A palladium‐catalyzed asymmetric intramolecular allylic C−H amination controlled by a chiral phosphoramidite ligand was established for the preparation of various substituted chiral ...hydropyrimidinones, the precursors of hydropyrimidines, in high yields with high enantioselectivities. In particular, dienyl sodium N‐sulfonyl amides bearing an arylethene‐1‐sulfonyl group underwent a sequential allylic C−H amination and intramolecular Diels–Alder (IMDA) reaction to produce chiral fused tricyclic tetrahydropyrimidinone frameworks in high yields and with high levels of stereoselectivity. Significantly, this method was used as the key step in an asymmetric synthesis of letermovir.
Getting to the core of it: An asymmetric palladium‐catalyzed intramolecular allylic C−H amination controlled by a chiral phosphoramidite ligand was used to provide efficient access various substituted chiral hydropyrimidines. This methodology was successfully applied to the asymmetric synthesis of letermovir (see scheme; IMDA=intramolecular Diels–Alder reaction).
Branched selectivity in asymmetric allylic C−H alkylation is enabled by using 2‐acylimidazoles as nucleophiles in the presence of a chiral phosphoramidite‐palladium catalyst. A wide range of terminal ...alkenes, including 1,4‐dienes and allylarenes, are nicely tolerated and provide chiral 2‐acylimidazoles in moderate to high yields and with high levels of regio‐, and enantio‐, and E/Z‐selectivities. Mechanistic studies using density‐functional theory calculations suggest a nucleophile‐coordination‐enabled inner‐sphere attack mode for the enantioselective carbon–carbon bond‐forming event.
Branching out: Palladium‐chiral phosphoramidite catalysis is used for an unprecedented branched‐selective asymmetric allylic C−H alkylation by using 2‐acylimidazoles as model coordinating nucleophiles. Density‐functional theory calculations suggest an unusual inner‐sphere mechanism for the carbon–carbon bond‐forming process.
The asymmetric allylic alkylation (AAA), which features employing active allylic substrates, has historical significance in organic synthesis. The allylic C–H alkylation is principally more atom- and ...step-economic than the classical allylic functionalizations and thus can be considered a transformative variant. However, asymmetric allylic C–H alkylation reactions are still scarce and yet underdeveloped. Herein, we have found that Z/E- and regioselectivities in the Pd-catalyzed asymmetric allylic C–H alkylation of 1,4-dienes are highly dependent on the type of nucleophiles. A highly stereoselective allylic C–H alkylation of 1,4-dienes with azlactones has been established by palladium-chiral phosphoramidite catalysis. The protocol proceeds under mild conditions and can accommodate a wide scope of substrates, delivering structurally divergent α,α-disubstituted α-amino acid surrogates in high yields and excellent levels of diastereo-, Z/E-, regio-, and enantioselectivities. Notably, this method provides key chiral intermediates for an efficient synthesis of lepadiformine marine alkaloids. Experimental and computational studies on the reaction mechanism suggest a novel concerted proton and two-electron transfer process for the allylic C–H cleavage and reveal that the Z/E- and regioselectivities are governed by the geometry and coordination pattern of nucleophiles.
A highly regio- and enantioselective allylic C-H alkylation of 1,4-dienes with glycine Schiff bases has been established by chiral palladium-phosphoramidite catalysis. This reaction can proceed under ...mild conditions and tolerate a wide scope of 1,4-dienes, delivering structurally diverse chiral β-branched a-amino acid surrogates in moderate to high yields and with high levels of regio-,
Z
/
E
-, diastereo- and enantioselectivities.
Asymmetric functionalization of the C(sp3)–H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with ...minimal manipulation of functional groups. Here, we report an asymmetric C(sp3)–H/C(sp3)–H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C–H bond, effectively complementing established methodology for allylic C–H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.
Previous studies have shown that intermittent hypobaric hypoxia (IH) preconditioning protected neurons survival from brain ischemia. However, the mechanism remains to be elucidated. The present study ...explored the role of nitric oxide (NO) in the process by measuring the expression of NO synthase (NOS) and NO levels. Male Wistar rats (100) were randomly assigned into four groups: sham group, IH + sham group, ischemia group and IH + ischemia group. Rats for IH preconditioning were exposed to hypobaric hypoxia mimicking 5000 m high-altitude (P
B
= 404 mmHg, PO
2
= 84 mmHg) 6 h/day, once daily for 28 days. Global brain ischemia was established by four-vessel occlusion that has been created by Pulsinelli. Rats were sacrificed at 7th day after the ischemia for neuropathological evaluation by thionin stain. In addition, the expression of neuronal NOS (nNOS), inducible NOS (iNOS), and NO content in the hippocampal CA1 subfield were measured at 2nd day and 7th day after the ischemia. Results revealed that global brain ischemia engendered delayed neuronal death (DND), both nNOS and iNOS expression up-regulated, and NO content increased in the hippocampal CA1 subfield. IH preconditioning reduced neuronal injury induced by the ischemia, and prevented the up-regulation of NOS expression and NO production. In addition,
l
-NAME + ischemia group was designed to detect whether depressing NO production could alleviate the DND. Pre-administration of
l
-NAME alleviated DND induced by the ischemia. These results suggest that IH preconditioning plays a protective role by inhibiting the over expression of NOS and NO content after brain ischemia.
