Electroreductive coupling of 2-acylbenzoates with α,ß-unsaturated carbonyl compounds: density functional theory study on product selectivity.

The electroreductive coupling of 2-acylbenzoates with acrylonitrile in the presence of TMSCl and successive treatment with 1 M HCl gave 2-cyanonaphthalen-1-ols or 3-(3-cyanoethyl)phthalides. On the other hand, the reaction of 2-acylbenzoates with methyl vinyl ketone under the same conditions produced 3-(3-oxobutyl)phthalides as the sole products. What determines the product selectivity was studied using DFT calculations.

Hybrid Assistive Limb improves restricted hip extension after total hip arthroplasty.

The Hybrid Assistive Limb (HAL) was developed as an exoskeleton robot that supports gait training. The purpose of this study was to assess the usefulness of training using the HAL after total hip arthroplasty (THA). We targeted 16 consecutive patients who underwent THA via the posterior approach. We randomized patients to the HAL group (8 hips), in which the HAL was used as part of physical therapy, or the control group (8 hips), in which only typical physical therapy was performed. Gait analysis was performed before and after surgery, and comparisons were made between the two groups. We evaluated the single support time (%), double support time (%), cadence (steps/min), velocity (cm/s), stride length (cm), and anteroposterior and lateral variability, and assessed the hip and knee joint range of motion in the sagittal plane. The results showed improvements in the hip extension angle and other gait parameters in the HAL group. Among gait-related problems after THA, a decreased peak hip extension angle is reported to be a significant factor that affects gait disability. This study revealed that HAL usage after THA seems to be a useful method to obtain sufficient extension angle.

Electroreductive Coupling of Phthalimides with α,ß-Unsaturated Carbonyl Compounds and Subsequent Acid-Catalyzed Rearrangement to 4-Aminonaphthalen-1-ols: Density Functional Theory Study of the Acid-Catalyzed Rearrangement of Ketene Silyl Acetals.

The electroreductive coupling of phthalimides with α,ß-unsaturated carbonyl compounds in the presence of TMSCl and successive treatment of the electrochemically coupled products with TFA gave two types of rearranged products, 3- and 2-substituted 4-aminonaphthalen-1-ols. The substituent (R) on the nitrogen atom of phthalimides determined which type of 4-aminonaphthalen-1-ol was preferentially formed. Bulky and less bulky N substituents selectively afforded 3- and 2-substituted 4-aminonaphthalen-1-ols, respectively. It was presumed by the density functional theory calculations for the acid-catalyzed rearrangement of silyl ketene acetals produced by the electroreductive coupling that the rearranged product selectivity depends on whether O or N protonation of the amide group of the silyl ketene acetals occurs more rapidly.

Inchworm-type PNA-PEG conjugate regulates gene expression based on single nucleotide recognition.

In order to detect single nucleotide mutations and suppress gene expression, we synthesized an artificial nucleic acid, an inchworm-type PNA-PEG conjugate (i-PPc), that possessed a chemical structure in which 8 residues of peptide nucleic acid (PNA) were linked to both ends of a polyethylene glycol molecule. I-PPc_T7FM, which forms a complementary strand with the T7 promoter region of luciferase-expressing mRNA, failed to suppress the amount of luciferase produced via gene expression. However, 10 µM of i-PPc_ATGFM, targeting the start codon of luciferase (Luc+), suppressed approximately 85% of Luc+ production compared to that of the control in the cell-free protein synthesis system. Moreover, i-PPc_ATGMM (i-PPc_ATGFM with a single base mutation) only suppressed the amount of luciferase produced by approximately 15%, and such suppression of luciferase expression has not been achieved with block-type PPc or PNA oligos. The thermodynamic parameters suggested that the difference in stability of each PNA segment of the i-PPc contributed to single nucleotide recognition. These results indicate that the i-PPc could be used in antisense therapy to target single nucleotide polymorphisms (SNP).

Femoral Neck Fracture in a Hemodialysis Patient after Liver Transplantation: A Case Report.

