Synthesis of substituted styrenes and 3-vinylphenols using ruthenium-catalyzed ring-closing enyne metathesis.

The synthesis of substituted styrenes 3 and 3-vinylphenols 9 was achieved by ring-closing enyne metathesis (RCEM)/dehydration of 7 and RCEM/tautomerization of 8, respectively. Those methods provide selective access to unique aromatic compounds and solve the problem of regioisomer formation.

Asymmetric α-amination reaction of alkenyl trifluoroacetates catalyzed by a chiral phosphine-silver complex.

The asymmetric α-amination of alkenyl trifluoroacetates with dialkyl azodicarboxylates catalyzed by the DTBM-SEGPHOS·AgOTf complex takes place in the presence of 2,2,2-trifluoroethanol with almost quantitative yield and high ees of up to 97%.

Enantioselective protonation of alkenyl trifluoroacetates catalyzed by chiral tin methoxide.

Go catalytic! A catalytic enantioselective protonation of alkenyl trifluoroacetates was achieved by using an in situ generated chiral tin bromide methoxide as the chiral catalyst in the presence of methanol. Optically active ketones containing a tertiary stereogenic center at the α-position were obtained with enantioselectivities of up to 94 % ee.

Development of asymmetric reactions catalyzed by chiral organotin-alkoxide reagents.

Asymmetric catalysis under almost-neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)-BINOL-derived chiral tin-dibromide reagent that possesses a bulky aryl group at the 3 or 3' position as the chiral pre-catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three-component Mannich-type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N-nitroso aldol reaction of unsaturated lactones with nitrosoarenes.

Synthesis of 4-vinylindoles using ruthenium-catalyzed ring-closing enyne metathesis.

The selective synthesis of substituted 4-vinylindoles by the ring-closing enyne metathesis (RCEM)/dehydration sequence is reported. In contrast with many known methods in which a pyrrole ring is constructed onto a functionalized benzene precursor, this method enables the construction of a benzene ring onto a pyrrole precursor. The RCEM/tautomerization sequence for the synthesis of 7-hydroxy-4-vinylindole is also presented as an application of this method.

Rigid P-chiral phosphine ligands with tert-butylmethylphosphino groups for rhodium-catalyzed asymmetric hydrogenation of functionalized alkenes.

Both enantiomers of 2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*), 1,2-bis(tert-butylmethylphosphino)benzene (BenzP*), and 1,2-bis(tert-butylmethylphosphino)-4,5-(methylenedioxy)benzene (DioxyBenzP*) were prepared in short steps from enantiopure (S)- and (R)-tert-butylmethylphosphine-boranes as the key intermediates. All of these ligands were crystalline solids and were not readily oxidized on exposure to air. Their rhodium complexes exhibited excellent enantioselectivities and high catalytic activities in the asymmetric hydrogenation of functionalized alkenes, such as dehydroamino acid derivatives and enamides. The practical utility of these catalysts was demonstrated by the efficient preparation of several chiral pharmaceutical ingredients having an amino acid or a secondary amine component. A rhodium complex of the structurally simple ligand BenzP* was used for the mechanistic study of asymmetric hydrogenation. Low-temperature NMR studies together with DFT calculations using methyl α-acetamidocinnamate as the standard model substrate revealed new aspects of the reaction pathways and the enantioselection mechanism.

Synthesis of biaryl compounds using tandem ruthenium-catalyzed ring-closing metathesis.

Tandem ring-closing enyne metathesis (RCEM)/ring-closing olefin metathesis (RCM) of tetraenynes with Grubbs second-generation catalyst, followed by elimination, was found to be a new and efficient synthetic approach to biaryl compounds. A preliminary asymmetric version of this approach, which used homochiral Ru-alkylidene catalysts, is also presented.

Enantioselective nitroso aldol reaction catalyzed by QuinoxP*.silver(I) complex and tin methoxide.

A catalytic enantioselective O-nitroso aldol reaction of alkenyl trichloroacetates with nitrosoarenes was achieved using the (R,R)-t-Bu-QuinoxP*.AgOAc complex as the chiral catalyst and Bu(2)Sn(OMe)(2) as the achiral cocatalyst in the presence of methanol. Optically active alpha-aminooxy ketones with up to 99% ee were regioselectively obtained in high yields from various alkenyl trichloroacetates of cyclic ketones.

Rapid screening for asymmetric catalysts: the efficient connection of two different catalytic asymmetric reactions.

A screening method for asymmetric catalysts is reported in which a metal-containing optically-active product of an asymmetric reaction is employed as a chiral catalyst in another asymmetric reaction; the rapid preparation and instant testing system of catalysts resulted in a considerable reduction in the time required for the screening process.

Synthesis of carbocyclic aromatic compounds using ruthenium-catalyzed ring-closing enyne metathesis.

