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The first example of free amine γ-C(sp 3 )-H fluorination is realized using 2-hydroxynicotinaldehyde as the transient directing group. A wide range of cyclohexyl and linear aliphatic amines could be fluorinated selectively at the γ-methyl and methylene positions. Electron withdrawing 3,5-disubstituted pyridone ligands were identified to facilitate this reaction. Computational studies suggest that the turnover determining step is likely the oxidative addition step for methylene fluorination, while it is likely the C-H activation step for methyl fluorination. The explicit participation of Ag results in a lower energetic span for methylene fluorination and a higher energetic span for methyl fluorination, which is consistent with the experimental observation that the addition of silver salt is desirable for methylene but not for methyl fluorination. Kinetic studies on methyl fluorination suggest that the substrate and PdL are involved in the rate-determining step, indicating that the C-H activation step may be partially rate-determining. Importantly, an energetically preferred pathway has identified an interesting pyridone-assisted bimetallic transition state for the oxidative addition step in methylene fluorination, thus uncovering a potential new role of the pyridone ligand.

The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were explored in the context of C-28 amide substituents. Compared to the C-28 amide series, the C-28 amine derivatives exhibited further improvements in HIV-1 inhibitory activity toward polymorphisms in the Gag polyprotein as well as improved activity in the presence of human serum. However, plasma exposure of basic amines following oral administration to rats was generally low, leading to a focus on moderating the basicity of the amine moiety distal from the triterpene core. The thiomorpholine dioxide (TMD) 20 emerged from this study as a compound with the optimal antiviral activity and an acceptable pharmacokinetic profile in the C-28 amine series. Compared to the C-28 amide 3, 20 offers a 2- to 4-fold improvement in potency towards the screening viruses, exhibits low shifts in the EC 50 values toward the V370A and ΔV370 viruses in the presence of human serum or human serum albumin, and demonstrates improved potency towards the polymorphic T371A and V362I virus variants., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pd(II)-catalyzed γ-C(sp 3 )-H arylation of primary amines is realized by using 2-hydroxynicotinaldehyde as a catalytic transient directing group. Importantly, the catalyst and the directing group loading can be lowered to 2% and 4% respectively, thus demonstrating high efficiency of this newly designed transient directing group. Heterocyclic aryl iodides are also compatible with this reaction. Furthermore, swift synthesis of 1,2,3,4-tetrahydronaphthyridine derivatives is accomplished using this reaction.

A new synthesis of indole derivatives has been achieved through intramolecular dehydrative coupling of tertiary amines and ketones promoted by KO-t-Bu/DMF. The reaction probably proceeds via an α-amino alkyl radical pathway.

Nitrogen heterocycles could be prepared in good yields via intramolecular cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF.

The NH(2) group in primary allylic amines was substituted directly by sulfinate salts with excellent regio- and stereoselectivities. In the presence of 0.1 mol % [Pd(allyl)Cl](2), 0.4 mol % 1,4-bis(diphenylphosphino)butane (dppb), and excess boric acid, a range of α-unbranched primary allylic amines were smoothly substituted with sodium sulfinates in an α-selective fashion to give structurally diverse allylic sulfones in good to excellent yields with exclusive E selectivity. Replacing dppb with 1,1'-bi-2-naphthol (BINOL) allowed unsymmetric α-chiral primary allylic amines to be transformed into the corresponding allylic sulfones in good to excellent yields with excellent retention of ee. Importantly, the reaction complements known asymmetric methods in substrate scope via its unique ability to provide α-chiral allylic sulfones with high optical purity starting from unsymmetric allylic electrophiles.

Choline metabolite trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found that the TMAO levels in peripheral and cord plasma were increased in women with GDM and that TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion, and angiogenesis of HTR-8/Svneo cells. However, TMAO not only could inhibit the formation of NETs but also could enhance the biological function of HTR-8/Svneo cells. With induction of GDM in NETs-deficient PAD4-/- and wild-type mice, the placental weight of PAD4-/- mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicate that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO not only could promote the development of the placenta and fetuses but also could inhibit the formation of NETs. [ABSTRACT FROM AUTHOR]

An efficient approach has been developed for the construction of quinazolin-4(3 H)-ones by the selective anodic dehydrogenative oxidation/cyclization of benzylic chlorides and 2-aminobenzamides. The method features acceptor-free and metal-free dehydrogenation of amines to imines; a subsequent intermolecular addition provides the products in moderate to good yields. [ABSTRACT FROM AUTHOR]

Materials with hysteretic multi-step spin-crossover (SCO) have potential application in high-order data storage. Here, an unprecedented hysteretic four-step SCO behavior with the sequence of LS↔HS0.25LS0.75↔HS0.5LS0.5↔ HS0.75LS0.25↔HS is found in a three-dimensional (3D) Hofmann-type metal-organic framework (MOF), which is evidenced by magnetic, differential scanning calorimetry, and crystal data. Further experiments involving guest exchange leads to the first reversible modulation of four-, two-, and one-stepped SCO behaviors, which provides a new strategy for developing multi-step SCO materials. [ABSTRACT FROM AUTHOR]