BACKGROUND: Surgical treatment of femoral neck fractures is usually performed as an urgent procedure so that restoration of the ability to stand and walk can be achieved as quickly as possible. However, orthopedic surgeons need to be aware of undertreated or untreated diseases in their patients. Organ transplant recipients require immunosuppressive agents and steroids postoperatively. Hemodialysis patients also exhibit immunological deterioration and are included among immunocompromised patients. We report a case in which conservative treatment was chosen for a hepatic transplant recipient on hemodialysis who suffered a femoral neck fracture because signs of inflammation of unknown etiology were intermittently seen. CASE: The patient was a 70-year-old man who had undergone liver transplantation from a living donor as treatment for hepatocellular cancer and hepatic failure with cirrhosis. Dialysis for end-stage renal failure was initiated at approximately 1 year postoperatively. Cyclosporine was administered as an immunosuppressive agent. The patient subsequently fell off a bicycle and was unable to walk because of right hip pain. He was brought to our hospital by ambulance, and a right hip radiograph revealed a femoral neck fracture. His white blood cell count and C-reactive protein levels were intermittently elevated with unknown etiology. Conservative treatment was finally adopted, although a bipolar hip arthroplasty was planned. At 5 months after the injury, the patient was able to walk alone in a stable manner using a pair of crutches and was discharged. DISCUSSION: Conservative treatment for a femoral neck fracture, which generally requires surgery, may be acceptable in organ transplant recipients on hemodialysis.

Electroreductive Coupling of Phthalic Anhydrides with α,ß-Unsaturated Carbonyl Compounds: Synthesis of 1,4-Dihydroxynaphthalenes.

Electroreductive coupling of phthalic anhydrides with α,ß-unsaturated carbonyl compounds in the presence of TMSCl and subsequent treatment with 1 M HCl gave 1,4-dihydroxynaphthalenes and 2-methyl-2,3-dihydronaphthalene-1,4-diones.

Electroreductive Intermolecular Coupling of 4-Quinolones with Benzophenones: Synthesis of 2-Substituted 4-Quinolones.

The electroreductive coupling of 1-alkoxycarbonyl-4-quinolones with benzophenones in the presence of trimethylsilyl chloride gave adducts reacted at the 2-position of 4-quinolones as trimethylsilyl ethers. The adducts were transformed to 2-(diarylhydroxymethyl)-4-quinolones. The electroreduction of 1,3-diethoxycarbonyl-4-quinolones and polyhalogenated 3-alkoxycarbonyl-1-alkyl-4-quinolones with benzophenones also gave adducts reacted at the 2-position of 4-quinolones. On the contrary, the electroreductive coupling of 1,3-diethooxycarbonyl-8-methoxy-4-quinolones occurred at the 4-position of 4-quinolones to give 4-substituted quinolines.

Electroreductive Intermolecular Coupling of Coumarins with Benzophenones: Synthesis of 4-(2-Hydroxyphenyl)-5,5-diaryl-γ-butyrolactones, 2-(2,2-Diaryl-2,3-dihydrobenzofuran-3-yl)acetic Acids, and 4-(Diarylmethyl)coumarins.

The electroreductive coupling of coumarins with benzophenones in the presence of TMSCl gave adducts reacted at the 4-position of coumarins as trimethylsilyl ethers. From 3-methylcoumarin, 3,4-cis-adducts were formed stereoselectively. The de-trimethylsilylation of the adducts with 1 M HCl aq or TBAF in THF at 25 °C produced 4-(2-hydroxyphenyl)-5,5-diaryl-γ-butyrolactones. The γ-butyrolactones were further transformed to 2-(2,2-diaryl-2,3-dihydrobenzofuran-3-yl)acetic acids by treatment with 1 M HCl aq at reflux temperature. The de-trimethylsilylation of the adducts with 1 M HCl in MeOH afforded 2-(2,2-diaryl-2,3-dihydrobenzofuran-3-yl)acetic acid methyl esters. The de-trimethylsiloxylation of the adducts or dehydration of the γ-butyrolactones brought about 4-(diarylmethyl)coumarins.

