 72 h to 6 h with increased ee values under microwave irradiation.

Visible-Light-Promoted Transition-Metal-Free Phosphinylation of Heteroaryl Halides in the Presence of Potassium tert-Butoxide.

A novel visible-light-promoted C-P bond formation reaction in the absence of both transition metal and photoredox catalysts is disclosed. By employing easily available and inexpensive heteroaryl chlorides/bromides as substrates, a variety of heteroaryl phosphine oxides were obtained in moderate to good yields. This strategy provides a simple and efficient route to heteroaryl phosphine oxides.

Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic carbene as a non-covalent organocatalyst.

We report the first asymmetric sulfa-Michael addition (SMA) reactions using a chiral N-heterocyclic carbene (NHC) as a non-covalent organocatalyst. We demonstrate that a triazolium salt derived NHC functions as an excellent Brønsted base to promote enantioselective carbon-sulfur bond formation. The reaction is applicable to a wide range of thiols and electrophilic olefins. Notably, quaternary chiral centers bearing both an S atom and a CF3 group were synthesized with excellent asymmetric control. Mechanistic studies suggest that the facial discrimination is likely to be guided by non-covalent interactions: hydrogen bonding and π-π stacking.

A highly diastereoselective and enantioselective synthesis of polysubstituted pyrrolidines via an organocatalytic dynamic kinetic resolution cascade.

Highly functionalized pyrrolidine and piperidine analogues, with up to three stereogenic centers, were synthesized in good yield (50-95%), excellent dr (single isomer), and high ee (>90%) using a Cinchona alkaloid-derived carbamate organocatalyst. High stereoselective synergy was achieved by combining a reversible aza-Henry reaction with a dynamic kinetic resolution (DKR)-driven aza-Michael cyclization. Whereas both reactions proceed with moderate enantioselectivities (50-60% for each step), high enantioselectivities are obtained for the overall products devoid of dr sacrifice.