RESUMO
A series of novel diphosphinoamine (PNP) ligands bearing a P-alkenyl group were synthesized and applied in chromium-catalyzed selective ethylene tri-/tetramerization by in situ combination of Cr(acac)3 and modified methylalumoxane (MMAO-3A). The ligand substitution and oligomerization conditions have a remarkable influence on the catalytic activity and controllable selectivity. Most of these PNP ligands are highly active for ethylene tri-/tetramerization with considerable selectivity. An asymmetric diisopropenylphosphanyl ligand with an N-cyclohexyl group achieved the highest activity of 2036 kg (g Cr h-1)-1 with a high total selectivity of 81.1 wt% toward valuable 1-hexene (43.0 wt%) and 1-octene (38.1 wt%) at 40 bar ethylene and 60 °C. An asymmetric mixed isopropenyl/ethylphosphanyl ligand with an N-isopropyl group exhibited a high 1-octene selectivity of 65.5 wt% and a high total 1-hexene/1-octene selectivity (91.5 wt%) with a high activity of 1256 kg (g Cr h-1)-1.
RESUMO
Axially chiral biaryl δ-amino acids possess significantly different conformational properties and chiral environment from centrally chiral amino acids, therefore, have drawn considerable attention in the fields of synthetic and medicinal chemistry. Herein, a novel chiral phenanthroline-potassium catalyst has been developed by constructing a well-organized axially chiral ligand composed of one 1,10-phenanthroline unit and two axially chiral 1,1'-bi-2-naphthol (BINOL) units. In the presence of this catalyst, good to excellent yields and enantioselectivities (up to 99 % yield, 98 : 2 er) have been achieved in the ring-opening alcoholytic dynamic kinetic resolution of a variety of biaryl lactams, thereby providing an efficient protocol for catalytic asymmetric synthesis of unnatural axially chiral biaryl δ-amino acid derivatives.
RESUMO
Organocatalyzed diastereo- and enantioselective [3 + 2] cycloaddition reactions of donor-acceptor (D-A) cyclopropanes with isatin-derived ketimines are presented. Different from well-developed Lewis acid activation protocols which promote the reactivity of D-A cyclopropanes through coordinating to the acceptor group, in this reaction, dicyanocyclopropylmethyl ketones can be activated through nucleophilic activation of the donor group by using dihydroquinine-derived squaramide as Brønsted base catalyst. The reaction affords functionalized spiro[oxindole-3,2'-pyrrolidines] with two nonadjacent tetra- and tri-substituted stereocenters in 83-99% yields, moderate to excellent diastereoselectivities (up to >20:1 diastereomeric ratio (dr)), and excellent enantioselectivities (up to >99% enantiomeric excess (ee)) under mild conditions.
RESUMO
Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1'-bi-2-naphthol (BINOL) unit which are connected via a C-O single bond. The two conformers of the catalyst induced by the rotation about the C-O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1'-binaphthyl-2,2'-diamine (BINAM) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.
Assuntos
Diaminas , Catálise , Cristalografia por Raios X , Diaminas/química , Conformação MolecularRESUMO
An efficient organocatalytic diastereo- and enantioselective formal [3 + 2] cycloaddition reaction of α-isocyanoacetates with saccharin-derived 1-azadienes catalyzed by a dihydroquinine derived squaramide catalyst has been investigated, and it furnished the corresponding directly linked benzo[d]isothiazole 1,1-dioxide-dihydropyrroles with two adjacent tertiary-quaternary stereocenters in high yields (up to 98%), with moderate to excellent stereoselectivities (up to >20 : 1 dr and 97% ee) under mild conditions.
RESUMO
A catalytic asymmetric synthesis of 3,4-dihydrocoumarins with adjacent tertiary-quaternary stereocenters by 1,6-addition/transesterification cascade reaction of α-isocyanoacetates with ortho-hydroxyphenyl-substituted para-quinone methides (p-QMs) has been developed. Using a combination of dihydroquinidine-derived aminophosphine and silver nitrate as a binary catalytic system, moderate to good yields, excellent diastereoselectivities (>20 : 1 dr) and good to excellent enantioselectivities (up to 94% ee) were achieved for a wide range of isocyanoacetates and p-QMs.
RESUMO
We reported herein an unexpected cinchona alkaloid-derived squaramide-catalyzed asymmetric two-component Ugi-type reaction of α-aryl-substituted isocyanoacetates with C,N-cyclic azomethine imines, which provides concise access to optically active C1-oxazole-substituted tetrahydroisoquinolines in good yields (86-93%) and high enantioselectivities (up to 98% enantiomeric excess) under mild conditions.
