(${\pm}$)-cis-8-Amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno [1,2-b][1,4]oxazine의 합성

마은숙,Ma, Eun-Sook 대한약학회 2008 약학회지 Vol.52 No.6

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine D3 agonist with low neurotoxicity. Dopamine D3 agonist was evaluated as selective for the treatment of Parkinson's disease. In order to develop a novel dopamine D3 agonist, we tried to synthesize the aminothiazoloindenoxazine derivative that is a hybrid structure of aminoindenoxazine and thiazole ring. cis-2-Amino-1-indanol (2) was synthesized from 1,2-indandione-2-oxime by catalytic hydrogenation and it was treated with chloroacetyl chloride and NaH in benzene solution to give (${\pm}$)-cis-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one (6). Nitration of 6 by the mixed acid gave 8-nitro compound (7) and the carbonyl group of 7 was reduced with $LiAlH_4$ to afford compound (8). 8 was reduced to form (${\pm}$)-cis-8-amino-2,3,4,4a,5,9b-hexahydroindeno[1,2-b][1,4]oxazine (9) and finally it was cyclized with KSCN in glacial acetic acid to yield (${\pm}$)-cis-8-amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine (10).

9,10- 디플루오르 -5,6,6a,7,11b- 펜타하이드로인다노[2,1-c] 이소퀴놀린의 합성

마은숙,김민정,Ma, Eun-Sook,Kim, Min-Jung 대한약학회 2000 약학회지 Vol.44 No.6

The synthesis of pentahydroindanoisoquinoline (4) compound has been achieved via the cyclization of 2-(N-benzylamino)-5,6-difluoro-1-indanol (10a, 10b), which was prepared by condensation and reduction of 2-amino-1-indanol and benzaldehyde in ethanol. The stereochemistry of $H_{6a}$ and $H_{11b}$ of 9,10-difluoro-5,6,6a,7,11b-pentahydroindano[2,1-c]isoquinoline (4) was the trans B/C ring fusion.

MS-5, a Naphthalene Derivative, Induces the Apoptosis of an Ovarian Cancer Cell CAOV-3 by Interfering with the Reactive Oxygen Species Generation

마은숙,정선주,최준석,Thi Ha Nguyen,정철호,주상훈 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1

Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS (H2O2), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.

5,6-디플루오르 -2-아미노인단.염산염의 합성

마은숙 대한약학회 1999 약학회지 Vol.43 No.6

3,4-Difluoroamphetamine.HCI and 5,6-difluoro-2-aminoindan.HCI were synthesized as serotonergic agents. 3,4-Difluorobenzaldehyde was condensed with nitroethane and reduced with $LiAlH_4$ to obtain 3,4-difluoroamphetamine. And 5,6-difluoro-2-aminoidan.HCI was synthesizd through reactions of condensation with malonic acid, 10% Pd-C reduction, cyclization with polyphosphoric acid, oximation and catalytic hydrogenation.

2-置換 Benzimidazole 誘導體에 관한 硏究(I)

馬銀淑 대구효성가톨릭대학교 1986 연구논문집 Vol.33 No.1

In order to investigate the difference of IR and NMR spectra according to substituent group, six 2-substituted benzimidazole derivatives such as 2-ethyl-2-(α-hydroxyethyl)-, 2-acetyl-, 2-benzyl-,2-(α-hydroxybenzyl)-, 2-benzyl BI were synthesized by Phillips method. In the IR spectra, the differences of IR spectra according to substituent group were not found except common properities of benzimidazole compound. In the NMR spectra, as was the substituent group of 2-position changed ?????????????? AA′BB′proton of benzimidazole ring was downfield shift and when benzene was substituted instead of methyl group, the effect of downfield shift was more large.

2-置換 Benzimidazole 誘導體에 관한 硏究(Ⅱ)

馬銀淑 대구효성가톨릭대학교 1987 연구논문집 Vol.34 No.1

According to Phillips method, seven 2-substituted benzimidazole derivatives such as n-propyl BI, 2-benzimidazolepropionic acid, 1,2-bis-(2-benzimidazolyl)ethane, 2-benzimidazole-α,β-dihydroxypropionic acid, 1,2-bis-(2-benzimidazolyl)-1.2-ethandiol, 1,2-bis-(2-benzimidazolyl) ethanol and sulfate salt were synthesized and investigated difference of mono compound and bis compound in IR and MNR spectra. The difference of IR spectra was especially not found according to substituent group and not seen between mono compound and bis compound. In NMR spectra, since the environment of π-electron density of connecting unit was same, the chemical shift of conneting unit(-CH-CH-, CH₂-CH₂-) had singlet peak in bis compound, but mono compound had multiplet peaks. And as was connecting unit changed -CH-CH- → CH₂-CH₂- → -CH-CH₂-, AA'BB' | | | OH OH OH porton of BI ring was became downfield shift.

