Catalytic asymmetric hydrogenations of prochiral unsaturated compounds, 1 olefin, 2 ketone, 3 and imine, 4 have been intensively studied and are considered as a versatile method of creating a chiral carbon center. 5 However, no highly enantioselective hydrogenation of heteroaromatic groups has so far been reported except that of 2-methylquinoxaline to our knowledge. 6 Resonance stability of heteroaromatic compounds might impede the enantioselective hydrogenation, 7 which may find potentially wide applicability in stereoselective organic synthesis. 8,9 Herein, we describe the highly enantioselective hydrogenation of heteroaromatic compounds, indoles.We recently disclosed that the rhodium complex generated from Rh(acac)(cod) and PPh 3 is a good catalyst for the hydrogenation of five-membered heteroaromatic compounds. 10 Thus chiral rhodium complexes prepared in situ from Rh(acac)(cod) and various commercially available chiral bisphosphines (1 mol %) were examined for asymmetric hydrogenation of N-acetyl-2-butylindole (1a) at 60°C for 2 h with 5.0 MPa of H 2 in 2-propanol (eq 1), resulting in non-enantioselective hydrogenation (0-1% ee). 11 Fortunately, the successful asymmetric hydrogenation has been achieved by use of a trans-chelating chiral bisphosphine ligand, (S,S)-(R,R)-PhTRAP, 12,13 giving (R)-N-acetyl-2-butylindoline (2a) with 85% ee (77% conversion). No reduction of the fused aromatic ring of 1a was observed.On further investigation into the asymmetric hydrogenation, [Rh(nbd) 2 ]SbF 6 was found to be superior to Rh(acac)(cod) as catalyst precursor (Table 1). It is noted that addition of base is necessary for achievement of high enantioselectivity as well as high catalytic activity. The [Rh(nbd) 2 ]SbF 6 -(S,S)-(R,R)-PhTRAP catalyst scarcely promoted the hydrogenation in the absence of base, giving a trace of 2a with only 7% ee (S) (entry 1). Addition of 10 mol % of Et 3 N or Cs 2 CO 3 brought remarkable improvement of the enantioselectivity and catalytic activity (100% conversion, 94% ee (R)) (entries 2 and 3). 14 Both the enantioselectivity and catalytic activity were significantly dependent upon base: K 2 -CO 3 gave (R)-2a with 76% ee, and pyridine did not activate the cationic PhTRAP-rhodium complex at all (entries 4 and 5). The amount of Cs 2 CO 3 did not affect the selectivity: 20 mol %, 94% ee; 1 mol %, 93% ee. It is possible to carry out the asymmetric hydrogenation at lower pressure (1.0 MPa) without significant decrease of the selectivity and reaction rate (entry 6). The amount of PhTRAP-rhodium complex can be reduced to 0.1 mol %, and the reaction was completed within 20 h to give (R)-2a of 93% ee in 92% isolated yield (entry 7).Although 2-propanol has frequently been used as a hydrogen source in the transfer hydrogenation of unsaturated compounds (1) For reviews, see: (a) Takaya, H.; Ohta, T.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH Publishers: New York
Purpose To clarify the relative frequency of various histopathological primary spinal cord tumors and their features in Japanese people and to compare this data with other reports. Methods Primary spinal cord tumor surgical cases from 2000 to 2009, which were registered in our affiliated hospital database were collected. We examined age at surgery, sex, anatomical location, vertebral level of the tumor, and pathological diagnosis in each case.Results Of the 678 patients in our study, 377 patients (55.6 %) were males and 301 patients (44.4 %) were females (male/female ratio 1.25). The mean age at surgery was 52.4 years. Of these tumors, 123 cases (18.1 %) were intramedullary, 371 cases (54.7 %) were intradural extramedullary, 28 cases (4.1 %) were epidural, and 155 cases (22.9 %) were dumbbell tumors. The pathological diagnoses included 388 schwannomas (57.2 %), 79 meningiomas (11.6 %), 54 ependymomas (8.0 %), 27 hemangiomas (4.0 %), 23 hemangioblastomas (3.4 %), 23 neurofibromas (3.4 %), and 9 astrocytomas (1.3 %). The male/female ratios for schwannomas, meningiomas, ependymomas,Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan e-mail: imagama@med.nagoya-u.ac.jp K. Sato Department of Orthopaedic Surgery, Nagoya Daini Red Cross Hospital, 2-9, Myoken-cho, Showa-ku, Nagoya 466-8650, Japan (2012( ) 21:2019( -2026( DOI 10.1007( /s00586-012-2345 hemangiomas, hemangioblastomas, neurofibromas, malignant lymphomas, and lipomas are 1.4, 0.34, 1.3, 1.5, 2.3, 1.3, 2.7 and 2.3, respectively. Conclusion This is the first published research in English on the epidemiology of primary spinal cord tumors in Japanese people. Similar to other reports from Asian countries, our data indicates a higher male/female ratio overall for spinal cord tumors, a higher proportion of nerve sheath cell tumors, and a lower proportion of meningiomas and neuroepithelial tumors compared to reports from non-Asian countries. Data in the current study represent the characteristics of primary spinal cord tumors in Asian countries.
