• Bulletin of the Korean Chemical Society
• /
• v.8 no.1
• /
• pp.15-19
• /
• 1987

Preparation of optically pure (3R, 4R)-4-acetoxy-3-[(1R)-1-hydroxyethyl]azetidin-2-o ne derivatives, which can be employed as starting materials for synthesis of carbapenem and penem antibiotics, was established in high efficiency from 6-amino-penicillanic acid (6-APA). 6-APA was diazotized and brominated to give 6, 6-dibromopenicillanic acid and its methyl ester was metalated with methylmagnesium bromide and condensed with acetaldehyde. The product, methyl 6-bromo-6-(1-hydroxyethyl)penicillanate was reduced with Zn-$NH_4Cl-NH_4OH$-acetone efficiently to give methyl 6-(l-hydroxyethyl)-penicillanate, which was protected either with ${\beta},{\beta},{\beta}$ -trichloroethoxycarbonyl group or with t-butyldimethylsilyl group. The thiazolidine rings of these compounds were cleaved by treatment of mercury(II) acetate in acetic acid and permangante in acetone in sequence to afford the desired optically pure final products.

• Applied Chemistry for Engineering
• /
• v.7 no.6
• /
• pp.1096-1104
• /
• 1996

In order to synthesize a new antibacterial and antitumor agents, we have prepared new analogues pteroic acid(13a, 13b), which means C-9 position of pteroic acid has been replaced by norfloxacin(8) or ciprofloxacin(9) and amino group of C-2 position by $CH_3$. These derivatives were synthesized coupling at N-4 piperazine of norfloxacin and ciprofloxacin with 2-amino-3-cyano-5-chloromethylpyrazine(20) provided 1-alkyl(ethyl, cyclopropyl)-6-fluoro-1,4-dihydro-4-oxo-7-[[4-N-(2-amino-3-cyanopyrazin-5-yl)methyl]piperazin-1-yl]-3-quinoline-carboxylic acid(12a, 12b). It was then cyclized with acetamidine. HCI to obtain new analogues of C-2 desaminomethylpteroic acid(13a, 13b) in yield of 76.2% and 82.8 % respectively. These compounds were tested in vitro on antibacterial activity against Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa ATCC9027. In general, these synthesized compounds(13a, 13b) showed less potent activities than those of norfloxacin.

• YAKHAK HOEJI
• /
• v.44 no.4
• /
• pp.318-324
• /
• 2000

9 New cephalosporin derivatives were synthesized and screened for antibacterial activities against various bacteria. (6R,7R) -7$\beta$-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(fluoromethoxyimino)acetamido]-3-[(2-hydroxycarbamoyl)-s-triazolo[1,5-a]-pyrimidin-7-yl]thiomethyl]-3-cephem-4-carboxylic acid sodium salt (compound 3) showed 2 fold enhanced in vitro activity against P. aerurginosa, compared to ceftazidime.

• Archives of Pharmacal Research
• /
• v.16 no.2
• /
• pp.168-174
• /
• 1993

The michael adducts 2a, b were obtained from the reaction of the phenylacelyl derivative 1 with benzadehyde and p-anisaldehyde and p-anisaldehyde respectively. 2a and 2b were subjected to react with cyanoethanoic acid hydrazide, malononitrile, cyanothioacetamide, cyanoacetamide and 1, 1, 3-tricyano-2-amino propene to yield 4a-h and 5a, b respecitively. Hydrogen peroxide oxidation of 2a, b gave the aurone derivative 6a, b. The pyone derivatives 8a, b were obtained from 2a, b by addition of chioroacetyl chioride followed by dehydrochlorination.

• Environmental Analysis Health and Toxicology
• /
• v.4 no.3_4
• /
• pp.1-6
• /
• 1989

The effects of his ($\beta$-amino-ethyl-oxo) oxalate and bis ($\alpha$-amino-methyl-oxo) oxalate on the toxicity of lead acetate in rast were examined. Rats were given intraperitoneally at the dose of lead acetate 45 mg/kg. The exposure of lead acetate showed the 70% decrease of ALAD ($\delta$-amino levulinic acid dehydratase) activity in red blood cell. In vivo 122 mg/kg administration of bis ($\beta$-amino-ethyl-oxo) oxalate and bis ($\alpha$-amino-methyl-oxo) oxalate showed the 50% increase of ALAD activity, whereas 149 mg/kg administeration of Ca-EDTA had no effect. In vitro, the same results were obtained. Both compounds had hemolytic activity at concentrations higher than that required for showing the 50% ALAD activity increase in vivo.

