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Transition metal‐catalyzed enantioselective C−H carbonylation with carbon monoxide, an essential and easily available C1 feedstock, remains challenging. Here, we disclosed an unprecedented enantioselective C−H carbonylation catalyzed by inexpensive and readily available cobalt(II) salt. The reactions proceed efficiently through desymmetrization, kinetic resolution, and parallel kinetic resolution, affording a broad range of chiral isoindolinones in good yields with excellent enantioselectivities (up to 92 % yield and 99 % ee). The synthetic potential of this method was demonstrated by asymmetric synthesis of biological active compounds, such as (S)‐PD172938 and (S)‐Pazinaclone. The resulting chiral isoindolinones also serve as chiral ligands in cobalt‐catalyzed enantioselective C−H annulation with alkynes to construct phosphorus stereocenter. [ABSTRACT FROM AUTHOR]

Herein, we reported the synthesis of enantioenriched N-aryl peptoid atropisomers via Pd(II)-catalyzed atroposelective C–H olefination using the easily accessible L -pyroglutamic acid (L -pGlu-OH) as the chiral ligand. A series of optically active N-aryl peptoid atropisomers were obtained in synthetically useful yields with high enantioselectivities. [ABSTRACT FROM AUTHOR]

Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (C[Cl.sub.4]). Unexpectedly, when combined with C[Cl.sub.4], CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation. While injected after C[Cl.sub.4] cessation, CNTF could improve liver function. These data suggest that CNTF could be a potential hepatoprotective agent against C[Cl.sub.4]-induced hepatic injury after the cessation of C[Cl.sub.4] exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with C[Cl.sub.4]. Key words: ciliary neurotrophic factor (CNTF), carbon tetrachloride (C[Cl.sub.4]), fatty liver, liver injury, lipid peroxidation. Resume : On a rapporte que le facteur neurotrophique ciliaire (ou CNTF pour << ciliary neurotrophic factor >>) et les analogues du CNTF ont des effets hepatoprotecteurs et qu'ils permettent d'attenuer la steatose hepatique chez les souris db/db ou auxquelles est administre un regime; a teneur elevee en matieres grasses. Comme la steatose et les lesions hepatiques sont aussi couramment provoquees par les hepatotoxines, cette etude avait pour but de verifier que le CNTF permet d'attenuer la steatose et les lesions hepatiques provoquees par le tetrachlorure de carbone (C[Cl.sub.4]). Contrairement nos attentes, l'association du C[Cl.sub.4] avec le CNTF entrainait une aggravation de la steatose et des lesions hepatiques. Le mode d'action est associe aux effets du CNTF qui entrainait une inhibition de la secretion de lipoproteines et qui nuisait considerablement la capacite des lipoproteines servir de vehicules de transport aux lipides entre le foie et la circulation. En revanche, le CNTF pouvait ameliorer le fonctionnement du foie quand il etait injecte apres avoir cesse l'administration de C[Cl.sub.4]. Ces donnees laissent entendre que le CNTF pourrait eventuellement servir d'agent hepatoprotecteur contre les lesions hepatiques provoquees par le C[Cl.sub.4] apres avoir interrompu l'exposition au C[Cl.sub.4]. Par contre, il serait interdit d'associer un traitement par le CNTF recombinant humain mutant avec le C[Cl.sub.4]. [Traduit par la Redaction] Mots-cles : facteur neurotrophique ciliaire (CNTF), tetrachlorure de carbone (C[Cl.sub.4]), steatose hepatique, lesions hepatiques, peroxydation lipidique., Introduction Nonalcoholic fatty liver disease (NAFLD) is characterized by the triglyceride (TG) accumulation within hepatocytes and ranges from simple steatosis to steatohepatitis, which often progresses into advanced fibrosis and cirrhosis [...]