An asymmetric allylic C–H alkylation of allyl ethers has been established by chiral phosphoramidite-palladium catalysis, affording a wide variety of functionalized chiral 2-acylimidazoles in moderate ...to high yields and with high levels of enantioselectivity. Moreover, this protocol could be applied to a concise asymmetric synthesis of a tachykinin receptor antagonist.
Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown ...potential in asymmetric radical reactions that have long eluded small-molecule catalysts
. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes
. Here we report photobiocatalytic asymmetric sp
-sp
oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5'-phosphate-dependent enzymes, threonine aldolases
, for the α-C-H functionalization of glycine and α-branched amino acid substrates by a radical mechanism, giving rise to a range of α-tri- and tetrasubstituted non-canonical amino acids
possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp
-sp
oxidative coupling
, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology.
Abstract
Background
In tibial plateau fractures, the posterolateral segment of the tibia plateau is frequently affected and challenging to treat. Although there are many surgical approaches and ...fixation methods for the treatment of these fractures, all of these methods have
limitations
. We designed a new rotational support plate (RSP) and a special pressurizer that can fix the fracture directly via the anterolateral approach. This method is advantageous because it leads to little trauma, involves a simple operation, and has a reliable fixation effect. This study details the technique of treating these fractures with the RSP and special pressurizer and provides the outcomes.
Methods
From May 2016 to January 2019, the data of 12 patients with posterolateral tibial plateau fractures treated with the RSP and special pressurizer in our hospital were retrospectively analyzed. Postoperative rehabilitation was advised, knee X-rays were taken at follow-ups, and fracture healing, complications, and knee range of motion were assessed. The Hospital for Special Surgery (HSS) knee score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to evaluate knee function at the last follow-up.
Results
The average follow-up time of all patients was 16.5 months (range, 12–25 months). The average bony union time was 3.2 months (range, 3–4.5 months). At the last follow-up, the average knee range of motion was 138° (range, 107–145°). The average HSS score was 91 (range, 64–98). The average KOOS Symptoms score was 90 (range, 75–96). The average KOOS Pain score was 91 (range, 72–97). The average KOOS ADL score was 91 (range, 74–97). The average KOOS sport/recreation score was 83 (range, 70–90). The average KOOS QOL score was 88 (range, 69–93). Skin necrosis, incision infections, and fixation failure did not occur during the follow-up period.
Conclusions
With our newly designed RSP and special pressurizer, posterolateral tibial plateau fractures can be easily and effectively reduced and fixed through the anterolateral approach, which serves as a novel treatment for posterolateral tibial plateau fractures.
The design of flame-retardant cellulose fabrics suffered from deterioration on wearing performance and environmental issue. Here, we developed facile construction of bio-based high fire-safety ...cellulose fabrics (lyocell) that exploited the bio-based flame-retardant coating (APD) by adenosine triphosphate (ATP) and dicyandiamide (DCD) via ionic reaction. The rich phosphorus/nitrogen elements of APD enabled the excellent fire safety of APD/Lyocell. Specifically, the APD/Lyocell2 had a higher limiting oxygen index (LOI) value of 29.3 %, a lower peak of heat release rate (PHRR, decreasing by 66.6 %), and a reduced total heat rate (THR, lowered by 56.5 %) with respect to pure lyocell fabrics. Interestingly, the APD/Lyocell2 exhibited well flame-retardant durability via passing the vertical burning test after 100 rubs. The satisfactory flame-retardant behaviors of APD/Lyocell derived from the excellent synergistic effect on the gaseous-solid phases, where APD could release more non-flammable gasses and generate phosphoric acid, polyphosphoric acid, etc. to accelerate itself and cellulose dehydration into char residues during combustion. More importantly, the wearing performance of APD/Lyocell fabrics, such as handle, air permeability and tensile strength, etc. almost remained after treatment. The ease of operation and use of bio-based coating made it a promising option to obtain the practical lyocell fabrics with flame-retardancy.
•The high fire-safety lyocell fabrics with the bio-based flame-retardant coating was facile construction by ionic reaction.•APD/Lyocell presented satisfactory fire safety.•The wearing performance of APD/Lyocell almost remained with respect to pure lyocell fabrics.
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