• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1003-1008
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• 2009

The $O_sO_4$-catalyzed dihydroxylations of a monosubstituted allylic amine and $\gamma-amino-\alpha,\;\beta-unsaturated$ (E)-esters with bulky alkyl groups showed a high anti-selectivity. Since the acyclic conformation of N-acyloxy protected allylic amines was efficiently controlled by a bulky t-Bu or OBO ester group, the anti diastereoselectivity of >12.5:1 was obtained without applying a chiral reagent. The synthetic utility of the present method was demonstrated by a stereoselective and efficient synthesis of an $\alpha$-glucosidase inhibitor 15 from commercially available N-Cbz-L-serine 6 in 11 steps and 31% yield.

• YAKHAK HOEJI
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• v.28 no.4
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• pp.197-206
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• 1984

The derivatives of N-(alkylcarbamoyl) amino acid methyl ester, N-(2-chloroethylcarbamoyl)-glycine methyl ester (7a), -valine methyl ester (8a), -phenylalanine methyl ester (9a), N-(N'-methylcarbamoyl)-glycine methyl ester (7b), -valine methyl ester (8b), and-phenylalanine methyl ester (9b), were prepared by reacting the corresponding free amino acid methyl ester (glycine-, valine-, phenylalanine-methyl ester) with isocyanate (R-N=C=O${\cdot};R=Cl-CH_2-CH_2-or\; CH_3-)$. The prepared N-(alkylcarbamoyl) amino acid methyl esters (7,8,9) were treated with $NaNO_2$/98% HCOOH in order to obtain their nitrosoated products, N-(alkyl-N'-nitrosocarbmoyl)amino acid methyl ester. The compound (7,8,9) gave N-(2-chloroethyl-N'-nitrosocarbamoyl)-valine methyl ester (14a),-phenylalanine methyl ester (15a), N-(N'-alkyl-N'-nitrosocarbamoyl)-glycine methyl ester (13b),-valine methyl ester. (14b), and-phenylalanine methyl ester (15b) respectively under the nitrosoation. On the other hand, N-(2-chloroethylcarbamoyl) glycine methyl ester produced N-(2-chloroethylcarbamoyl)-N-nitrosoglycine methyl ester (13a). The inhibitory activity of the prepared N-(alkylcarbamoyl) amino acid methyl ester (7,8,9) and N-(alkyl-N'-nitrosocarbamoyl) amino acid methyl ester (13,14,15) towards the growth of L1210 murine leukemia cells were examined. Among them the compound (14a) and (15a) exhibit excellent activity having $ED_{50}\; to\;be\;1.5{\mu}g/ml\;and\;3.0{\mu}g/ml respectively.

• Korean Journal of Environmental Agriculture
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• v.16 no.3
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• pp.269-273
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• 1997

This research aims at developing a new plant growth inhibitors related to abscisic acid by means of esterification of (S)-(+)-ABA with p-hydroxy methyl cinnamate and umbelliferone, and testing its biological activity on growth of rice seedlings. The over-all yield of ABA-methyl cinnamate(AC) and ABA-umbelliferone(AC) ester compounds were 83% and 78%, respectively. The growth inhibition activity of these synthetic compounds were shown about 3 to 10 times(AC) and 10 to 30 times(AU) higher than (S)-(+)-ABA.

• Bulletin of the Korean Chemical Society
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• v.19 no.6
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• pp.689-695
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• 1998

Carbobenzoxy-alanyl-thiaarginine benzyl ester and carbobenzoxy-alanyl-thialysine benzyl ester were synthesized in solution. Kinetic studies were carried out using three different analytical methods, semi-classical method, progress curve analysis and competitive spectrophotometry. In competitive spectrophotometry, carbobenzoxy-valyl-glycyl-arginyl-p-nitroaniline was used as a detector. Kinetic constants such as $K_m$ and $V_{max}$ measured by competitive spectrophotometry are almost the same as those values measured by semi-classical method. Colorimetric Ellman's assays showed the thio-peptido mimetics to be a suitable substrates for trypsin. Kinetic studies with trypsin gave $K_m$ of 2.33 mM and $k_{cat}$ of $1.50{\times}10^5\;min^{-1}$ for carboxy-alanyl-thiaarginine benzyl ester and $K_m$ of $3.41{\times}10^{-3}\; Mm\; and\; k_{cat}\; of\; 520{\times}102\; min^{-1}$ for carbobenzoxy-alanyl-thialysine benzyl ester, respectively. Kinetic constants $(K_m=2.04{\times}10^{-2}\; mM, K_{cat}=4.42{\times}10^3 \;min^{-1})$ for natural substrate, carbobenzoxy-alanyl-lysine benzyl ester, were also evaluated by competitive spectrophotometry in order to compare the mode of binding on trypsin.

