• Journal of the Korean Chemical Society
• /
• v.43 no.3
• /
• pp.294-301
• /
• 1999

Geminal bisphosphonates have been well known to be effective inhibitors of various calciumrelated disorders such as Paget's disease, hypercalcemia of malignancy, and osteoporosis. To synthesize bisphosphonates, we have used the pentacovalent oxaphospholene prepared from methyl vinyl ketone and triethyl-phosphite. Υ-Ketobisphosphonates are obtained by bromination, applied Westheimer reaction, and hydrolysis of synthesized oxaphospholene. This compound was converted to the N-alkylated Υ-aminobisphosphonates by the reductive amination. Conversion of the resulting secondary amine to the tertiary one, followed by introduction of the second alkyl group on the nitrogen, was led to the synthesis of new N,N'-dialkylated Υ-aminobisphosphonates.

• Bulletin of the Korean Chemical Society
• /
• v.16 no.5
• /
• pp.416-421
• /
• 1995

The approximate rates and stoichiometry of the reaction of excess lithium gallium hydride with selected organic compounds containing representative functional groups were examined under the standard conditions (diethyl ether, 0 $^{\circ}C)$ in order to compare its reducing characteristics with lithium aluminum hydride and lithium borohydride previously reported, and enlarge the scope of its applicability as a reducing agent. Alcohols, phenol, and amines evolve hydrogen rapidly and quantitatively. However lithium gallium hydride reacts with only one active hydrogen of primary amine. Aldehydes and ketones of diverse structure are rapidly reduced to the corresponding alcohols. Conjugated aldehyde and ketone such as cinnamaldehyde and methyl vinyl ketone are rapidly reduced to the corresponding saturated alcohols. p-Benzoquinone is mainly reduces to hydroquinone. Caproic acid and benzoic acid liberate hydrogen rapidly and quantitatively, but reduction proceeds slowly. The acid chlorides and esters tested are all rapidly reduced to the corresponding alcohols. Alkyl halides and epoxides are reduced rapidly with an uptake of 1 equiv of hydride. Styrene oxide is reduced to give 1-phenylethanol quantitatively. Primary amides are reduced slowly. Benzonitrile consumes 2.0 equiv of hydride rapidly, whereas capronitrile is reduced slowly. Nitro compounds consumed 2.9 equiv of hydride, of which 1.9 equiv is for reduction, whereas azobenzene, and azoxybenzene are inert toward this reagent. Cyclohexanone oxime is reduced consuming 2.0 equiv of hydride for reduction at a moderate rate. Pyridine is inert toward this reagent. Disulfides and sulfoxides are reduced slowly, whereas sulfide, sulfone, and sulfonate are inert under these reaction conditions. Sulfonic acid evolves 1 equiv of hydrogen instantly, but reduction is not proceeded.

• Bulletin of the Korean Chemical Society
• /
• v.25 no.4
• /
• pp.533-538
• /
• 2004

Canonical sampling method has been presented to generate the initial conditions for reactive flux studies of organic reactions in water. Velocity Verlet version of Nose-Hoover chain dynamics algorithm has been employed to sample the initial conditions according to canonical distribution. The unstable normal mode of a transition state has been introduced to define a dividing plane separating reactant and product regions in reaction processes. This method has been implemented and tested for the case iels-Alder reaction of methyl vinyl ketone (MVK) and cyclopentadiene (CPD) in water, providing a reliable tool for further reactive flux molecular dynamics studies in condensed media.

• Bulletin of the Korean Chemical Society
• /
• v.12 no.5
• /
• pp.483-487
• /
• 1991

The tetraaza macrocyclic ligand 3,14-dimethyl-2,6,13,17-tetraazatricyclo $[14,4,0^{1.18} ,0^{7.12}]$docosa-2,12-diene(B), that contains two cyclohexane rings, has been prepared as its dihydroperchlorate salt by the nontemplate condensation of methyl vinyl ketone with 1,2-diaminocyclohexane and perchloric acid. Reduction of B with sodium borohydride produces 3,14-dimethyl-2,6,13,17-tetraazatricyclo$[14,4,0^{1.18},0^{7.12}]$docosane(C). Square planar Ni(Ⅱ) and Cu(Ⅱ) complexes of B and C have been prepared by the reaction of the metal ions and the ligands. Synthesis, characterization, and the properties of the ligands and their metal complexes are reported.