BackgroundThe aim of this study was to elucidate the correlation between angiographic coronary vasomotor responses to intracoronary acetylcholine (ACh) injection, clinical features, and long‐term prognosis in patients with vasospastic angina (VSA).Methods and ResultsThis is a retrospective, observational, single‐center study of 1877 consecutive patients who underwent ACh‐provocation test between January 1991 and December 2010. ACh‐provoked coronary spasm was observed in 873 of 1637 patients included in the present analysis. ACh‐positive patients were more likely to be older male smokers with dyslipidemia, to have a family history of ischemic heart disease, and to have a comorbidity of coronary epicardial stenosis than were ACh‐negative patients. ACh‐positive patients were divided into 2 groups: those with focal (total or subtotal obstruction, n=511) and those with diffuse (severe diffuse vasoconstriction, n=362) spasm patterns. Multivariable logistic regression analysis identified female sex and low comorbidity of coronary epicardial stenosis to correlate with the ACh‐provoked diffuse spasm pattern in patients with VSA. Kaplan–Meier survival curve indicated better 5‐year survival rates free from major adverse cardiovascular events in patients with diffuse spasm pattern compared with those with focal spasm pattern (P=0.019). Multivariable Cox hazard regression analysis identified diffuse spasm pattern as a negative predictor of major adverse cardiovascular events in patients with VSA.ConclusionsACh‐induced diffuse coronary spasm was frequently observed in female VSA patients free of severe coronary epicardial stenosis and was associated with better prognosis than focal spasm. These results suggest the need to identify the ACh‐provoked coronary spasm subtypes in patients with VSA.
Tenomodulin (TeM) is a type II transmembrane glycoprotein that contains a C-terminal domain with homology to the mature, secreted form of chondromodulin-I (ChM-I), a cartilage-derived angiogenesis inhibitor. TeM transcripts have been found in hypovascular tissues such as tendons and ligaments but the biological activity of TeM has not yet been fully explored. Using an adenovirus expression system, we utilized the forced expression and subsequent secretion of the human TeM C-terminal 116 amino acids (Ad-shTeM) in human umbilical vein endothelial cells (HUVECs) to assess the anti-angiogenic properties of TeM. The C-terminal 120 amino acids of the human ChM-I precursor (Ad-shChM-I) was similarly expressed in HUVECs as a comparison study. Transduction of both Ad-shTeM and Ad-shChM-I resulted in significant impairment of the tube-forming activity of HUVECs, when cultured in Matrigel. Similarly, conditioned medium from COS7 cells, transfected with plasmid DNA encoding shTeM or shChM-I, inhibited tube formation of HUVECs when compared to medium derived from either COS7 cells transfected with control vector or from non-transfected cells. Upon infection of HUVECs with Ad-shTeM or Ad-shChM-I, DNA synthesis stimulated by vascular endothelial growth factor (VEGF) was reduced to 40-50% of normal levels. Additionally, in a modified Boyden chamber assay, migration of HUVECs in response to VEGF was significantly affected following transduction of either Ad-shTeM or Ad-shChM-I and these transduced HUVECs were found to spread well on type I collagen or fibronectin, but not on vitronectin. Furthermore, the transduction of either Ad-shTeM or Ad-shChM-I in human melanoma cells resulted in suppression of tumor growth in association with decreased vessel density in vivo. Hence, we have demonstrated that, similarly to ChM-1, the C-terminal domain of TeM exhibits both anti-angiogenic and anti-tumor activities when expressed in a secreted form.
The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.