Kyung Il Choi

Mild and Efficient Reduction of Sulfoxides to Sulfides with Titanium Tetrachloride–Indium System

Abstract TiCl4/In system was found to be a new reagent for reducing various sulfoxides to the corresponding sulfides in good yields under mild conditions.

KKHA-761, a potent D3 receptor antagonist with high 5-HT1A receptor affinity, exhibits antipsychotic properties in animal models of schizophrenia

KKHA-761, 1-{4-[3-(3,4-dimethoxy-phenyl)-isoxazol-5-yl]-butyl}-4-(2-methoxy-phenyl)-piperazine, has a high affinity (Ki=3.85 nM) for human dopamine D3 receptor with about 70-fold selectivity over the human dopamine D(2L) receptor (Ki=270 nM). KKHA-761 also showed high affinity for cloned human 5-HT1A receptor (Ki=6.4 nM). KKHA-761 exhibited D3 and 5-HT1A receptor antagonist activities in vitro, reversing dopamine- or 5-HT-mediated stimulation of [35S]GTPrS binding. The in vivo pharmacological profile of KKHA-761 was compared with both typical and atypical antipsychotics including clozapine and haloperidol. Apomorphine-induced dopaminergic behavior, cage climbing, in mice was potently blocked by a single administration (i.p.) of KKHA-761 (ID50=4.06 mg/kg) or clozapine (ID50=4.0 mg/kg). Cocaine- or MK-801-induced hyperactivity in animals was markedly inhibited by KKHA-761 or clozapine. In addition, KKHA-761 significantly reversed the disruption of prepulse inhibition (PPI) produced by apomorphine in mice, indicating the antidopaminergic or antipsychotic activity of KKHA-761 in mice. However, KKHA-761 was inactive in the forced swimming behavioral despair model in mice, suggesting lack of antidepressant properties. KKHA-761 attenuated the hypothermia induced by a selective dopamine D3 agonist, 7-OH-DPAT, in mice, whereas clozapine enhanced it. Moderate doses of both KKHA-761 and clozapine did not increase serum prolactin levels in rats. Lower doses of, however, haloperidol significantly increased prolactin secretion. KKHA-761 did not induce cataleptic response up to 20 mg/kg, but significant catalepsy was shown at lower doses of clozapine and haloperidol. Furthermore, KKHA-761 showed a low incidence of rotarod ataxia (TD50=34.4 mg/kg, i.p.) in mice. The present results, therefore, suggest that KKHA-761 is a potent antipsychotic agent with combined dopamine D3 and serotonin 5-HT1A receptors modulation activity, which may further enhance its therapeutic potential for anxiety, psychotic depression, and other related disorders.

Synthesis and in vitro activity of new oxazolidinone antibacterial agents having substituted isoxazoles.

Two series of oxazolidinone derivatives having substituted isoxazoles were synthesized and tested for antibacterial activities against several Gram-positive strains including the resistant strains of Staphylococcus and Enterococcus, such as MRSA, CRSA, MSSA and VRE. Some of them showed in vitro activities (MIC) comparable or superior to the reference compound vancomycin.

Solution-phase combinatorial synthesis of isoxazolines and isoxazoles using [2+3] cycloaddition reaction of nitrile oxides

Abstract An efficient way to construct a library of isoxazoles and isoxazolines was developed by solution-phase 1,3-dipolar cycloaddition reaction of nitrile oxides with olefins and alkynes followed by precipitation of the products as HCl salts.

Indium and zinc mediated Barbier type reactions: Allylation and propargylation reactions of 6-oxopenicillanate and 7-oxocephalosporanate

Abstract Allylation and propargylation of compounds, 6-oxopenicillanate 1 and 7-oxocephalosporanate 2 , were accomplished by reacting the corresponding bromides in the presence of indium or zinc. Both indium and zinc gave alkylated products in moderate yields under mild conditions. Indium mediated Barbier reactions in aqueous THF exhibited slightly higher stereoselectivity than zinc mediated reactions in anhydrous THF.

Indium-mediated diastereoselective allylation reactions: preparation of tert-α-hydroxy acids

Indium-mediated allylation reactions of α-ketoimides derived from Oppolzers sultam were accomplished in aqueous THF in good yields and excellent diastereomeric excesses. It could be a useful method for the preparation of enantiopure t-α-hydroxy acids. When the substituent of α-ketoimides was changed from phenyl to thiophenyl or furyl group, diastereoselectivity decreased in comparison to N-phenyl derivatives, but changing solvent to aqueous ethanol provided improved levels of diastereoselectivity.

Indium mediated allylation and propargylation reactions of dimethyl acetals and ketals

Abstract Indium mediated allylation and propargylation reactions of acetals and ketals with various allyl or propargyl bromides in aqueous media successfully provided the corresponding homoallylic or homopropargylic (and allenylic) alcohol, respectively, in moderate to good yields. Highly chemoselective allylation is also described. The ketal and aryl acetal could be selectively allylated over the aliphatic one in 80–84% yields.

3D QSAR studies on new oxazolidinone antibacterial agents by comparative molecular field analysis

Three-dimensional QSAR studies for two series of new oxazolidinone antibacterial agents were conducted using the comparative molecular field analysis (CoMFA). In vitro activities (MICs) of the compounds against methicillin-resistant Staphylococcus aureus 88 (MRSA 88) exhibited a strong correlation with their steric, electrostatic factors and lipophilicities.

Stereochemical control in diastereoselective reduction of α-substituted-β-ketoesters using a reductase purified from Kluyveromyces marxianus

An NADPH-dependent carbonyl reductase that shows (3R)-selective reducing activity for α-substituted-β-ketoesters was purified from Kluyveromyces marxianus and racemic alkyl 2-substituted-3-oxobutanoates were reduced to the corresponding (2S,3R)- or (2R,3R)-2-substituted-3-hydroxybutanoates with enantiomeric purity (> 99%) and diastereoselectivity (24 ∼ 98%).

Facile Deoxygenation of Amine‐N‐oxides With CoCl2 · 6H2O–Indium System

Abstract CoCl2 · 6H2O/In system was found to be a new reagent for deoxygenation of various amine‐N‐oxides to the corresponding amines in good to excellent yields under sonication.