(${\pm}$)-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.

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

마은숙(Eun Sook Ma) 대구가톨릭대학교 자연과학연구소 1994 응용과학연구논집 Vol.3 No.-

환상 α,β-불포화 카르보닐 화합물의 선택적 에폭시화 및 환원

마은숙(Eun Sook Ma) 대한약학회 2005 약학회지 Vol.49 No.6

Diosgenin (25(R)-spirost-5-en-3 β-ol) was oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to form 25(R)-1,4,6-spirostatrien-3-one (1) as rigid cyclic α,β-unsaturated carbonyl compound. This compound was reacted with H2O2, m-chloroperoxybenzoic acid (mCPBA), NaOCl in the presence with (R,R)- or (S,S)-Jacobsen catalyst, tert-butyl-hydroperoxide (TBHP) in Mo(CO)6, and in VO(acac)2 catalyst, respectively. 25(R)-1,4,6-spirostatrien-3-one (1) was reduced with NaBH4, L-Selectride, LiAIH4, BH3(CH3)2S, Superhydride, Red-Al, and lithium tri-tert-butoxyaluminium hydride. And 25(R)-4,6-spirostadien-3β-ol (4) was treated with H2O2, mCPBA, TBHP in D-(-)- and L-(+)-diisopropyltar-trate and Ti(O-iPr)4 condition (Sharpless asymmetric epoxidation), TBHP in Mo(CO)6 and in VO(acac)2 catalyst, respectively.

(S)-5-요오드 -2-아미노인단·염산염의 합성

마은숙(Eun Sook Ma) 대한약학회 2001 약학회지 Vol.45 No.6

(S)-5-lodo-2-aminoindan HCI (7) was synthesized for developing a serotonergic agent. (S)-Phenylalanine was protected with trifluoroacetyl group and compound 2 was prepared by direct iodination in acetic acid and in the presence of I2, KIO4, and sulfuric acid. Compound 3 was cyclized by Friedel-Crafts reaction and reduced with NaBH4 to form 5-iodo-2-(N- trifluroacetyl) aminoindan-1-ol (4) . This compound was reduced to indan derivative 5 using the triethylsilane and BF3 · Et2O. It was basified with K2CO3 solution and treated with saturated HCI in ethyl ether to isolate compound 7.

3-멀갚토-4찌롤로피리딘의 합성

마은숙(Eun Sook Ma) 대한약학회 2002 약학회지 Vol.46 No.6

Dilithiation of 4-(pivaloylamino)pyridine (5) followed by reaction with tetraisopropylthiuram disulfide(TITD) gave rise to 3-(diisopropyldithiocarbamato) 4- pivaloylamino)pyridine (6). 3-Mercapto- 4H-pyrrolopyridine(2) was synthesized from compound 6 by two methods. The first method was that compound 6 was treated with 5M-HCI to form 2-t-butykhiazolo [5,4-c]pyridine (7) and hydrolysed in refluxing 10% NaOH and solid NaOH to prepare bis(4-amino-3-pyridyl)disulfide (8). And compound 8 was reacted with 2,5-dimethoxyteytetrahydrofuran and NaBH4 to afford compound 2. The second method was that compound 6 was hydrolysed with 10% NaOH and followed to react with 2,5-dimethox-ytetrahydmfuran to form compound 11. And then compound 11 was treated with 20% ethanolic KOH solution to synthesize compound 2.