Pain is one of the most challenging and stressful conditions to patients with sickle cell disease (SCD) and their clinicians. Patients with SCD start experiencing pain as early as 3 months old and continue having it throughout their lives. Although many aspects of the disease are well understood, little progress has been made in understanding and treating pain in SCD. This study aimed to investigate the functional involvement of Ca/calmodulin-dependent protein kinase II (CaMKIIα) in the persistent and refractory pain associated with SCD. We found that nonevoked ongoing pain as well as evoked hypersensitivity to mechanical and thermal stimuli were present in Berkeley sickle cell transgenic mice (BERK mice), but not nonsickle control littermates. Prominent activation of CaMKIIα was observed in the dorsal root ganglia and spinal cord dorsal horn region of BERK mice. Intrathecal administration of KN93, a selective inhibitor of CaMKII, significantly attenuated mechanical allodynia and heat hyperalgesia in BERK mice. Meanwhile, spinal inhibition of CaMKII elicited conditioned place preference in the BERK mice, indicating the contribution of CaMKII in the ongoing spontaneous pain of SCD. We further targeted CaMKIIα by siRNA knockdown. Both evoked pain and ongoing spontaneous pain were effectively attenuated in BERK mice. These findings elucidated, for the first time, an essential role of CaMKIIα as a cellular mechanism in the development and maintenance of spontaneous and evoked pain in SCD, which can potentially offer new targets for pharmacological intervention of pain in SCD. [ABSTRACT FROM AUTHOR]

Primary allylic amines serve as suitable allylic electrophiles for the allylation reactions of hypophosphorous acid and H-phosphinic acids. In the presence of tris(dibenzylideneacetone)dipalladium(0) ([Pd2(dba)3], 0.1 mol %) and Xantphos (0.2 mol %), aqueous hypophosphorous acid was allylated by α-unbranched primary allylic amines in a highly regioselective fashion to give structurally diverse allylic H-phosphinic acids in good to excellent yields with exclusive E selectivity. Moreover, increasing the catalyst loading to 1 mol % and adding aqueous phosphoric acid (1.2 equiv.) permitted the allylation of H-phosphinic acids with α-unbranched primary allylic amines to proceed to give disubstituted phosphinic acids in good to excellent yields. [ABSTRACT FROM AUTHOR]

ABSTRACT Dodecyl amine functionalized graphene oxide (DA-GO)/isotactic polypropylene (iPP) nanocomposites were prepared via solution mixing method. Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) verified that the DA was successfully grafted onto the surface of graphene oxide. The crystallization behavior of iPP/DA-GO nanocomposites was investigated by differential scanning calorimetry (DSC) and polarized optical microscope (POM). The DSC results of both isothermal and non-isothermal crystallization process indicated that the addition of DA-GO can decrease the half-time crystallization ( t1/2) and elevate crystallization peak temperature ( T p) of iPP. The results of isothermal crystallization kinetics showed that the overall crystallization rates of iPP/DA-GO nanocomposites, especially with higher DA-GO content, were much faster than that of neat iPP. During the non-isothermal crystallization process, the nucleation ability (Φ) of nanocomposites containing 0.05, and 0.5 wt % DA-GO were 0.83 and 0.69, respectively. And the crystallization activation energy [ABSTRACT FROM AUTHOR]

A series of novel hindered amine light stabilizers (HALSs) containing four hindered amine groups were designed and synthesized from diamines, methyl acrylate, and 2,2,6,6-pentamethyl-piperidine-4-ol through Michael addition and transesterification. The structures of target compounds were confirmed by 1H NMR and 13C NMR. Two of them were chosen to be evaluated for their antioxidation and anti-aging properties, compared with HALS tinuvin 770, chimassorb 944, tinuvin 622, antioxidant irganox B215, and irganox B225 in polypropylene (PP) and polyethylene (PE), and the results indicated that their oxidation resistance and photostabilization efficiency were better than HALS tinuvin 770, chimassorb 944, rinuvin 622, and antioxidant irganox B215. [ABSTRACT FROM AUTHOR]

The binary system studied was monoethanolamine(MEA)+2-piperidineethanol (2-PE). Heat capacities of aqueous mixtures of MEA with 2-PE were measured from 30 to 80 °C with a differential scanning calorimeter (DSC). For mole fractions of water ranging from 0.2 to 0.8, 16 concentrations of the MEA+2-PE+water systems were studied. An excess molar heat capacity expression, using the Redlich–Kister equation for the composition dependence, is used to represent the measured Cp of alkanolamine aqueous solutions. The results of heat capacity calculation (overall average absolute percentage deviation) for a total of 176 data points for MEA+2-PE+water system are 0.2 and 7.4% for molar heat capacity and excess molar heat capacity, respectively. The heat capacity values of aqueous mixtures of MEA with 2-PE presented in this study are, in general, of sufficient accuracy for most engineering-design calculations when using MEA+2-PE+water as absorbent for acid gas removal process. [Copyright &y& Elsevier]

Further hydrolysis of the title intermediates provides tetrahydropyridines in high yields and with high diastereo- and enantioselectivities. [ABSTRACT FROM AUTHOR]

The 6-endo-cyclization of substrates (VI) and (VIII) gives rise to corresponding tetrahydroquinoline derivatives, whilst the reaction of substrate (XI) leads to indoline (XII) as a result of a 5-exo-cyclization. [ABSTRACT FROM AUTHOR]

Optimized conditions render possible the efficient allylation of hypophosphorous acid and H-phosphinic acids with various primary amines. [ABSTRACT FROM AUTHOR]