• 제목/요약/키워드: Ketone

검색결과 655건 처리시간 0.03초

Potential Antitumor $\alpha$-Methylene-$\gamma$-butyrolactone-Bearing Nucleic Acid Base. 3. Synthesis of $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans

  • Kim, Jack-C.;Kim, Si-Hwan;Kim, Ji-A;Choi, Soon-Kyu;Park, Won-Woo
    • Archives of Pharmacal Research
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    • 제21권4호
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    • pp.458-464
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    • 1998
  • Search for a new $\alpha$-methylene-$\gamma$-butyrolactone-bearing 6-substituted purine as a potental antitumor agent has led to synthesize seven, hitherto unreported, $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$- methylenetetrahydrofurans (H, Cl, l, $CH_3$, $NH_2$, SH, >C=O) (6a-g). These include $5^1$-Methyl-$5^1$-[(9H-purin-9-yl)methyll-$2^1$-oxo-$3^1$ -methylenetetrahydrofurans (6a), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydr ofurans (6b), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6c), $5^1$-Methyl-$5^1$-[(6-methyl-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6d), $5^1$-Methyl-$5^1$-[(9H-adenin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6e), $5^1$-Methyl-$5^1$-[(6-mercapto-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6f) and $5^1$-Methyl-$5^1$-[(9H-hypoxanthin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrof urans (6g) which were made by the Reformatsky-type reaction of ethyl $\alpha$-(bromomethyl) acrylate with the corresponding (6-substituted-9H-purin-9-yl)-2-propanone intermediates (5a-g). These ketone intermediates 5a-g, 1-(9H-purin-9-yl)-2-propanone (5a), 1-(6-chloro-9H-purin-9-yl)-2-propanone (5b), 1-(6-iodo-9H-purin-9-yi)-2-propanone (5c), 1-(6-methyl-9H-purin-9-yl)-2-propanone (5d), 1-(9H-adenin-9-yl)-2-propanone (Se), 1-(6-mercapto-9H-purin-9-yl)-2-propanone (5f), and 1-(9H-hypoxanthin-9-yl)-2-propanone (5g) were directly obtained by the alkylation of the 6-substituted purine bases with the chloroacetone in the presence of $K_2$$CO_3$ (or NaH) under DMF (or DMSO). The preliminary in vitro cytotoxcity assay for the synthetic .alpha.-methylene-y-butyro-lactone compounds (6a-g) were determined against three cell lines (PM-3A, P-388, and K-562) and showed the moderate antitumor activity ($IC_50$ ranged from 1.4 to 4.3 $\mu\textrm{g}$/ml) with the compound $5^1$-methyl-$5^1$ -[(9H-hypoxanthin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofuran (6g) showing the least antitumor activity.

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$[^{123}I]$Idoxifene 합성과 유방암의 세포섭취에 관한 연구 (Study for the Synthesis of $[^{123}I]$Idoxifene and Its Uptake in the Breast Cancer Cell)

  • 조영섭;양승대;서용섭;전권수;안순혁;임수정;임상무;유국현
    • 대한핵의학회지
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    • 제34권5호
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    • pp.410-417
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    • 2000
  • 목적: 현재 유방암 치료제로서 임상실험 제 2단계에 들어간 idoxifene은 항에스트로겐 의약품으로서 기존의 tamoxifen보다도 많은 장점을 가지고 있는 것으로 연구결과 밝혀졌다. 또한 방사성 동위원소 $[^{123}I]$를 표지한 $[^{123}I]$idoxifene은 SPECT을 이용한 유방암세포를 영상화하여 조기에 진단할 수 있는 진단시약으로서 널리 각광 받고 있다. 따라서 본 연구에서는 idoxifene의 전구체를 합성하고 $[^{123}I]$를 표지하여 세포 내 섭취론 관찰하였다. 대상 및 방법: $[^{123}I]$idoxifene을 위한 전구체는 McCague가 연구 발표한 자료를 바탕으로 (2-chloroethoxy)benzene과 2-phenylbutanoic acid를 출발물질로 하여 합성하였다. 표지는 $[^{123}I]$를 사용하였으며 분리는 Silica Sep-Pak을 사용하였으며 세포 내 섭취실험은 에스트로겐 리셉터를 가진 MCF-7과 대조군으로서 에스트로겐 리셉터가 없는 MDA-MB-468을 이용하였다. 결과 및 결론: Idoxifene의 전구체인 4-stannylated 화합물의 합성수율은 약 30%이었으며, $[^{123}I]$ 표지는 60분 경과에서 $90{\sim}92%$로 최대의 표지수율을 보였으며 방사화학적 순도는 98%이상이었다. 또한 세포 내 섭취실험에서 실험군과 대조군 사이에 섭취비율은 180분에서 1.7:1로 나타나 idoxifence은 항에스트로겐 효과가 아주 높은 것으로 판명되었다. 이를 바탕으로 배양세포와 동물모델을 이용한 추가적인 실험이 필요하며, 유방암 환자에게도 임상이용이 기대된다.