Electroreductive Intermolecular Coupling of Uracils with Aromatic Ketones: Synthesis of 6-Substituted and cis-5,6-Disubstituted 5,6-Dihydro-1,3-dimethyluracils and Their Transformation to 6-Substituted 1,3-Dimethyluracils, trans-5,6-Disubstituted 5,6-Dihydro-1,3-dimethyluracils, and 4,5,5-Trisubstituted 3-Methyloxazolizin-2-ones.

The electroreductive coupling of 1,3-dimethyluracil, thymine, and 5-fluorouracil with aromatic ketones in the presence of TMSCl gave 6-substituted and cis-5,6-disubstituted 5,6-dihydro-1,3-dimethyluracils. The dehydrotrimethylsiloxylation of the adducts afforded 6-substituted and 5,6-fused 1,3-dimethyluracils. The detrimethylsilylation of the adducts with TBAF or 1 M HCl-MeOH gave 4,5,5-trisubstituted 3-methyloxazolizin-2-ones or 3-methyloxazolizin-2-imines in addition to simply desilylated alcohols. The cis-5,6-disubstituted 5,6-dihydro-1,3-dimethyluracils were isomerized to the corresponding trans-isomers by heating in the presence of cat. DMAP. The cis- and trans-5,6-disubstituted 5,6-dihydro-1,3-dimethyluracils were assigned by the coupling constants J5,6 of their (1)H NMR spectra.

Intermolecular reductive coupling of esters with benzophenones by low-valent titanium: synthesis of diarylmethyl ketones revisited.

The reductive coupling of aliphatic esters with benzophenones by Zn-TiCl4 in THF gave two- and four-electron reduced products, diaryl(hydroxy)methyl ketones, and diarylmethyl ketones selectively by controlling the reaction conditions. In the reaction of aromatic esters with benzophenones, diarylmethyl ketones were obtained as the sole products. N-(Alkoxycarbonyl)-(S)-α-amino acid methyl esters gave optically active diphenylmethyl ketones by reduction with benzophenone. The obtained diphenylmethyl ketones were transformed to 4,5-cis-disubstituted oxazolidin-2-ones stereoselectively.

Electroreductive coupling of optically active α,ß-unsaturated carbonyl compounds with diaryl ketones: asymmetric synthesis of 4,5,5-trisubstituted γ-butyrolactones.

The electroreductive coupling of optically active N-E-crotonoyl- and N-cinnamoylimidazolidin-2-ones and oxazolidin-2-ones with diaryl ketones in the presence of chlorotrimethylsilane gave adducts with high diastereoselectivity. The adducts were readily transformed to optically active 4,5,5-trisubstituted γ-butyrolactones by treatment with TBAF.

Reductive coupling of phthalimides with ketones and aldehydes by low-valent titanium: one-pot synthesis of alkylideneisoindolin-1-ones.

The reductive coupling of phthalimides with ketones and aldehydes by Zn-TiCl4 in THF gave two- and four-electron reduced products, 3-hydroxy-3-(1-hydroxyalkyl)isoindolin-1-ones and alkylideneisoindolin-1-ones, selectively by controlling the reaction conditions. Therefore, the one-pot synthesis of alkylideneisoindolin-1-ones from phthalimides was effected by this reaction. Although the alkylideneisoindolin-1-ones prepared from phthalimides and aldehydes were formed as mixtures of geometric isomers in most cases, the geometric ratios could be increased by reflux in cat. PPTS/toluene. After the isomerization, the E-isomers of N-methyl substituted alkylideneisoindolin-1-ones (X = Me, R(1) = R, R(2) = H) and the Z-isomers of N-unsubstituted alkylideneisoindolin-1-ones (X = H, R(1) = H, R(2) = R) were obtained preferentially.

Electroreductive intermolecular coupling of 3-methoxycarbonylindoles with ketones.

The electroreductive coupling of 1-alkoxycarbonyl-3-methoxycarbonylindoles with aromatic ketones in the presence of chlorotrimethylsilane gave cis-adducts stereoselectively. The cis-adducts were readily transformed to trans-adducts by treatment with catalyst DBU. On the other hand, the electroreductive coupling of 1-methyl-3-methoxycarbonylindole with aliphatic ketones in isopropanol afforded trans-adducts exclusively. The adducts are the precursors for the synthesis of 2-substituted 3-methoxycarbonylindoles and indolines.

