Advancing Meta-Selective C-H Amination through Non-Covalent Interactions.

Regioselective C-H amination of simple arenes is highly desirable, but accessing meta-sites of ubiquitous arenes has proven challenging due to the lack of both electronic and spatial preference. This study demonstrates the successful use of various privileged nitrogen-containing functionalities found in pharmaceutical compounds to direct meta-C-H amination of arenes, overcoming the long-standing requirement for a redundant directing group. The remarkable advancements in functional group accommodation for precise regiochemical control were achieved through the discovery of an unprecedented organo-initiator and the strategic utilization of non-covalent interactions. This protocol has been successfully applied in the concise synthesis and late-stage derivatization of drug molecules, which would have been otherwise challenging to achieve.

The effects of different types of Tai Chi exercises on motor function in patients with Parkinson's disease: A network meta-analysis.

Background: Tai Chi can show improvement in balance and motor ability of elderly patients with PD. However, there were few reports on differences in outcomes associated with different types of Tai Chi on improving exercise capacity in elderly patients with PD. We compared the improvement of motor function in Parkinson's patients with different types of Tai Chi, for finding an optimal intervention. Methods: The following databases were searched from the beginning of the establishment of each database to 10 January 2022: PubMed, EMBASE, The Cochrane Library, CNKI, Wanfang Database, and VIP Database. Randomized controlled trials incorporating different types of Tai Chi for PD were included. The outcome measures were UPDRSIII and BBS. NMA was conducted using Stata 15.0 based on a frequentist framework. Results: A total of twenty trials were eligible, including 996 participants. In conventional meta-analysis, as for the UPDRSIII scale, 24-form simplified Tai Chi (SMD = -1.272, 95% CI [-2.036, -0.508], P < 0.05, I2 > 50%), Tai Chi exercise program (SMD = -0.839, 95% CI [-1.828, 0.151], P > 0.05, I2 > 50%), 8-form simplified Yang style Tai Chi (SMD = -0.325, 95% CI [-1.362, 0.713], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (SMD = -0.28, 95% CI [-0.97, 0.42], P > 0.05, I2 > 50%) were statistically more efficient than the control group. For BBS outcome, 24-form simplified Tai Chi (MD = 3.979, 95% CI [3.364, 4.595], P < 0.05, I2 <50%), Tai Chi exercise program (MD = 5.00, 95% CI [2.07, 7.93], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (MD = 1.25, 95% CI [0.52, 1.98], P < 0.05, I2 > 50%) were better than the control group. In the network meta-analysis, the results of UPDRSIII were as follows: 24-form > TCEP > 8-form YS > 8-form CS > control. The ranking probability of BBS was as follows: TCEP > 24-form > 8-form CS > control. Conclusion: Among the four treatments studied, 24-form Tai Chi and Tai Chi exercise programs have shown better efficacy than other types. Our study provides new insights into exercise therapy for PD and may contribute to the formulation of a clinical exercise prescription. Systematic review registration: Identifier: CRD42021285005.

Baduanjin exercise in the treatment of hypertension: A systematic review and meta-analysis.

Background: As a therapy to prevent and treat hypertension, exercise is widely used in clinical practice. But due to the lack of documentary evidence, Baduanjin as a relaxed and convenient mode of exercise is not currently recommended by professional health organizations to treat hypertension. The purpose of this article is to examine the efficacy of Baduanjin as an antihypertensive exercise therapy. Methods: Our systematic retrieved of the entire relevant literatures in 12 databases. Finally, 28 eligible trials involving Baduanjin intervention in hypertension were included. After the quality assessment and bias risk assessment of the included trials, we analyzed the blood pressure values before and after the intervention, and performed meta-analysis on the random effect results. In order to explore the factors influencing the decrease of blood pressure, we also performed a subgroup analysis of the results. Results: Participants (n = 2121) were adults (61.74 ± 5.85years of age, mean ± SD), with baseline blood pressure (systolic blood pressure (SBP) = 150.7 ± 9.2 mmHg, diastolic blood pressure (DBP) = 93.2 ± 8.8 mmHg). Baduanjin was practiced 7.5 ± 3.8 sessions / week for 28.2 ± 12.8 min /session for 16.7 ± 9.2 weeks. Overall, Baduanjin resulted in SBP (-9.3 mmHg, d = -1.49, 95%CI: -1.73 to -1.13) and DBP (-6.3 mmHg, d = -1.20, 95%CI: -1.51 to -0.88) vs. the control group (p < 0.001). After a subgroup analysis of age, we found that SBP heterogeneity was significantly reduced in the elderly group. Conclusion: Our results indicate that Baduanjin can effectively reduce blood pressure (i.e., 9.3 mmHg and 6.3 mmHg of SBP and DBP reductions, respectively), and reduce the incidence rate of cardiovascular disease in hypertensive patients. In addition, we will be more likely to recommend that the elderly exercise Baduanjin.

A site-selective amination catalyst discriminates between nearly identical C-H bonds of unsymmetrical disubstituted alkenes.