Assuntos
Alcaloides de Cinchona/química , Oxazóis/química , Quinina/análogos & derivados , Tetra-Hidroisoquinolinas/síntese química , Acetatos/química , Compostos Azo/química , Catálise , Iminas/química , Isocianatos/química , Estrutura Molecular , Quinina/química , Tetra-Hidroisoquinolinas/química , Tiossemicarbazonas/químicaRESUMO
In the era of rituximab, the International Prognostic Index (IPI) has been inefficient in initial risk stratification for patients with R-CHOP-treated diffuse large B-cell lymphoma (DLBCL). To estimate the predictive values of PET/CT quantitative parameters and three prognostic models consisting of baseline and interim parameters for three-year progression-free survival (PFS), we conducted an analysis of 85 patients in China with DLBCL underwent baseline and interim PET/CT scans and treated at the Department of Hematology of Peking University Third Hospital from November 2012 to November 2017. The PET/CT parameters, viz. the baseline and interim values of standardized uptake value (SUVmax ), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), and their rates of change, were analyzed by a receiver operating characteristics curve, Kaplan-Meier analysis, and log-rank test. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was also included in the multivariate Cox hazards model. Owing to the strong correlation between TMTV and TLG at baseline and interim (Pearson's correlation coefficient, r = 0.823, P-value = 0.000, and 0.988, P-value = 0.000, respectively), only TLG was included in the multivariate Cox hazards model, where TLG0 > 1036.61 g and %ΔSUVmax < 86.02% showed predictive value independently (HR = 10.42, 95% CI 2.35-46.30, P = 0.002, and HR = 4.86, 95% CI 1.27-18.54, P = 0.021, respectively). Replacing TLG in the equation, TMTV0 and TMTV1 both showed significantly predictive abilities like TLG (HR = 8.22, 95% CI 1.86-32.24, P = 0.005, and HR = 2.96, 95% CI 1.16-7.54, P = 0.023, respectively). After dichotomy, NCCN-IPI also gave a significant performance (P = 0.035 and P = 0.010, respectively, in TLG and TMTV models). The baseline variables, that is, TMTV0 , TLG0 and dichotomized NCCN-IPI, and the interim variables TMTV1 and %ΔSUVmax , presented independent prognostic value for PFS. In prognostic model 2 (TLG0 + %ΔSUVmax ), the group with TLG0 > 1036.61 g and %ΔSUVmax < 86.02% recognized 19 (82.6%) of the relapse or progression events, which showed the best screening ability among three models consisting of baseline and interim PET/CT parameters.
Assuntos
Biomarcadores , Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso de 80 Anos ou mais , Criança , Feminino , Glicólise , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Carga Tumoral , Adulto JovemRESUMO
An efficient organocatalytic asymmetric tandem conjugate addition-protonation of α-substituted isocyanoacetates to 2-chloroacrylonitrile catalyzed by dihydroquinine-derived thiourea has been investigated, affording the corresponding adducts with two non-adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) along with good to excellent diastereo- and enantioselectivities (up to 20 : 1 dr, up to 95% ee) under mild conditions. The adduct can also be transformed into chiral γ-lactam by synthetic transformations.
RESUMO
We have developed an efficient diastereo- and enantioselective Mannich/cyclization cascade reaction of α-substituted isocyanoacetates with 4-aryl-3-carbonyl-1,2,5-thiadiazole-1,1-dioxide type cyclic sulfamide ketimines cooperatively catalyzed by cinchona alkaloid-derived squaramide and AgOAc. The corresponding optically active 2,3,3a,4-tetrahydroimidazo[1,5-b][1,2,5]thiadiazole-1,1-dioxide derivatives were obtained in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >20 : 1 dr, up to 94% ee).
RESUMO
Cinchona alkaloid squaramide can effectively catalyze the asymmetric Michael addition of α-aryl isocyanoacetates to ß-trifluoromethylated enones, affording the corresponding adducts with an adjacent chiral tertiary carbon center bearing a CF3 group and a quaternary carbon center in moderate to good yields along with excellent stereoselectivities. The adduct can be easily transformed into biologically attractive chiral ß-trifluoromethylated pyrroline carboxylate in high yield via an isocyano group hydrolysis/cyclization/dehydration cascade reaction by treating with acid. The one-pot enantioselective Michael addition/isocyano group hydrolysis/cyclization/dehydration sequential protocol has also been investigated.
RESUMO
An efficient diastereo- and enantioselective Mannich-type/cyclization cascade reaction of α-substituted isocyanoacetates and cyclic trifluoromethyl ketimines cooperatively catalyzed by cinchona alkaloid-derived multi-hydrogen-bonding donor squaramide and AgOAc has been investigated, affording the optically active trifluoromethyl-substituted tetrahydroimidazo[1,5-c]quinazoline derivatives in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >15:1 dr, up to 98% ee) under mild conditions.
Assuntos
Acetatos/química , Alcaloides de Cinchona/química , Compostos Heterocíclicos/síntese química , Iminas/química , Nitrilas/química , Catálise , Ciclização , Compostos Heterocíclicos/química , Estrutura Molecular , EstereoisomerismoRESUMO
An efficient enantioselective hydrazination/cyclization cascade reaction of α-substituted isocyanoacetates to azodicarboxylates catalyzed by Cinchona alkaloid derived squaramide catalysts has been investigated, affording the optically active 1,2,4-triazolines in excellent yields (up to 99%) and good to excellent enantioselectivities (up to 97% ee) under mild conditions.