• Korean Journal of Microbiology
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• v.33 no.3
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• pp.181-186
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• 1997

Sugar ester compounds were synthesized in organic solvent using lipase. Anhydrous pyridinc was selected as ;I solvent because of reasonable solubility of sugar. The synthesis of sugar ester compound was catalyzed by Pseudomonas sp. lipase in the reaction system containing anhydrous pyridine as .i solvent and vinyl butylate as an acyl donor. The analysis of the reaction product by TLC and GC showed thilt monobutyryl and dibutyryl fructose esters were synthesized by transesterification reaction between fructose and vinyl butyrate. Optimal conditions for the transesterification reaction were as follows: the ratio of fructoselvinyl butylate, I : lO(M : M): reaction temperature, 40^{\circ}C.$, velocity of shaking, 150 rprn: concentration of enzyme, 10 mglml. The longer the reaction period, the higher the conversion rate, and the conversion rate reached up to 90% after about 10 days of reaction. Monobutyryl fructose was mainly synthesized in the early stage of reaction, but the amount of dibutyryl fructose increased gradually as the rcdction progressed. When a small amount of water was added to the reaction mixture (micro-water system), the reaction rate decreased, while that of rnonobutyr~l fructosc increased. Only monobutyryl fructose was obtained when 1% water was added to the reaction mixture.

• Journal of the Korean Chemical Society
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• v.47 no.4
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• pp.427-431
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• 2003

• Journal of Pharmaceutical Investigation
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• v.18 no.3
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• pp.139-144
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• 1988

Piperacillin phthalidyl ester was synthesized by reacting piperacillin with triethylamine and bromophthalide in acetone and its chemical structure was determined by UV, IR, and PMR. The partition coefficient of the ester was increased and the ester was more lipophilic and less water soluble than piperacillin. The ester did not show the antimicrobial activity against Bacillus subtilis ATCC 6633 in vitro, but when hydrolyzed, the parent drug of ester, piperacillin, revealed antimicrobial activity in vivo. After a single oral dose of both piperacillin and the ester to rabbits, the serum piperacillin concentration was measured by bioassay. The ester exhibited improved pharmatokinetic characteristics: $T_{max}\;of\;2hr,\;C_{max}\;of\;4.26{\mu}g{\cdot}ml^{-1},K_{el}\;of\;0.057hr^{-1},\;and\;total\;AUC\;of\;85.42{\mu}g{\cdot}hr{\cdot}ml^{-1}$. Piperacillin on the other hand, did not exhibit any gastro-intestinal absorption.

• Journal of Life Science
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• v.14 no.1
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• pp.91-97
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• 2004

As a part of our study on the improvement of anticonvulsant, here we report the synthesis of N-acyl-$\alpha$-aminosuc-cinimides 1 and N-acyl-$\alpha$-aminoglutarimides 2. (R)-Benzoic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylester 6a, (R)-4-nifro-benzoic acid 4-benzyloxycarbonylamino-2- oxo-pyrrolidin-1-yl ester 6b, (R) -4-nitro-benzoic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl ester 6c, and (R)-propionic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl ester 6d were synthesized from (R)-2-benzyloxy carbonylamino-succinic acid 3 as a starting meterial. (R)-(3- Benzyloxycarbonylamino-2,6-dioxo-piperidin-1-yloxy)-acetic acid methyl ester 10a, (R)-(3-benzyloxycarbonylamino-2,6-dioxo-piperidin-1-yloxy)-acetic acid ethy1 ester 10b, an d (R)-2-(3-benzyloxycarbonylamino-2,6- diox o-piperidin-1-yl oxy)-propionic acid methyl ester l0c were synthesized from (R)- 3-carbobenzyloxy-amino-glutarmic acid 7 as a starting meterial. The yield, mp, IR, $^1H-NMR,\; and^{13}C$- NMR spectra of the products 6a, 6b, 6c, 6d, 10a, l0b, l0c are summarized in footnote. The biological studies of these compounds are in progress and will be reported in future.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.139-148
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• 1992

A prodrug of cefazolin pivaloyloxymethyl ester (CFZ-PV) was synthesized to improve oral absorption and bioavailability of parent drug by esterification of sodium cefazolin (CFZ) with chloromethyl pivalate. The successful synthesis of CFZ-PV was confirmed by spectroscopic analysis. Partition coefficient studies showed that CFZ-PV is more lipophilic than CFZ. The pharmacokinetic characteristics of CFZ-PV and CFZ preparations were compared following oral administrations of these compounds to rabbits. The analysis of CFZ in plasma was conducted by HPLC method. The ester compound (prod rug) was not detected in plasma following oral administration of CFZ-PV, and although CFZ-PV had not microbiological activity in vitro, the plasma taken after CFZ-PV administration had microbiological activity. From above observations, it was noted that CFZ-PV is rapidly hydrolyzed to CFZ in the body. And it was found that the oral absorption of CFZ-PV was increased, yielding 2-fold higher bioavailability than CFZ. From the results of this experiment, it was concluded that CFZ-PV could be a novel prodrug of CFZ which can improve the oral bioavailability of CFZ.

• Journal of Pharmaceutical Investigation
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• v.24 no.4
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• pp.265-271
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• 1994

Cefazolin ethoxycarbonylethyl ester (CFZ-ET) was synthesized to improve oral absorption and bioavailability of the parent drug by esterification of sodium cefazolin (CFZ-Na). The successful synthesis of CFZ-ET was identified with analysis of UV spectra, FT-lR spectra and NMR spectra. Partition coefficient studies showed that CFZ-ET was more lipophilic than CFZ-Na and the ester was hydrolyzed into the parent drug in vivo. Although CFZ-ET did not have antimicrobial activity in vitro, the plasma taken after the oral administration of CFZ-ET had antimicrobial activity. Based on above observations, CFZ-ET might be rapidly hydrolyzed to CFZ in the body. Therefore, it may be concluded that CFZ-ET could be a novel prodrug of CFZ which can improve the bioavailability of CFZ-Na.