트리아졸로피리미딘계 유도체에 의한 보리 Acetolactate Synthase의 저해

김성호,남궁성건,신정휴,장수익,최정도,Kim, Sung Ho,NamGoong, Sung Keon,Shin, Jung Hyu,Chang, Soo Ik,Choi, Jung Do 대한화학회 1999 대한화학회지 Vol.43 No.4

Acetolactate synthase (ALS)는 가지를 가진 필수아미노산 Val, Leu, Ile의 생합성 과정에서 공통적으로 작용하는 효소이다. ALS는 서로 구조적 유사성이 없는triazolopyrimidine, imidazolinone,sulfonylurea, 그리고 pyrimidyl-oxy-benzoate 제초제들의 공통적인 작용 표적이다. 보리로부터 부분 정제한 ALS를 이용하여 새로이 합성한 triazolopyrimidine sulfonamide 유도체들의 저해 활성을 측정하였다. 활성을 가진 유도체들의 $IC_{50}$ 값은 0.5nM∼8${\mu}M$ 범위였으며, 그 중에서 탁월한 저해 활성을 갖는 것은 TP1과TP2 유도체로 $IC_{50}$ 값은 각각 0.5 nM과 1.6 nM이였다. 이 저해제들은 기존의 상품화된 제초제인 Metosulam ($IC_{50}$;3.6 nM), Flumetsulam ($IC_{50}$;126 nM), 그리고 Cadre ($IC_{50};4 {\mu}M$)에 비해 보리 ALS에 대한 저해 활성이 보다 우수하였다. 보리 ALS에 대한 TP2의 저해 활성은 반응시간이 증가함에 따라 증가하였고, 혼합형 저해 유형을 보였다. TP2와 imidazolinone 계열의 제초제인 Cadre, 그리고 되먹임(feedback) 저해제인 Leu에 대한 이중저해 (dual inhibition) 실험 결과 TP2와 Cadre의 경우는 평행한 반응속도론적 형태가 그러나 TP2와 Leu의 경우는 한 점에서 만나는 반응속도론적 헝태가 얻어졌다. 이는 TP2와 Cadre의 결합 부위가 최소한 부분적으로 중복되고 있음을 시사한다. Cys 잔기에 대한 화학적 변형은 TP2와 Cadre의 결합에는 영향을 미치지 않으나, Leu의 결합에는 영향을 미쳤다. Acetolactate synthase (ALS) catalyzes the first common reaction in the biosynthesis of branched-chain amino acids, valine, leucine, and isoleucine. ALS is the common target of several classes of structurally diverse herbicides, the triazolopyrimidines, the imidazolinones, the sulfonylureas, and pyrimidyl-oxy-benzoates. We examined ihibitory activities of newly synthesized triazolopyrimidine sulfonamide derivatives using partially purified ALS from barley. $IC_{50}$ values for the active derivatives are 0.5nM∼8$\mu$M. Among them TP1 and TP2 are the most potent ALS inhibitors with $IC_{50}$ values of 0.5nM and 1.6nM, respectively. These inhibitors are more potent in the inhibition of barley ALS than commercial herbicides, Metosulam ($IC_{50}$;3.6 nM), Flumetsulam ($IC_{50}$;126 nM), and Cadre ($IC_{50};4 {\mu}M$). The progress curves for inhibition of ALS by TP2 showed that the amount of inhibition increases with time. The inhibition of ALS by TP2 was mixed-type inhibition with respect to pyruvate. Dual inhibition analyses of TP2 versus an imidazolinone, Cadre, and Leu showed parallel and intercepting kinetic pattern, respectively. The results suggest that TP2 binds to ALS competively with Cadre but not with Leu. Chemical modification of cysteinly residues in ALS decreased the sensitivity of ALS to Leu, while the modification did not affect the sensitivity of ALS to TP2 and Cadre.

5, 10, 15, 20-철(Ⅱ)사페닐포르피린의 결정구조

송병호,남궁성건,유병수,Song, Byung Ho,NamGoong, Sung Keon,Yu, Byung Soo Korean Chemical Society 1997 대한화학회지 Vol.41 No.8

TTF 주게분자의 전구체로서 두 가지 다른 1,3-Dithiole-2-thione 화합물의 합성 및 특성화

김영윤,이하진,남궁성건,홍종기,노동윤,Kim, Young-Youn,Lee, Ha-Jin,Namgoong, Sung Keon,Hong, Jong-Ki,Noh, Dong-Youn 대한화학회 2000 대한화학회지 Vol.44 No.6