The aim of the present study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seed (GSPE) in the treatment of recurrent ulcerative colitis (UC) in rats. To induce recurrent colitis, rats were instilled with 2,4,6-tri nitrobenzene sulfonic acid (TNBS) (80 mg/kg) into the colon through the cannula in the first induced phase, and then the rats were instilled a second time with TNBS (30 mg/kg) into the colon on the sixteenth day after the first induction UC. Rats were intragastrically administered GSPE (200 mg/kg) per day for 7 days after twice-induced colitis by TNBS. Sulfasalazine at 500 mg/kg was used as a positive control drug. Rats were killed 7 days after GSPE treatment. The colonic injury and inflammation were assessed by macroscopic and macroscopic damage scores, colon weight/ length ratio (mg/cm), and myeloperoxidase activity. Then, superoxide dismutase, glutathione peroxidase, inducible nitric oxide synthase (iNOS) activities, and the levels of malonyldialdehyde, glutathione, and nitric oxide in serum and colonic tissues were measured. Compared with the recurrent UC group. GSPE treatment facilitated recovery of pathologic changes in the colon after induction of recurrent colitis, as demonstrated by reduced colonic weight/length ratio and macroscopic and microscopic damage scores. The myeloperoxidase and iNOS activities with malonyldialdehyde and nitric oxide levels in serum and colon tissues of colitis rats were significantly decreased in the GSPE group compared with those in the recurrent UC group. In addition, GSPE treatment was associated with notably increased superoxide dismutase, glutathione peroxidase activities, and glutathione levels of colon tissues and serum of rats. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, and inhibiting colonic iNOS activity to reduce the production of nitric oxide. Key words: proanthocyanidins from grape seed, 2,4,6-tri nitrobenzene sulfonic acid, recurrent, ulcerative colitis, antiinflammatory, antioxidation, free radicals. La presente etude a eu pour but d'examiner l'effet therapeutique et le mecanisme des proanthocyanidines de pepin de raisin (PPR) dans le traitement de la colite ulcereuse (CU) recurrente chez les rats. Pour induire la colite recurrente. on a injecte dans le colon par une canule 80 mg/kg d'acide 2,4,6-trinitrobenzenesulfonique (TNBS) durant la premiere phase d'induction, puis 30 mg/kg le 16e jour apres l'induction. On a administre les PPR par voie intragastrique. 200 mg/kg par jour pendant 7 jours, apres la deuxieme phase d'induction de la colite. La sulfasalazine (SASP) (500 mg/kg) a servi de medicament positif temoin. On a sacrifie les rats 7 jours apres le traitement. On a evalue la lesion colique et l'inflammation par les scores de lesions macroscopiques el microscopiques, le rapport poids/longueur (mg/cm) du colon et l'activite de la myeloperoxydase. On a de plus mesure les activites de la superoxyde dismutase, de la glutathion peroxydase et de la monoxyde d'azote synthase inductible (iNOS) ainsi que les taux de malonyldialdehyde, de glutathion et de monoxyde d'azote dans le serum et les tissus coliques. Le traitement avec les PPR a facilite la normalisation des modifications pathologiques observees apres l'induction de la colite recurrente, comme demontre par une diminution du rapport poids/longueur du colon et une diminution des scores de lesions macroscopiques et microscopiques. Les activites de la myeloperoxydase et d'iNOS ainsi que les taux de malonyldialdehyde et de monoxyde d'azot dans le serum et les tissus coliques ont diminue de maniere significative chez le groupe PPR par rapport a ceux du groupe ayant une CU recurrente. Le traitement a aussi ete associe a une nette augmentation des activites de la superoxyde dismutase et de la glutathion peroxydase, ainsi que des taux de glutathion dans le serum et les tissus coliques des rats. Les PPR ont eu un effet protecteur sur la colite recurrente des rats en modifiant la reponse inflammatoire, en inhibant l'infiltration de cellules inflammatoires et les dommages oxydatifs, en favorisant la reparation des tissus leses pour diminuer le stress oxydatif colique et en inhibant l'activite iNOS colique pour reduire la production de monoxyde d'azote. Mots-cles : proanthocyanidines de pepin de raisin, acide 2,4,6-trinitroben/enesulfonique, recurrent, colite ulcereuse, anti-inflammatoire, antioxydation, radicaux libres. [Traduit par la Redaction], Introduction Inflammatory bowel diseases are chronic relapsing inflammatory disorders of the gastrointestinal tract (Geier et al. 2007). Being one of the inflammatory bowel diseases, ulcerative colitis (UC) is a disorder [...]