• Journal of the Korean Applied Science and Technology
• /
• v.18 no.1
• /
• pp.55-59
• /
• 2001

These N-acyl amino acid surfactants is normally produced by reaction of acid anhydride with sodium ${\ell}-glutamate$ hydrolysates under Schotten-Baumann condition i.e., in alkaline aqueous medium. To avoid using fatty acid chlorides, acylations were also carried out with the fatty acids themselves or with their methyl esters, but unfortunately these methods cannot be used in practice, dodecenyl succinic anhydride, was to be studied for their suitability as acylating agents the production if acylated glutamine hydrolysates. The surface activities including surface tension forming power, forming stability and emulsifying power were measured. The experimental results revealed that the products have a good emulsifying power. Thus, there derivatives will be expected to be used an emulsifying agent for O/W type cosmetic emulsion.

• YAKHAK HOEJI
• /
• v.40 no.3
• /
• pp.279-292
• /
• 1996

To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycar bonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU${\simeq}$FUAH. The hydrolysis of N-acyloxycarboyl derivatives, greater at higher pH, was enhanced in presence of liver homogenate or human plasma. Meanwhile, acetic acid ester derivatives, very stable, were hydrolyzed by liver homogenate. Absorption rate constants were 0.181, 0.121, 0.111, 0.168, 0.168, 0.116 and 0.125 $hr^{-1}$ for 5-FU, BGFU, BLFU, CGFU, CLFU, FUAP and FUAH, respectively. The cytotoxicity of N-acyloxycarbonyl derivatives was 4 to 5 times lower than that of 5-FU, but that of acetic acid ester derivatives was negligeble. The $LD_{50}$ values were 204, 325.97 (133.59, amount as 5-FU), 708.16 (262.13), 663.50 (211.77), 382.33 (192.54) and 272.33 (130.09) mg/kg for 5-FU, BGFU, CGFU, CLFU, FUAP and FUAH, respectively. While N-acyloxycarbonyl derivatives showed enhanced antitumor activity and therapeutic ratio (3.30, 3.06, 4.19, 3.11 and 1.81 for BGFU, BLFU, CGFU, CLFU and 5-FU, respectively), FUAH and FUAP showed a smaller therapeutic ratio (0.79 and 0.83).

• YAKHAK HOEJI
• /
• v.41 no.5
• /
• pp.575-581
• /
• 1997

The 6,7-dichlorquinoline-5,8-dione was reacted with ${alpha}$-cyanoacetic acid ethyl ester in ammonia solution to yield 6-(${alpha}$-cyano-${alpha}$-ethoxycarbonyhnethyl)-7-chloroquinoline- 5,8-dione (compound I). When this compound was reacted with some alkyl amines (methylamine, ethylamine, isopropylamine, etc) 2-amino-3-ethoxycarbonyl-N-alkyl-pyridino[2,3-f]indole-4,9-diones (compounds II a-e) were obtained.

• Archives of Pharmacal Research
• /
• v.20 no.5
• /
• pp.507-509
• /
• 1997

Several new spiro compounds were synthesized via one-pot ternary condensation of isatin, malononitrile and each of thiobarbituric acid, barbituric, 3-methyl-pyrazolin-5-one, 1-phenyl-3-methyl-pyrazolin-5-one, acetylacetone, benzoylacetone, ethyl acetoacetate, phenacyl cyanide or ethyl-cyanoacetate dimer. Structures and reaction mechanisms were reported and supported via a second synthetic route.

• Journal of the Korean Chemical Society
• /
• v.34 no.3
• /
• pp.260-266
• /
• 1990

The electrochemical behavior of N-methyl-2-amino-l-cyclopentene-l-dithiocarboxylic acid $(N-CH_3 acdc) and 2-amino-l-cyclopentene-l-dithiomethyl ester (S-CH_3 acdc) in DMF have been investigated by the use of polarography, cyclic voltammetry and coulometry. The dimer of N-CH_3 acdc is further oxidized at +0.98 V via 2-electron process to produce free sulfur atom and cyclization product. The ring formation between two dithio group occurs along with the elimination of one sulfur atom. The elimination of sulfur atom occurs via two electron oxidation process at + 0.98 V vs. Ag/AgCl electrode. However, the cyclization does not occur in the S-CH_3$ acdc.