TTF (tetrathiafulvalene) 유도체의 전구체로서 5,6-dimethyl-1,3-dithiolo[4,5-b][1,4]dithiin-2-thione (화합물 3)을 로손반응에 의하여 합성하였다. 치환기의 종류에 따라 1,4-dithiin이나 티오펜이 포함된 두 가지의 서로 다른 생성물이 얻어졌고, 이들은 $^{13}C$ NMR과 고 분해능 전자충돌(HREI) 질량분석 분광학으로 특성화하였다. 화합물 3의 합성은 X-선 구조분석으로도 확인되었다. 결정학적 자료: 삼사정계, 공간군 P1, a=4.145(2)${\AA}$, b=10.600(2)${\AA}$, c=12.279(2)${\AA}$, ${\alpha}=71.440(10)^{\circ},\;{\beta}=84.30(2)^{\circ},\;{\gamma}=87.31(2)^{\circ}$, Z=2, $R(wR_2$)=0.0559(0.1416). 두 가지 생성물의 생성 기구를 비교하여 설명하였다. As a precursor of tetrathiafulvalene (TTF) derivative, 5,6-dimethyl-1,3-dithiolo[4,5-b][1,4]dithiin-2-thione (compound 3) was synthesized by the unusual Lawesson's reaction. Depending upon the substituents such as dimethyl and diphenyl groups, two different products containing 1,4-dithiin and thiophene moieties, respectively, were obtained and characterized by $^{13}C$ NMR and high-resolution electron impact (HREI) mass spectroscopy. The formation of 3 was further characterized by X-ray structure analysis. Crystallographic data for 3: triclinic, space group P1, a=4.145(2)$\AA$, b=10.600(2)$\AA$, c=12.279(2)$\AA$, $\alpha$=71.440(10)$^{\circ}$, $\beta$=84.30(2)$^{\circ}$, $\gamma$=87.31(2)$^{\circ}$, Z=2 and R(wR$_2$)=0.0559(0.1416). The formation mechanism of two products was suggested and compared each other.

발효 , 세포배양 , 생물공정 Phytopathogenic fungus Alternaria brassicicola SW-3 가 생산하는 항암활성 물질의 분리 정제

나여정(Yeo Jung Na),이방숙(Bang Sook Lee),남궁성건(Sung Keon Namgoong),정동선(Dong Sun Jung) 한국미생물생명공학회 2002 한국미생물·생명공학회지 Vol.30 No.1

N/A

적색 발광 물질로서 CIME 유사체들에 관한 연구

남궁성건,이경하 서울여자대학교 자연과학연구소 2005 자연과학연구논문집 Vol.17 No.-

To develope new types of red emitters, the target molecules (1-3) were designed through structural modification from DCM (A). The syntheses of the target molecules were attempted from 4-hydroxy-6-methyl-2-pyrone, as starting material through either four or six step reactions. As a result, three kinds of compounds (1-3) were prepared. The optical properties of all the synthetic compounds were examined by UV and fluorescence spectrophotometry. Photoluminescent data of each red emitters showed emission λmax values of 637 nm (DCJTB), 607 nm (1), 508 nm (2) and 598 nm (3), respectively at very dilute concentration. The band gap energies of (DCJTB and 1-3) calculated from photoluminescent spectra were 2.12, 2.27, 2.35 and 2.46 eV, respectively. The relative quantum yields of the red emitters (DCJTB and 1-3) determined by fluorescence spectroscopic analysis were 11, 24, 0.3 and 10%, respectively. Throughout observation of all the optical data, DCJTB is the most efficient red emitter to display emission λmax value around 650 nm. The compound (1) has the highest relative quantum yield among the materials described in this research.