The aim of the study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seeds (GSPE) in the treatment of ulcerative colitis (UC). Rats were intragastrically administered different doses of GSPE (100, 200, and 400 mg/kg) per day for 7 days after UC was twice-induced by intracolonic injection of 2,4,6trinitrobenzene sulfonic acid (TNBS)dissolved in 50% ethanol. Sulfasalazine (SASP) at 200 mg/kg was used as a positive control drug. Macroscopic and microscopic damage scores and changes in weight/length ratio (mg/mm) of colon segments were analyzed. The levels of malonyldialdehyde (MDA), interleukin (IL)-1 β, IL-2, IL-4, and myeloperoxidase (MPO) activity in the colon tissues and MPO activity in the serum were all measured by biochemical methods or double antibody sandwich ELISA methods. Compared with the TNBS control group, GSPE treatment facilitated recovery of pathologic changes in the colon after insult with TNBS, as demonstrated by increased body weight (p < 0.01) and decreased colonic weight/ length ratio (p < 0.01); GSPE also notably reduced the colonic macroscopic and microscopic damage scores (p < 0.01). The MPO activity in colon tissues and serum of rats treated with GSPE was significantly lower than that in the TNBS control group. The MDA and IL-1 β levels of colon tissues were also decreased in GSPE groups. The intestinal antiinflammatory effect of GSPE was accompanied by a significant improvement of IL-2 and IL-4 levels in the colon tissues of rats in the high-dose GSPE group (p < 0.05). Compared with the SASP group, GSPE groups had no significant difference in the therapeutic effect (p > 0.05). GSPE exerts a beneficial anti-inflammatory effect in the acute phase of TNBS-induced colitis in rats by downregulating some of the mediators involved in the intestinal inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, decreasing production of proinflammatory cytokines IL-1 β, and increasing production of anti-inflammatory cytokines IL-2 and IL-4. Key words: proanthocyanidins from grape seeds, ulcerative colitis, trinitrobenzene sulfonic acid, antiinflammatory, antioxidation, interleukin. Pour examiner l'effet therapeutique et le mecanisme des proanthocyanidines extraites des graines de raisin (GSPE) chez des rats souffrant de colite ulcereuse (CU) induite par l'acide 2,4,6-trinitrobenzene sulfonique (TNBS), on leu a administre differentes doses de GSPE (100, 200 et 400 mg/kg) par voie intragastrique, tons les jours pendant 7 jours, apres que la CU a ete induite deux fois par l'injection intracolique de TNBS dissous dans de l'ethanol 50 %. La sulfasalazine (200 mg/kg, SASP) a servi de medicament temoin positif. Puis les rats ont ete sacrifies. Les scores des lesions microscopiques et macroscopiques, et les modifications de la relation poids/longueur (mg/mm) des segments de colon ont ete analyses. Les taux de malonyldyaldehyde (MDA), interleukine-1 β (IL-1β), interleukine-2 (IL-2), interleukine- 4 (IL-4) et l'activite de la myeloperoxydase (MPO) dans les tissus coliques ainsi que l'activite MPO dans le serum ont tons ete mesures par des methodes biochimiques et des tests ELISA sandwich. Comparativement a ce qui a ete observe chez le groupe temoin TNBS, le traitement avec les GSPE a facilite la regression des modifications pathologiques induites par le TNBS, comme demontre par une augmentation de poids (p < 0,01), une diminution de la relation poids/longueur (p < 0,01) colique et une reduction considerable des scores microscopiques et macroscopiques du colon (p < 0,01). L'activite MPO dans les tissus coliques et le serum des rats traites avec les GSPE a ete nettement plus faible que celle du groupe temoin TNBS. Les taux de MDA et d'IL-1 β dans les tissus coliques ont aussi diminue chez les groupes GSPE. L'effet antiinflammatoire intestinal des GSPE a ete accompanne d'une augmentation significative des taux d'IL-2 et d'IL-4 dans les tissus coliques des rats du groupe GSPE 400 mg/kg (p < 0,05). Comparativement an groupe SASP, les groupes GSPE n'ont pas montre de difference significative dans l'effet therapeutique (p > 0,05). Les GSPE ont un effet antiinflammatoire benefique dans la phase aigue de la colite induite par le TNBS, en diminuant un certain nombre de mediateurs impliques dans la resonse inflammatoire intestinale, en inhibant l'infiltration cellulaire inflammatoire, les dommages oxydatifs, en favorisant la reparation du tissu lese pour diminuer le stress oxydatif colique, en diminuant la production des cytokines proinflammatoires IL-1 β et en augmentant celle des cytokines antiinflammatoires IL-2 et IL-4. Mots-cles : proanthocyanidines extraites des graines de raisin, colite ulcereuse, acide trinitrobenzene sulfonique, antiinflammatoires, antioxydation, interleukine. [Traduit par la Redaction], Introduction Ulcerative colitis (UC) is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology (Cho 2001; Kankuri et al. 2003). Many factors have been implicated in [...]