Atroposelective Total Syntheses of Naphthylisoquinoline Alkaloids with (P)-Configuration.

Asymmetric total syntheses of naphthylisoquinoline alkaloids with a (P)-configuration are described. An atroposelective Suzuki-Miyaura reaction between naphthyl pinacol boronate and an aryl iodide bearing an (S)-2-(N-acetylamino)propyl group at the ortho-position using Pd(OAc)2 in the presence of SPhos and Ba(OH)2 provided the (P)-selective biaryl product as the major product without any external chiral sources. This biaryl product was converted into naphthylisoquinoline alkaloids with a (P)-configuration via stereoselective construction of the isoquinoline framework with the appropriate oxidation state and stereochemistry.

Synthesis of Optically Pure 3,3'-Disubstituted-1,1'-Bi-6-Methoxy-2-Phenol (BIPhOL) Derivatives via Diastereomeric Resolution.

A new protocol for the enantioselective synthesis of 3,3'-disubstituted-1,1'-bi-6-methoxy-2-phenol (BIPhOL) derivatives is described. Diastereomeric resolution of racemic BIPhOL boronic acid using a boronic acid moiety as a resolving group generated two diastereomers and subsequent Suzuki-Miyaura coupling reaction of the resulting diastereomers with aryl halides provided BIPhOL derivatives without any loss of enantioselectivity. In addition, the absolute stereochemistry of chiral BIPhOL was determined by comparison of the optical rotation with the reported value.

Enantioselective Synthesis of ß-Arylamines via Chiral Phosphoric Acid-Catalyzed Asymmetric Reductive Amination.

A new method for the synthesis of chiral ß-aryl amines via chiral phosphoric acid-catalyzed enantioselective reductive amination of benzyl methyl ketone derivatives with Hantzsch ester was developed. Various chiral ß-aryl amines were obtained in high yields and with good to high enantioselectivities. This transformation is applicable to gram-scale reactions, and the catalyst loading can be reduced to 1 mol % without sacrificing any catalytic efficacy. Furthermore, the resulting ß-aryl amine was successfully converted into a tetrahydroisoquinoline compound without any loss of enantioselectivity.

Metal-free protodeboronation of electron-rich arene boronic acids and its application to ortho-functionalization of electron-rich arenes using a boronic acid as a blocking group.

The metal-free thermal protodeboronation of various electron-rich arene boronic acids was studied. Several reaction parameters controlling this protodeboronation, such as solvent, temperature, and a proton source, have been investigated. On the basis of these studies, suitable reaction conditions for protodeboronation of several types of electron-rich arene boronic acids were provided. On the basis of this protodeboronation, a new protocol for the synthesis of ortho-functionalized electron-rich arenes from these boronic acids was developed using the boronic acid moiety as a blocking group in the electrophilic aromatic substitution reaction, followed by the removal of the boronic acid moiety via thermal protodeboronation. Mechanistic studies suggested that this protodeboronation might proceed via the complex formation of a boronic acid with a proton source, followed by the carbon-boron bond fission through σ-bond metathesis, to afford the corresponding arene compound and boric acid.

Diastereomeric resolution of rac-1,1'-bi-2-naphthol boronic acid with a chiral boron ligand and its application to simultaneous synthesis of (R)- and (S)-3,3'-disubstituted 1,1'-bi-2-naphthol derivatives.

A new concept of diastereomeric resolution has been developed where a boronic acid functionality was employed as (1) a diastereomeric resolving group with a chiral boron ligand and (2) a masked functional group for further transformation thereafter. This new diastereomeric resolution method was successfully applied to the preparation of both (R)- and (S)-3,3'-disubstituted 1,1'-bi-2-naphthol (BINOL) derivatives in a step-ecomonical manner. Racemic BINOL boronic acid reacted with a commercially available pinene-derived iminodiacetic acid as a chiral boron ligand to generate the two diastereomers in quantitative yields over a gram-scale quantity. After the removal of the chiral boron ligand from the diastereomers under mild conditions, the subsequent Suzuki coupling reaction of the resulting chiral BINOL boronic acids with aryl halides provided a series of both (R)- and (S)-BINOL derivatives in good yields. Further, both resulting diastereomers could be directly applied to the Suzuki coupling reaction without the removal of the chiral ligand.

Protodeboronation of ortho- and para-phenol boronic acids and application to ortho and meta functionalization of phenols using boronic acids as blocking and directing groups.

The first metal-free thermal protodeboronation of ortho- and para-phenol boronic acids in DMSO was developed. The protodeboronation was successfully applied to the synthesis of ortho- and meta-functionalized phenols using the boronic acid moiety as a blocking group and a directing group, respectively. Mechanistic studies suggested that this protodeboronation proceeds through the coordination of water to the boron atom followed by σ-bond metathesis.

Asymmetric Total Syntheses of Naphthylisoquinoline Alkaloids via Atroposelective Coupling Reaction Using Central Chirality as Atroposelectivity-Controlling Group.

We describe the asymmetric total syntheses of naphthylisoquinoline alkaloids. Atroposelective biaryl coupling reaction between naphthyl pinacol boronate and an aryl iodide, bearing (S)-2-aminopropyl group at the ortho-position using the existing central chirality as an atroposelectivity-controlling group, provided the desired biaryl product with high atroposelectivity, without the use of an external chiral source. From the resulting biaryl product, several naphthylisoquinoline alkaloids were prepared via the stereoselective formation of the isoquinoline framework with the appropriate oxidation state and stereochemistry.

[Development and Effect of a Fall Prevention Program Based on the King's Goal Attainment Theory for Fall High-Risk Elderly Patients in Long-Term Care Hospital].

PURPOSE: The purpose of this study to develop a fringed fall prevention program based on King's goal attainment theory and education. This study is applied to the personal, interpersonal, and social systems of fall high-risk patients to test its effects. METHODS: This study was a nonequivalent control group pre- and post-test design. There were 52 fall high-risk patients in the experimental group and 45 in the control group. The experimental group received six sessions, with the group sessions lasting 60 minutes and the individual sessions lasting 20~30 minutes. Data were analyzed using descriptive statistics, an χ²-test, a paired sample t-test, and a Wilcoxon signed-ranks test utilizing IBM SPSS software. RESULTS: For the 3-month intervention period, the fall prevention program was found to be particularly effective for patients in the experimental group (from 3.38 to 1.69 per 1000 patient days; p=.044), as opposed to the control group (from 1.94 to 1.49 per 1000 patient days; p=.300). For the 6-month follow up period, the fall prevention program was again found to be effective for patients in the experimental group (from 3.26 to 0.76 per 1000 patient days; p=.049) compared to the control group (from 1.98 to 1.01 per 1000 patient days; p=.368). CONCLUSION: These results indicate that the fringed fall prevention program is very effective in reducing falls, not only during the intervention period, but also after the intervention period has ended. We can therefore recommend this program for use concerning fall high-risk patients in long-term care hospitals.