DNA-Transfection을 위한 양이온성 리포좀에 포함되는 Phytosphingosine 유도체의 개발

남궁성건,박선이 서울여자대학교 자연과학연구소 2001 자연과학연구논문집 Vol.13 No.-

본 연구에서 합성한 TMPㆍI를 함유하는 양이온성 리포좀(TMPㆍI : DOPE = 1 : 1(무게비))으로 in vitro 계에서 유전자 전달 실험을 수행한 결과, L/D 비가 증가할수록 유전자 전달 정도가향상되었고 TMPㆍI는 리포좀 종류에 따라 유전자 전달 정도의 차이를 나타냈는데 SUV 보다 MLV일 때 그 효율이 1 5배 더 증가하였다. DOPE/phytoS(1 : 1 무게비)로 구성된 대조 리포좀의 유전자 전달 효율은 L/D 비가 20에서도3% 정도에 불과한데 비하여 phytos의 아민기에트리메틸레이션한 TMPㆍI를 함유하는 양이온성 리포좀은 11%로 유전자 전달 효율을 3 ~4배 정도 증가시킴을 확인할 수 있었다. 또한 기초적인 생물학적 테스트를 통하여 TMPㆍI를 포함하는 양이온성 리포좀은 TMS를 포함하는 리포좀보다 훨씬 뛰어난 암 전이 억제 효파 및 성장 억제 기능도 나타냄을 알 수 있었다. N,N,N-Trimethylphytosphingosinium iodide (TMPㆍI), a derivative of phytosphingosine(PhytoS), contained in cationic liposome was used to examine its DNA transfection efficiency in BHK cell line in vitro. The result in DNA transfection assay showed that DOPE/TMP liposome was more effective than the control group, DOPE/PhytoS. Unlike conventional liposomes, the liposome comprising TMPㆍI exhibited a high DNA transfection efficiency and it will be very useful tool in developing the delivery system of gene with antitumor activity.

D-Phytosphingosine으로부터 safingol의 합성에 관한 연구

남궁성건,박선경 서울여자대학교 자연과학연구소 2005 자연과학연구논문집 Vol.17 No.-

A novel synthesis of safingol (L-threo-dihydrosphingosine) was attempted from D-phytosphingosine. As a result, the precursor (6) of safingol was prepared in a form of mixture with minor precursor (7) of sphinganine from starting material through four step reactions in 45% overall yield. The diol (2) was produced by BOC and TBDPS group protection reactions on C-1 and 2 amino alcohol functionalities of D-phytosphingosine in 81% overall yield. An inseparable mixture of the desired epoxide (5) and the other diastereomer (4) was obtained from the diol (2) in single step epoxidation reaction. Their ratio was 5:1, generating the compound (5) as a major product in 70% yield. Regioselective C-4 ring-opening reaction for the diastereomeric mixture of the epoxides (4) and (5) at C-4 position with DIBAH also gave the inseparable mixture of precursors (6) and (7) with a ratio of 4:1 in 70% yield.

(-)-Ovalicin 유도체의 핵심 중간체에 대한 합성

남궁성건,이방숙,김은옥 서울여자대학교 자연과학연구소 2002 자연과학연구논문집 Vol.14 No.-

본 연구에서는 새로운 형태의 antl-angiogenic agent를 개발하기 위하여 anti-angiogenic activity를 나타내는 (-)-Ovalicin 의 구조를 변형한 target molecule (3)을 설계하고 이 화합물의 합성을 위한 핵심 중간체인 화합물 (5)를 합성하였다. 핵심 중간체 (5)는 출발 물질인 (-)-quinic acid로부터 합성하였는데 먼저 산 촉매 존재 하에 (-)-quinic acid 의 C-4, 5 위치에 acetal protection과 동시에 C-1, 3 위치에 lactone formation 및 lactone (6) 의 methanolysis를 통하여 화합물 (7)을 합성 한 다음 sec-alcohol group의 oxidation과 tert-alcohol group의 chlorination 및 C-1, 2 위치에 연속적인 elimination으로 conjugation된 ester (8)을 얻었다. 화합물 (8)의 bezylidene acetal deprotection 과 diol (9)에 silyl group protection 및 화합물 (10)에 NaBH₄를 사용한 선택적인 carbonyl group reduction을 통하여 화합물 (11)을 합성하였다. Alcohol (11)의 methylation과 ester (12) 의 DIBAH reductioin 및 화합물 (13) 의 al1ylic double bond 에 stereoselective epoxidation으로 핵심 중간체 (5)를 얻었으며 전체적으로는(-)-quinic acid로 부터 10단계의 합성 과정을 거쳐 6%의 총 수율로 핵심 중간체 (5)를 합성하였다. 핵심 중간체 (5) 로부터 화합물 (4)를 포함한 4-6 단계의 합성 과정을 통하여 target molecule (3) 을 얻을 수 있을 것으로 기대된다. To develope new type of anti-angiogenic agent, the target molecule (3) was designed through structural modification from (-)-Ovalicin. Its key intermediate (5) for the synthesis of the target molecule (3) was synthesized from (-)-quinic acid, as a starting material. Acetal protection at C-4, 5 position, followed by simultaneous lactone formation at C-1, 3 position of (-)-quinic acid in the presence of acid catalyst and methanolysis of the lactone (6) gave the compound (7). Oxidation of the sec- alcohol group, chlorination of the tert-alcohol group, sequential elimination at C-1, 2 position of the compound (7) produced the conjugated ester (8). Benzylidene acetal deprotection on the compound (8), introductioin of silyl protecting groups to the diol (9) and selective carbonyl group reduction of compound (10) with NaBH₄ gave the alcohol (11). Methylation of the alcohol (11), reduction of the ester (12) with DIBAH and stereoselective epoxidation at the allylic double bond of the compound (13) produced the key intermediate (5). In summary, the key intermediate (5) was synthesized from (-)-quinic acid through 10 reaction steps in 6% overall yield. The target molecule (3) is expected to be obtained from the key intermediate (5) via the compound (4) through 4-6 reaction steps.