General synthetic methods of substituted carbocyclic aromatic compounds are reported. Ring-closing enyne metathesis (RCEM)/dehydration of 1,5-octadien-7-yn-4-ols 6 and RCEM/tautomerization of 1,5-octadien-7-yn-4-ones 7 furnished a wide variety of substituted styrenes 4 and 4-vinylphenols 8, respectively. Acyclic precursors 6 and 7 were readily prepared from beta-halo-alpha,beta-unsaturated aldehydes 9 or 3-halo-2-propene-1-ols 13 by utilizing combinations of the Sonogashira coupling, allylation, and the Dess-Martin oxidation. The RCEM/dehydration for the synthesis of 1,3,5-tris(1-phenylethenyl)benzene derivative 4r and the RCEM/RCM/dehydration for the synthesis of 1,1'-binaphthyl derivative 19a are also presented as applications of this method.

[Optimization of dark-blood T2-weighted sequence in myocardium magnetic resonance imaging].

The evaluation of myocardium characterization is an important role in cardiac MRI. The dark-blood (DB) sequence is used for non-enhanced T2-weighted myocardial images. The purpose of this study was to evaluate and optimize the DB T2WI sequence in myocardium images. We changed the parameters TE, echo train length (ETL), inversion time (TI), and fat suppression method, respectively. Data acquisition with end-diastolic phase was effective for avoiding the blur that was caused by cardiac motion. Consequently, the optimal setting of ETL and TI was important for myocardial images. STIR was suitable for fat suppression in unstable susceptibility. Setting the parameters synchronized with the cardiac cycle provided optimal myocardial images in DB T2WI.

Recent advances in chiral phosphine-silver(I) complex-catalyzed asymmetric reactions.

Since the first report of silver(I)-catalyzed asymmetric aldol-type reaction of activated isocyanides with aldehydes using a chiral ferrocenylphosphine as a chiral phosphine ligand has been appeared in 1990, various chiral phosphine-silver(I) catalysts have been utilized in asymmetric transformations. This feature articles describes recent examples of chiral phosphine-silver(I) complex-catalyzed asymmetric reactions such as allylation, aldol reaction, Mannich-type reaction, hetero-Diels-Alder reaction, 1,3-dipolar cycloaddition and nitroso aldol reaction.

Asymmetric syn-selective Henry reaction catalyzed by the sulfonyldiamine-CuCl-pyridine system.

A catalytic asymmetric Henry reaction has been developed with use of a sulfonyldiamine-CuCl complex as a catalyst. A series of new binaphthyl-containing sulfonyldiamine ligands (2a-h) were readily synthesized in two steps starting from commercially available chiral 1,2-diamines. The (R,R)-diamine-(R)-binaphthyl ligand (2d)-CuCl complex smoothly catalyzed the enantioselective Henry reaction with the assistance of pyridine to give the corresponding adduct with high enantiomeric excess (up to 93%). Moreover, the 2d-CuCl-pyridine system promotes the diastereoselective Henry reaction in syn-selective manner to give the adduct in up to 99% yield with 92:8 syn/ anti selectivity. The enantiomeric excess of the syn-adduct was 84% ee.

Practical asymmetric Henry reaction catalyzed by a chiral diamine-Cu(OAc)2 complex.

The chiral diamine ligand 3 was designed and synthesized from (R,R)-1,2-diphenylethylenediamine, (S)-2,2'-dibromomethyl-1,1'-binaphthalene, and o-xylylene dibromide. The resulting 3-Cu(OAc)2 complex was a highly efficient catalyst for the Henry reaction, giving the various nitroaldols with over 90% ee (up to >99%). The reaction was performed in n-propyl alcohol at room temperature, and the Henry adducts were produced in high yield with excellent enantiomeric excess; these attributes are desirable in a catalyst for practical use.

Reaction optimization using solid-phase catalysis-CD HTS: Nb-imidazoline-Cu(I)-catalyzed asymmetric benzoylation of 1,2-diols.

Catalytic asymmetric benzoylation of 1,2-diols has been developed using a solid-phase asymmetric catalyst. The reaction conditions were optimized by the screening of different metal salts, solvents, bases, and temperatures. High-throughput screening was performed using circular dichroism detection, and the results revealed that Nb-imidazoline-copper(I) in combination with diisopropylethylamine was able to catalyze with high enantioselectivity, giving the monobenzoylated products in high yields and excellent enantiomeric excesses of up to 95% ee. [reaction: see text]

Systemic inflammatory response syndrome after hand-assisted laparoscopic distal pancreatectomy.