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멀티 선회류식 세정장치를 이용한 고효율 하이브리드 VOCs 습식처리 SYSTEM 개발 (Development of VOCs Treatment Technology using High Efficiency Hybrid System with Multi-Scrone)

  • 임성일;김로중;김선미;이성훈;김선욱;장원석;박대원;김래현;김재형
    • 대한환경공학회지
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    • 제31권7호
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    • pp.491-498
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    • 2009
  • 본 연구에서는 환경기초시설과 정유공장, 도장시설 등에서 발생하는 악취 및 휘발성 유기화합물(VOCs:Volatile Organic Compounds)을 처리하는데 주로 사용되는 RTO와 RTO를 대체할 수 있는 중저가의 고효율 처리기술을 개발하고자 하였다. toluene, xylene, benzene, MEK, ethanol, hydrogen sulfide, formalin 등을 처리대상 VOCs와 악취물질로 선정하고 처리방식은 1차로 선회류식 세정장치를 이용하여 친수성의 악취 및 VOCs를 제거하고 2차로 섬유상 바이오필터를 이용하여 친수성 VOCs 뿐만 아니라 소수성 VOCs를 모두 효율적으로 처리하는 하이브리드 기술을 개발하는 동시에 VOCs 처리장치의 크기를 컴팩트하게 하는데 주안점을 두었다. 선회류식 세정장치에서 첩족시간을 2~3초로하고 세정수를 비격막식 전해수로 사용하였을 때 친수성 VOCs 물질인 ethanol과 상대적으로 친수성 악취물질인 hydrogen sulfide는 각각 95~99%, 93~97%로 거의 완벽하게 제거되었다. 또한 MEK, formalin의 처리효율은 각각 78~90%, 72~85%로 높은 제거효과를 나타내었다. 반면에 소수성 물질인 toluene, xylene, benzene에 대한 선회류식 세정장치의 처리효율은 각각 16~22%, 12~18%, 8~16%으로 낮게 나타났다. 하지만 일정한 처리효율을 계속 유지함을 확인할 수 있었다. 섬유상 바이오필터는 toluene의 경우 초기에는 처리효율이 좋지 않았지만 순응기간인 7~10일정도가 지난 이후부터는 미생물 분해처리를 통해 70% 이상의 제거율을 보였으나 이후 85~95%의 처리효율을 보였다. 하지만 MEK가 혼합된 단계에서는 5~10%정도의 처리효율 감소경향을 나타내었는데 이는 미생물들이 처리하기 쉬운 MEK를 우선 처리하는 성향때문이라고 사료된다. MEK에 대한 섬유상 바이오필터의 처리효율은 80~92%로 안정적인 처리효율을 보였다. 경제성 측면에서도 소각방법인 RTO 대비 시설비 및 유지관리비를 절감할 수 있어 중, 저가 VOCs 처리기술로 각광받을 것으로 사료된다.

동충하초 균사체로 발효시킨 백련잎차의 품질특성 (Quality Properties of White Lotus Leaf Fermented by Mycelial Paecilomyces japonica)

  • 김종숙;왕수빈;강성구;조영숙;박석규
    • 한국식품영양과학회지
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    • 제38권5호
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    • pp.594-600
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    • 2009
  • 눈꽃 동충하초 균사체를 이용한 백련잎 발효차와 비발효차의 열수와 에탄올 추출물에 대한 품질특성을 평가하기 위하여, 추출수율, 갈변도, 유리당, 유기산, 유리아미노산, 무기질의 함량을 조사하였고, 또한 수증기 증류법으로 백련잎차의 휘발성 성분을 동정하였다. 추출수율은 발효 및 비발효차 모두 열수 추출물이 에탄올 추출물보다 높았으며, 백련잎 발효차의 열수 추출용매에서 유의적으로 가장 높은 26.55%를 나타내었고(p<0.05), 갈변도는 흡광도로서 열수 추출물이 에탄올 추출물에 비하여 1.6배 이상으로 높은 값을 나타내었다. 총 유리당은 백련잎 발효차의 열수 추출물에서 43.4%로 가장 높은 함량을 나타내었으며, glucose 함량은 발효차의 열수 및 에탄올 추출물에서 각각 5.6배, 3.7배 유의적으로 증가되었다(p<0.05). 총 유기산은 $861.9{\sim}4,704.8\;mg%$ 범위로서 발효 백련잎차의 에탄올 추출물이 가장 높았으며, 그 중에는 succinic acid가 에탄올 추출물에서 유의적으로 가장 높았고(p<0.05), 백련잎 발효차는 비발효차의 경우와는 달리 acetic acid, malic acid, tartaric acid가 확인되었다. 총 유리아미노산은 건물 당 $346.4{\sim}1,480.8\;mg%$ 범위 로서, 비발효 백련잎차의 열수 추출물이 가장 높은 함량을 나타내었다(p<0.05). 백련잎 발효차는 비발효차에 비하여 총 유리아미노산 함량이 감소하는 경향이었으며, 용매별로는 열수 추출물이 에탄올 추출물에 비하여 2.9배 유의적으로 높았고(p<0.05). 총 무기질은 비발효 및 발효차의 열수 추출물이 에탄올 추출물에 비하여 각각 2.1배, 1.7배 높았으며, 그 중에서는 발효차의 열수 추출물이 유의적으로 가장 높은 함량을 나타내었다(p<0.05). 휘발성 성분은 aldehyde류 11종, alcohol류 14종, ketone류 11종, hydrocarbone류 11종, acid류 12종으로 총 59개를 동정할 수가 있었으며, 특히 비발 효차는 alcohol류, 발효차는 aldehyde류와 ketone류에서 서로 다른 휘발성분들이 확인되었다.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2016년도 춘계학술대회 및 임시총회
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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