Anthraniiamide 유도체 합성에 관한 연구

마은숙(Eun Sook Ma) 대구가톨릭대학교 자연과학연구소 1991 응용과학연구논집 Vol.1 No.-

N/A N/A

Diosgenin 유도체 합성과 진통 및 항고지혈 효과

김학순,마은숙,Kim, Hak-Soon,Ma, Eun-Sook 대한약학회 2007 약학회지 Vol.51 No.1

Twelve epoxy and hydroxydiosgenin derivatives (DI-1${\sim}$DI-12) were synthesized from diosgenin (25(R)-5-spirosten-3${\beta}$-ol). Diosgenin was epoxidized with m-chloroperoxybenzoic acid (mCPBA) to oxidize 25(R)-4${\alpha}$,5${\alpha}$-epoxyspirostane (DI-1). Diosgenin was reacted with DDQ to form 25(R)-1,4,6-spirostatrien-3-one (DI-2), which was treated with 30% H$_2$O$_2$ to give 25(R)-1${\alpha}$,2${\alpha}$-epoxy-4,6-spirostadien-3-one (DI-3) and treated with mCPBA to form 25(R)-6${\alpha}$,7${\alpha}$-epoxy-1,4-spirostadien-3-one (DI-7), respectively. DI-3 was reduced with NaBH$_4$ to afford 25(R) -1${\alpha}$,2 ${\alpha}$-epoxy-4,6-spirostadien-3${\beta}$-ol(DI-4) and reacted with Li metal in absolute ethanol to form 25(R)-2-ethoxy-1,4,6-spirostatrien-3-one (DI-5). DI-7 was reduced with NaBH$_4$ to produce 25(R)-3${\beta}$,7${\alpha}$-dihydroxy-4-spirostene (DI-8) and treated with Li metal in liquid ammonia to produce 25(R)-7${\alpha}$-hydroxy-4-spirosten-3-one (DI-9). DI-2 was reduced with NaBH$_4$ to form 25(R) -4,6-spirestadien-3${\beta}$-ol(DI-10), which was stirred with 30% H$_2$O$_2$ to synthesize 25(R)-4,6-spirostadien-3-one (DI-11) and reacted with mCPBA to give 25(R)-4${\beta}$,5${\beta}$ -epoxy-6-spirosten-3${\beta}$-ol (DI-12), respectively. The antinociceptive effects of synthesiz ed compounds were measured by hot plate method and compound DI-7 signifcantly exhibited antinociceptive effect. DI-2 decreased the serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.

6-Amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan의 합성

김민겸,마은숙,Kim, Min-Kyeom,Ma, Eun-Sook 대한약학회 2008 약학회지 Vol.52 No.1

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. Selenium was reported to have an improved antioxidant ability and to reduce the loss of dopamine. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine agonist with low neurotoxocity. In order to develop a novel dopamine agonist, we tried to synthesize the selenazoloaminoindan derivative that is a hybrid structure of aminoindan and aminoselenazole instead of aminothiazole. 2-Indanone-2-oxime was reduced with $TiCl_4$ and $NaBH_4$ to form 2-aminoindan, which was reacted with propionyl chloride to give 2-N-n-propionylaminoindan (2). Compound 2 was reduced with $TiCl_4$ and $NaBH_4$ to afford 2-N-n-propylaminoindan (3) and it was nitrated and reduced to form 5-amino-2-N-n-propylaminoindan (5), which was reacted with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5- amino-2-N-n-propylaminoindan (7) instead of selenazole ring formation. Otherwise, compound 2 was nitrated and hydrogenated to form 5-amino-2-N-n-propionylaminoindan (9), which was treated with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5-amino-2-N-n-propionylaminoindan (10). Compound 9 was cyc1ized with KSeCN and glacial acetic acid in the absence of $Br_2$ to give 6-amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan (11).

Androstane과 Cholestane 유도체의 진통, 소염 및 항고지혈 효과

김학순,마은숙,Kim, Hak-Soon,Ma, Eun-Sook 대한약학회 2007 약학회지 Vol.51 No.6

Seven epoxy- and hydroxyandrostane derivatives ($DH-1{\sim}DH-7$) and nine epoxy- and hydroxycholestane derivatives ($CH-1{\sim}CH-9$) with unsaturation in ring A and ring B were synthesized from DHEA and cholesterol, respectively. The antinociceptive effects of all synthesized compounds were measured by hot plate method. Most of androstane derivatives except $1{\alpha},2{\alpha}$-epoxy-4,6-androstadiene-3,17-dione (DH-3), and CH-6, CH-7 and CH-9 exhibited antinociceptive effect. 1,4-Androstadiene-$3{\beta},17{\beta}$-diol (DH-5, 100 mg/kg, $35.8{\pm}7.39$), $6{\alpha},7{\alpha}$-epoxy-1,4-androstadiene-3,17-dione (DH-4, 100 mg/kg, $32.6{\pm}5.50$) and $5{\alpha},6{\alpha}$-epoxy-17-oxo-androstan-$3{\beta}$-ol (DH-1, 100 mg/kg, $32.5{\pm}2.98$) were more effective than morphine (10 mg/kg, $30.6{\pm}0.5$). The analgesic effects of androstane derivatives on acetic acid writhing in mice were lower than aspirin. The androstane derivatives were less effective than ibuprofen at inhibiting effects on the carrageenin induced paw oedema. 4,6-Cholestadien-$3{\beta}$-ol (CH-5), $1{\alpha},2{\alpha}$-epoxy-4,6-cholestadien-$3{\beta}$-ol (CH-7) and $7{\alpha}$-hydroxy4-cholesten-3-one (CH-9) showed the decrease of serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.