Electroreductive intramolecular coupling of phthalimides with aromatic aldehydes: application to the synthesis of lennoxamine.

The electroreductive intramolecular coupling of phthalimides with aromatic aldehydes in the presence of chlorotrimethylsilane and triethylamine led to five-, six-, and seven-membered cyclized products (58-84%). The electroreductive cyclization was applied to the total synthesis of lennoxamine.

Evaluation of Aß fibrillization inhibitory effect by a PEG-peptide conjugate based on an Aß peptide fragment with intramolecular FRET.

A PEG-peptide conjugate based on an amyloid ß peptide fragment was synthesized. The formed amyloid protofibril-like aggregates induced intramolecular FRET. It proved to be useful as a bioprobe to evaluate the inhibitory effect of organic molecules toward amyloid fibrillization.

Electroreductive coupling of phthalimides with alpha,beta-unsaturated esters: unusual rearrangement of resulting silyl ketene acetals.

The electroreductive intramolecular coupling of phthalimides with alpha,beta-unsaturated esters in the presence of chlorotrimethylsilane and subsequent desilylation of resulting silyl ketene acetals with TBAF gave five- and six-membered trans-cyclized products stereospecifically. The silyl ketene acetals were readily rearranged to benzoindole and tetrahydrobenzoquinoline by standing or treatment with a Lewis acid under open-air conditions. The electroreductive intermolecular coupling of N-methylphthalimide with methyl acrylate also proceeded.

Electroreductive intramolecular coupling of 1-indolealkanones.

The electroreduction of 1-indolealkanones in isopropanol gave five-, six-, and seven-membered trans-cyclized products stereospecifically. On the other hand, the electroreduction of 3-methoxycarbonyl-1-indolealkanones afforded mixtures of two diastereomers of the corresponding trans- and cis-cyclized products. The DFT calculations for the radical anions support that the reductive couplings of 1-indolealkanones and 3-methoxycarbonyl-1-indolealkanones proceed through different reaction mechanisms.

Density functional theory study of electroreductive hydrocoupling of alpha,beta-unsaturated carbonyl compounds.

[reaction: see text] The electroreductive hydrocoupling of methyl cinnamate, methyl crotonate, cumarin, and benzalacetone was studied by DFT (B3LYP/6-311++ G**) calculations. The computational outcomes for the transition states in the hydrocoupling of anion radicals generated by a one-electron transfer to the alpha,beta-unsaturated carbonyl compounds well agree with the diastereoselectivities in the experimental results previously reported.

Electroreductive intramolecular coupling of aromatic imino esters: is four-membered cyclization much more favorable than six-membered cyclization?

[reaction: see text] The electroreduction of an aromatic imino ester prepared from (S)-glutamic acid in the presence of chlorotrimethylsilane and triethylamine afforded a four-membered cyclized product, a mixed ketal of cis-2,4-disubstituted azetidine-3-one, stereospecifically. Calculations for the transition states by the DFT method support the predominant formation of the azetidine. The electroreduction of an aromatic imino ester prepared from (S)-aspartic acid gave almost equal amounts of a diastereomerically pure mixed ketal of cis-2,4-disubstituted azetidine-3-one and a diastereomeric mixture of 2,5-disubstituted pyrollidine-3-one.

Electroreductive acylation of aromatic ketones with acylimidazoles.

[Reaction: see text]. The intermolecular reductive coupling of aromatic ketones with acylimidazoles was effected by electroreduction in the presence of chlorotrimethylsilane and gave alpha-trimethylsiloxy ketones and esters. The best result was obtained using Bu4NPF6 as a supporting electrolyte and a Pb cathode in THF. The alpha-trimethylsiloxy-containing products were transformed to the corresponding alpha-hydroxy ketones and esters by treatment with TBAF in THF. This method was also effective for the intramolecular reductive coupling of delta- and epsilon-keto acylimidazoles.