C-H activation reactions enable chemists to unveil new retrosynthetic disconnections and streamline conventional synthetic approaches. A long-standing challenge in C-H activation is the inability to distinguish electronically and sterically similar C-H bonds. Although numerous synergistic combinations of transition-metal complexes and chelating directing groups have been utilized to distinguish C-H bonds, undirected regioselective C-H functionalization strategies remain elusive. Here we report a regioselective C-H activation/amination reaction of various unsymmetrical dialkyl-substituted alkenes. The regioselectivity of C-H activation is correlated to the electronic properties of allylic C-H bonds indicated by the corresponding 1JCH coupling constants. A linear relationship between the difference in the 1JCH coupling constants of the two competing allylic C-H bonds (Δ1JCH) and the C-H activation barriers (ΔΔG‡) has also been determined.

Asymmetric Total Syntheses of Kopsane Alkaloids via a PtCl2 -Catalyzed Intramolecular [3+2] Cycloaddition.

A concise and asymmetric total synthesis of five kopsane alkaloids that share a unique heptacyclic caged ring system was accomplished. The key transformation in the sequence involved a remarkable PtCl2 -catalyzed intramolecular [3+2] cycloaddition, which allowed for the rapid assembly of pentacyclic carbon skeletons bearing 2,3-quaternary functionalized indoline. Expeditious construction of diverse indoline scaffolds with excellent control of diastereoselectivity demonstrated the broad scope and versatility of this key transformation.

Rhodium(III)-Catalyzed Three-Component 1,2-Diamination of Unactivated Terminal Alkenes.

We report a three-component diamination of simple unactivated alkenes using an electrophilic nitrene source and amine nucleophiles. The reaction provides rapid access to 1,2-vicinal diamines from terminal alkenes through a one-pot protocol. The transformation proceeds smoothly with excellent tolerance for a broad array of primary and secondary amines, affording the desired product with good yield and regioselectivity. The mechanism is proposed to proceed through a Rh(III)-catalyzed aziridination of alkenes with subsequent ring opening by primary or secondary amines.

A Rh(III)-Catalyzed Formal [4+1] Approach to Pyrrolidines from Unactivated Terminal Alkenes and Nitrene Sources.

We have developed a formal [4+1] approach to pyrrolidines from readily available unactivated terminal alkenes as 4-carbon partners. The reaction provides a rapid construction of various pyrrolidine containing structures, especially for the diastereoselective synthesis of spiro-pyrrolidines. Mechanistic investigation suggests a Rh(III)-catalyzed intermolecular aziridination of the alkene and subsequent acid-promoted ring expansion for the pyrrolidine formation.

Ligand Controlled Ir-Catalyzed Regiodivergent Oxyamination of Unactivated Alkenes.

An intramolecular Ir(III)-catalyzed regiodivergent oxyamination of unactivated alkenes provides valuable γ-lactams, γ-lactones and δ-lactams. The regioselectivity is controlled by the electronically tunable cyclopentadienyl Ir(III)-complexes enabling oxyamination via either 5-exo or 6-endo pathways. With respect to the mechanism, we propose a highly reactive [3.1.0] bicycle intermediate derived from Ir(V) nitrene-mediated aziridination to be a key intermediate toward the synthesis of γ-lactams.

Ir-Catalyzed Intermolecular Branch-Selective Allylic C-H Amidation of Unactivated Terminal Olefins.

An efficient method for intermolecular branch-selective allylic C-H amidation has been accomplished via Ir(III) catalysis. The reaction proceeds through initial allylic C-H activation, supported by the isolation and crystallographic characterization of an allyl-Ir(III) intermediate, followed by a subsequent oxidative amidation with readily available dioxazolones as nitrenoid precursors. A diverse range of amides are successfully installed at the branched position of terminal alkenes in good yields and regioselectivities. Importantly, the reaction allows the use of amide-derived nitrenoid precursors avoiding problematic Curtius-type rearrangements.

Enantioselective total synthesis of (-)-kainic acid and (+)-acromelic acid C via Rh(i)-catalyzed asymmetric enyne cycloisomerization.

A diversity-oriented synthetic strategy was developed for the total synthesis of kainoid amino acids, which led to the enantioselective synthesis of (-)-kainic acid and the first total synthesis of (+)-acromelic acid C. Rh(i)-catalyzed asymmetric enyne cycloisomerization served as the key reaction in this strategy for the rapid construction of highly functionalized lactam, and the resulting vinyl acetate moiety was further utilized as a versatile building block for the installation of both isopropylidene and 2-pyridone units existing in natural kainoids.

Regio- and Stereospecific Construction of 3a-(1H-Indol-3-yl)pyrrolidinoindolines and Application to the Formal Syntheses of Gliocladins B and C.

A one-pot regio- and stereospecific strategy for the construction of 3a-(3-indolyl)-hexahydropyrrolo[2,3-b]indoles based on the condensation of an indole and an in situ generated cyclopropylazetoindoline has been developed. This unified strategy works with a variety of substituted indoles to produce 3a-(3-indolyl)hexahydropyrrolo[2,3-b]indole products in high yields. The utility of this transformation was highlighted in the formal total syntheses of gliocladins B and C.

Total synthesis and stereochemical reassignment of mandelalide A.

The total synthesis of the tunicate metabolite mandelalide A and the correction of its originally assigned stereochemistry are reported. Key features of the convergent, fully stereocontrolled route include the use of a Prins cyclization for the diastereoselective construction of the tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the preparation of the tetrahydrofuran moiety, Suzuki coupling, Horner-Wadsworth-Emmons macrocyclization, and glycosylation to append the L-rhamnose-derived pyranoside.

Total synthesis and stereochemical revision of lagunamide A.

A revised configurational assignment for the marine metabolite lagunamide A is proposed and validated by total synthesis.