BACKGROUND: Although the clinical benefits of hand-assisted laparoscopic surgery have been shown in several procedures including colorectal resection, splenectomy and gastrectomy, efficacy and invasiveness in pancreatic surgery have not been well investigated. We assessed the clinical benefits and invasiveness of hand-assisted laparoscopic distal pancreatectomy (HALS-DP) in relation to the occurrence of post-operative systemic inflammatory response syndrome (SIRS). METHODS: Subjects comprised 8 patients underwent HALS-DP (with splenectomy, n = 7; without splenectomy, n = 1) for benign or low malignant pancreatic lesions between March 2004 and December 2005. Indications for HALS-DP consisted of mucinous cystadenoma (n = 4), endocrine tumors (n = 2), serous cystadenoma (n = 1) and pancreatic pseudocyst (n = 1). Controls comprised 9 patients who underwent conventional open distal pancreatectomy (Open-DP) for benign or low malignant lesions of the pancreas in the same period. RESULTS: No significant differences were identified between HALS-DP and Open-DP in operation time. However, intra-operative blood loss, CRP on post-operative day (POD) 1 [5.5 mg/dl (1.8-8.1) vs. 9.7 mg/dl (5.9-12.1); p = .006] and POD 3 [8.5 mg/dl (1.7-11.1) vs. 17.7 mg/dl (10.7-21.5); p = .003], occurrence of post-operative SIRS (13% vs. 67%; p < .05, one-sided), duration of SIRS [0 day (0-1) vs. 1 day (0-4); p = .02] and post-operative hospital stay were significantly lower in HALS-DP than in Open-DP. Furthermore, no pancreatic fistula was seen with HALS-DP, as compared to 2 (22%) with Open-DP. CONCLUSION: HALS-DP is safer and less invasive than Open-DP for benign or low malignant pancreatic tumors.

[Usefulness of phase-sensitive inversion recovery in delayed enhanced cardiac MRI].

BACKGROUND: Delayed-enhancement MRI is a technique that has significant clinical usefulness, particularly for myocardial viability determination in ischemic heart disease. Delayed enhanced images have been acquired by using the inversion recovery(IR)method. It is necessary for the IR method to select optimal inversion time(TI). Recently, the phase-sensitive inversion recovery(PSIR)method has been developed to detect Gd-DTPA enhanced myocardium. PURPOSE: To compare the IR method with the PSIR method by acquiring Gd-DTPA solution phantoms A(0.05 mmol/l)and B(0.04 mmol/l)in various parameters. METHOD: Images were acquired using a turbo-fast low angle shot(t-flash)sequence in each method. RESULTS: The null point of signal intensity(SI)shortened as the flip angle(FA)and segments increased in the IR method. Excess segments also caused the duration of breath holding to be extended. The IR method might cause reversed SI between normal and Gd-DTPA enhanced myocardium if the optimal TI was not carefully selected. On the other hand, PSIR had no problem in obtaining phase-sensitive images that were converted into positive SI keeping inverse longitudinal magnetization. The PSIR method avoided the need to select optimal TI and loss of contrast. CONCLUSION: The PSIR method was a useful sequence for delayed-enhancement MRI to detect Gd-DTPA enhanced myocardium.

Catalytic asymmetric protonation of lithium enolates using amino acid derivatives as chiral proton sources.

[reaction: see text] Asymmetric protonation of lithium enolates was examined using commercially available amino acid derivatives as chiral proton sources. Among the amino acid derivatives tested, Nbeta-l-aspartyl-l-phenylalanine methyl ester was found to cause significant asymmetric induction in the protonation of lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained in the presence of a catalytic amount of the chiral proton source was higher than those obtained in the stoichiometric reaction.

Knife blade penetrating stab wound to the brain--case report--.

A 28-year-old man attempted to kill himself with a knife stab into the parietal area. Neuroimaging showed no vascular impairment except slow venous flow around the knife due to tamponading. After obtaining informed consent, the knife was removed through a craniotomy without new brain injury. Postoperative neurological findings showed no deficit. Follow-up angiography revealed no vascular impairment. No infection occurred. Brain stab wounds cause numerous complications, such as intracranial hemorrhage, injury of important vessels, and infections. Minimal blade movement during removal and precautions to prevent massive hemorrhage are essential.

[A pediatric case of multiple sclerosis mimicking malignant brain tumor].

We report a pediatric case of multiple sclerosis mimicking malignant brain tumor. A 11-year-old male presented with high fever, vomiting and partial convulsion of left lower extremity followed by left visual impairment. Magnetic resonance imaging (MRI) revealed a mass lesion in the right frontal lobe with significant peripheral edema. Incomplete ring-like enhancement by gadolinium administration was also noted. Open biopsy of the lesion was undertaken that provided pathological confirmation of demyelinating changes. Luxol fast blue stain and Bodian stain demonstrated extensive myelin loss and good preservation of axons. The patient was given intravenous high-dose methyl-prednisolone and sequential oral low-dose prednisone, which improved his neurological status progressively. The lesion was dramatically decreased in size and finally disappeared. Although many tumor-like demyelinating lesions were reported previously, pediatric cases of multiple sclerosis mimicking malignant brain tumor are extremely rare. Pathological examinations including Luxol fast blue stain and Bodian stain are essential for exact diagnosis.