Assuntos
Acetatos/química , Amidas/química , Alcaloides de Cinchona/química , Ácidos Dicarboxílicos/química , Triazóis/síntese química , Compostos Azo/química , Catálise , Ciclização , Isocianatos/química , Estrutura Molecular , Estereoisomerismo , Triazóis/químicaRESUMO
Axially chiral oxazoline-carbene ligands with an N-naphthyl framework were successfully prepared, and their coordination behavior with AuCl·SMe(2) was also investigated, affording the corresponding Au(I) complexes in moderate to high yields.
RESUMO
It is better to be cooperative: A highly diastereo- and enantioselective asymmetric [3+2] cycloaddition reaction of α-aryl isocyanoacetates with N-aryl maleimides through cooperative catalysis of cinchona alkaloid-derived squaramide/AgSbF(6) was developed. A wide range of optically active, substituted 1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c] pyrrole derivatives was obtained in high yields (up to 98%), high diastereoselectivities (>20:1 d.r.), and good to excellent enantioselectivities (up to 92% ee) under mild reaction conditions.
RESUMO
A highly enantioselective Michael addition of 3-aryloxindole to vinyl bisphosphonate ester catalyzed by a cinchonidine derived thiourea catalyst has been investigated. The corresponding adducts, containing a chiral quaternary carbon center and geminal bisphosphonate ester fragment at the 3-position of the oxindole, were obtained in moderate to good yields (65-92%) and moderate to good enantioselectivities (up to 92% ee).
Assuntos
Alcaloides de Cinchona/química , Difosfonatos/química , Ésteres/química , Indóis/química , Tioureia/química , Catálise , Estrutura Molecular , Oxindóis , EstereoisomerismoRESUMO
OBJECTIVE: To analyze the expressions of TrkB and TRIM29 in biopsy tissues from preoperative gastroscopy in patients with gastric cancer and investigate the relationship between their expression and rate of lymph node metastasis. METHODS: Through immunohistochemistry, the authors analyzed the expression status of TRIM29 and TrkB in biopsy tissues from preoperative gastroscopy in 67 patients with a diagnosis of gastric cancer undergoing radical operations during 2005 - 2009 at Peking University Third Hospital. There were 39 males and 28 females. Then the relationship was explored between the expression of both proteins and lymph node metastasis and other clinical pathological factors. Image pro Plus 6.0 software was used for image analysis. The data underwent a logarithmic process and were analyzed through SPSS 17.0 statistical software. RESULTS: The expression of TrkB in lymph node metastasis (n = 42) was higher than that in without lymph node metastasis (n = 25) (lgA 4.79 ± 0.42 vs 3.98 ± 0.71, t = -5.873, P = 0.003), while the expression of TRIM29 with lymph node metastasis (n = 36) was also higher than that in without lymph node metastasis (n = 24) (5.21 ± 0.27 vs 5.02 ± 0.37, t = -2.257, P = 0.040). Logistic regression analysis showed that the TrkB expression was an independent predictor for lymph node metastasis. A discriminant was set based on the result (discriminant value = 1.705 × TrkB lgA+ 1.803 × TRIM29 lgA-16.880, cutoff value = 0). This discriminant achieved a prediction accuracy of 80.0% (48/60), a positive likelihood ratio 3.332 and a negative likelihood ratio 0.223. Patients with a high expression of TrkB showed a worse survival rate than those with a low TrkB expression [36.0% (9/25) vs 66.7% (16/24), P = 0.047). Patients with a high TRIM 29 expression showed a worse survival rate than those with a low TRIM29 expression [38.1% (8/21) vs 66.7% (14/21), P = 0.044]. CONCLUSION: The expressions of TrkB and TRIM29 are correlated with lymph node metastasis in gastric cancer, and discriminant based on the expressions of TrkB and TRIM29 had important values for preoperative prediction of lymph node metastasis in gastric cancer.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Mucosa Gástrica/patologia , Metástase Linfática/patologia , Receptor trkB/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo , Adulto , Idoso , Biópsia/métodos , Feminino , Mucosa Gástrica/metabolismo , Gastroscopia , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismoRESUMO
Palladium complexes with an axially chiral N-Ar framework have been developed. These complexes showed high stereoselectivities in asymmetric allylic arylation to achieve the kinetic resolution of Morita-Baylis-Hillman adducts, affording up to 99% ee of (E)-allylation products and 92% ee of recovered Morita-Baylis-Hillman adducts.
RESUMO
Axially chiral mono(NHC)-Pd(II) and mono(NHC)-Au(I) complexes with one side shaped 1,1'-biphenyl backbone have been prepared from chiral 6,6'-dimethoxybiphenyl-2,2'-diamine. The complexes were characterized by X-ray crystal structure diffraction. The Pd(II) complex showed good catalytic activities in the Suzuki-Miyaura and Heck-Mizoroki coupling reactions, and the (S)-Au(I) complexes also showed good catalytic activities in the asymmetric intramolecular hydroamination reaction to give the corresponding product in moderate ee.