• Bulletin of the Korean Chemical Society
• /
• v.23 no.9
• /
• pp.1218-1242
• /
• 2002

Photochemical reactions of aromatic carbonyl compounds with silyl ketene acetals have been explored. Irradiation of acetonitrile or benzene solutions containing aryl aldehydes or ketones in the presence of silyl ketene acetals is observed to promo te formation of ${\beta}-hydroxyester$, 2,2-dioxyoxetane and 3,3-dioxyoxetane products. The ratios of these photoproducts, which arise by competitive single electron transfer (SET) and classical Paterno-Buchi mechanistic pathways, is found to be dependent on the degree of methyl-substitution on the vinyl moieties of the ketene acetals in a manner which reflects expected alkyl substituent effects on the oxidation potentials of these electron rich donors. An analysis of the product distribution arising by irradiation of a solution containing butyrophenone (6) and the silyl ketene acetal 9, derived from methyl isobutyrate, provides an estimate of the rate constants for the competitive Norrish type Ⅱ, SET and Paterno-Buchi processes occuring. Finally, sequences involving silyl ketene acetal-aryl aldehyde or ketone photoaddition followed by 2,2-dioxyoxetane hydrolysis represent useful procedures for Claisen-condensation type, ${\beta}-hydroxyester$ synthesis.

• Archives of Pharmacal Research
• /
• v.20 no.3
• /
• pp.253-258
• /
• 1997

Ten, heretofore unreported, $ 5^I-methyl-5^I-[2-(5-substituted uracil-1-yl)ethyl)]-2^I-oxo-3^I$-methylenetetrahydrofurans (H, F, Cl, Br, I, $ CH_3$,$CF_3$,$CH_2CH_3$,$ CH=CH2$, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of ${\alpha}$-methylene-${\gamma}$-butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl ${\alpha}$-(bromomethyl)acrylate and zinc with the respective 1-(5-substituted uracil-1-yl)-3-butanone (6a-j). The 5-substituted uracil ketones (6a-j) were directly obtained by the respective Michael type reaction of vinyl methyl ketone with the $K_2CO_3$(or NaH)-treated 5-substituted uracils (5a-j) in the presence of acetic acid in the DMF solvent. The .alpha.-methylene-.gamma.-butyrolactone compounds showing the most significant antitumor activity are 7e, 7f, 7h and 7j (inhibitory concentration $(IC_50)$ ranging from 0.69 to $2.9 {\mu}g/ml$), while 7b, 7g and 7i have shown moderate to significant activity. The compounds 7a, 7c and 7d were found to be inactive. The synthetic intermediate compounds 6a-j were also screened and found marginal to moderate activity where compounds 6b and 6g showed significant activity $(IC_50:0.4~2.8 {\mu}g/ml)$.

• Toxicological Research
• /
• v.30 no.3
• /
• pp.149-157
• /
• 2014

Smoking is one of the most serious but preventable causes of cardiovascular disease (CVD). Key aspects of pathological process associated with smoking include endothelial dysfunction, a prothrombotic state, inflammation, altered lipid metabolism, and hypoxia. Multiple molecular events are involved in smoking-induced CVD. However, the dysregulations of reactive oxygen species (ROS) generation and metabolism mainly contribute to the development of diverse CVDs, and NADPH oxidase (NOX) has been established as a source of ROS responsible for the pathogenesis of CVD. NOX activation and resultant ROS production by cigarette smoke (CS) treatment have been widely observed in isolated blood vessels and cultured vascular cells, including endothelial and smooth muscle cells. NOX-mediated oxidative stress has also been demonstrated in animal studies. Of the various NOX isoforms, NOX2 has been reported to mediate ROS generation by CS, but other isoforms were not tested thoroughly. Of the many CS constituents, nicotine, methyl vinyl ketone, and ${\alpha}$,${\beta}$-unsaturated aldehydes, such as, acrolein and crotonaldehyde, appear to be primarily responsible for NOX-mediated cytotoxicity, but additional validation will be needed. Human epidemiological studies have reported relationships between polymorphisms in the CYBA gene encoding p22phox, a catalytic subunit of NOX and susceptibility to smoking-related CVDs. In particular, G allele carriers of A640G and $-930^{A/G}$ polymorphisms were found to be vulnerable to smoking-induced cardiovascular toxicity, but results for C242T studies are conflicting. On the whole, evidence implicates the etiological role of NOX in smoking-induced CVD, but the clinical relevance of NOX activation by smoking and its contribution to CVD require further validation in human studies. A detailed understanding of the role of NOX would be helpful to assess the risk of smoking to human health, to define high-risk subgroups, and to develop strategies to prevent or treat smoking-induced CVD.