적색 발광 물질로서의 Pyran 유도체들에 관한 연구

남궁성건,이경하,안현진 서울여자대학교 자연과학연구소 2003 자연과학연구논문집 Vol.15 No.-

모든 실험 결과를 종합해보면 합성한 물질들 중 650 nm 근처의 λ_(max)(emission spectrum) 값을 보이면서 비교적 나은 양자효율을 갖는 red dopant 는 새로운 화합물 (5) (λ_(max): 644 nm)로 판단된다. 또한 개발된 물질을 소자의 제조에 적용할때 물질은 진공 증착과정을 거쳐 소자에 박막으로 도입되는데 이때 물질 자체의 녹는점이 200℃ 이상 되는 것이 바람직하다. 이상적인 red dopant 의 개발을 위하여 화합물 (5)의 물리화학적 및 광학적 성질들 가운데 개선되어야 할 부분은 녹는점 (177-178℃) 과 양자효율 (37%)이 해당된다. 최소 200℃ 이상의 녹는점과 더 높은 양자효율을 나타내야 이상적인 red dopant의 역할을 할 것으로 기대되며 이를 위하여서는 화합물 (5)의 thiobarbituric acid와 pyran ring이 연결된 기본골격은 그대로 유지하면서 pyran ring의 2- 또는 6-위치에 전자를 좀더 강력하게 줄 수 있되, rigid conformation을 갖는 새로운 group을 도입하는 것이 바람직하며 이들의 합성은 본 연구의 합성결과와 같이 짧은 합성과정을 통하여 이루어지는 것이 효과적일 것이다. To develope new types of red emitters, the target molecules (3a-5a) and (3-5) were designed through structural modification from DCM (1). The syntheses of the target molecules were attempted from both 2,6-dimethyl-4H-pyran-4-one and 4-hydroxy6- methyl-2-pyrone, as starting materials through either two or four step reactions. As a result, four kinds of compounds (3a) and (3-5) were prepared. On the other hand, the other compounds (4a) and (5a) were not able to be obtained due to serious purification problem of byproducts. The optical and electrical properties of all the synthetic compounds shown in Table 1 were examined by UV and fluorescence spectrophotometry and cyclic voltammetry, Photoluminescent data of each red emitters showed absorption λ_(max) values of 480 nm (3a, 3), 511 nm (4) and 539 nm (5) and emission Amax values of 588 nm (3a), 585 nm (3), 623 nm (4) and 644 nm (5), respectively at very dilute concentration. The relative quantum yields of the red emitters (3a, 3-5) determined by fluorescence spectroscopic analysis were 37, 39, 13, 37%, respectively. The band gap energies (E_(g)) of (3a, 3-5) calculated from cyclic voltammogram were 2.21, 2.28, 2.13 and 2.01 eV, respectively. This electrochemical experiment indicated that there is almost no difference between band gap energies determined by both fluorescence spectroscopic method and cyclic voltammetry. Throughout observation of all the optical and electrical data, the compound (5) has the most electron-accepting ability and is the most efficient red emitter among the materials synthesized in this research.

폴리펩타이드로 구성된 새로운 키랄,거대고리 상 이동 촉매의 합성에 관한 연구

남궁성건,고윤주 서울여자대학교 자연과학연구소 2000 자연과학연구논문집 Vol.12 No.-

We designed the chiral, macrocyclic phase transfer catalyst (3) mixed with both chemical characters of catalyst (1) and preorganized conformation of receptor (2a-b). It may be the more efficient catalyst in the sense of structural features relative to compound (1) and (2a-b). It was necessary that the standard compound (4) similar to the structure of compound (3) was synthesized to confirm the stability and solubility of quaternary ammonium salt (3). The compound (4) was obtained from 3,5-pyridinedicarboxylic acid through 6 steps in overall 35% yields according to scheme 1. The chemical properties of compound (4) were satisfied in various phase transfer reactions. The synthesis of compound (3) has been attempted according to scheme 2. At present, precursor (3a) was produced from 3,5-pyridinedicarboxylic acid through 21 steps in overall 1.9% yields. The compound (3) that can be obtained by sample alkylation of the precursor (3a) will be applied to various phase transfer catalyses requiring asymmetric induction or kinetic resolution.