1,2-Di-O-benzyl-6, 7-O-isopropylidene-1,2,6,7-tetrahydroxy-hept-3-ene의 합성(Ⅰ)

마은숙 대구효성가톨릭대학교 응용과학연구소 1994 응용과학연구논문집 Vol.3 No.-

1,2-Di-O-benzyl-6,7-O-isopropylidene-1,2,6,7-tetrahydroxy-hept-3-ene(10) was prepared as intermediate of β-hydroxy-δ-lactone moiety in compactin. Compactin is not only potent inhibitor of enzyme HMG-CoA reductase(HMGR), the rate-limiting enzyme in cholesterol biosynthesis, but also effective hypocholestereolemic agents in man. 3,4-O-Isopropylidene-3,4-dihydroxybut-1-yl triphenyl phosphonium iodide(4) was synthesized in four steps from (s)-(-)-1, 2, 4-butantriol and 3,4-Di-O-benzyl-glyceraldehyde(9) was prepared in five steps from commercially available, inexpensive d-mannitol. By the Wittig reaction, compound(10) was synthesized with comp.(4), comp(9) and n-Buli in -78℃. Cis isomer was obtained 4:1 ratio and observed 6:1 ratio in using of HMPA.

2-치환-4H-3, 1-Benzoxazin-4-one유도체의 합성

마은숙 대구효성가톨릭대학교 1995 연구논문집 Vol.51 No.1

Dianthalexin (7-hydroxy-2-phenyl-4H-3, 1-benzoxazin-4-one) serarated from Dianthus caryophyllus, is a kind of phytolexin. Dianthalexin was prepared by reaction of anthranilamide with acetic anhydride or thionyl chloride. In our experiments, 2-substituted-4H-3, 1-benzoxazin-4-one derivatives were synthesized by reaction of N-phenoxyacetyl-, N-(2-phenoxypropionyl)-, N-(2-phenoxybutyl)-, N-(4-t-butylbenzoyl)anthranilamide with acetic anhydride or thionyl chloride. The structures of 2-substituted-4H-3, 1-benzoxazin-4-one derivatives were idenfied with IR, NMR spectra. According to MME energy calculation method by the computer energy calculation method by the computer modeling, three dimensional structure of compounds was obtained. And MME energy and van der Waals energy were calculated by MME optimizer.

Anthranilamide유도체 합성에 관한 연구

마은숙 대구효성가톨릭대학교 응용과학연구소 1991 응용과학연구논문집 Vol.1 No.-

5-Chloro-and 5-hydroxyantranilic acid were esterified with methanol and ethanol in the presence of c-H_2SO_4. 5-Hydroxyanthranilates were reacted with p-toluenesul-fonyl chloride in triethylamine to give 5-p-toluenesulfonyoxyanthrani -late derivatives. According to Schotten-Baumann method, these compounds were reacted with phenoxyacetyl chloride and dl-2-phenoxypropionyl chloride to afford correspoding amide derivatives. And then N-substituted-5-p-tosyloxyanthranilates were reacted with NaI in dry acetone. N-phenoxyacethyl-5-iodoanthranilic acid ethyl ester was synthesized but three compounds were not reacted with NaI. The struture of synthesized compounds was identified with IR and NMR spectra.

DMSO-Acid Anhydride Mixture에 依한 糖의 酸化

김상열,마은숙 대구효성가톨릭대학교 1989 연구논문집 Vol.39 No.1

In the preparation of new carbohydrate derivatives, the synthetic uitiity of oxo compounds of monosaccharide as intermediate has provided an imspetus for the investigation of new oxidizing reagents. Since DMSO was first employed as and oxidizing agent, mixtures of DMSO and DMSO activating species(Electophile) were developed in order to oxidize the secondary hydroxy group of carbohydrates to corresponding ketones, more effectively. Starting from glucose and mannose, we synthesized their oxo derivatives by DMSO-acid anhydride method, i.e. DMSO-acetic anhydrie, DMSO-P₂O??, DMSO PPA, as activationg species. And DMSO-acid anbydride methods were compared with DMSO-oxalyl chloride and PCC method. The Structure of monosaccharide oxo derivatives were investigated by means of IR, NMR spectra.