取代吡唑-5-酰基杂环衍生物的合成、结构与生物活性

为了寻求新的含吡唑双杂环先导化合物. 用4-取代-1-甲基-3-乙基-5-吡唑甲酰氯与2-噻唑烷酮、2-噻唑硫酮、2-噁唑烷酮等含氮杂环反应得到了12个含吡唑环的双杂环化合物. 化合物结构用IR, ¹H NMR, MS和元素分析进行了表征. 并用X射线单晶衍射法测定了化合物3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噁唑烷-2-酮(3k)的晶体结构. 晶体为单斜晶系, P2₁/n (#14)空间群, a＝1.52175(3) nm, b＝0.52970(1) nm, c＝1.58185(3) nm, β＝104.893(4), V＝1.2323(4) nm³, Z＝4, D_c＝1.45 g/cm³, F(000)＝560.00, R₁＝0.064, wR₂＝0.193. 初步生物活性实验结果表明, 在25 mg/L浓度下, 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-酮(3c), 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-硫酮(3g)对水稻稻瘟病菌(Pyricularia oryzae)的抑制活性达到40%. 在500 mg/L浓度下, 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噻唑烷-2-酮(3d), 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噁唑烷-2-酮(3l)对稻黑尾叶蝉(Nephotettix cinc-ticeps)的抑制活性达到53.37%.     

合欢皮中两个新八糖苷的分离鉴定和活性研究

从合欢皮95%乙醇提取物中分离得到2个新的八糖苷(1, 2), 经化学方法与光谱分析将其结构鉴定为3-O-[β-D-吡喃木糖基-(1→2)-α-L-吡喃阿拉伯糖基-(1→6)-β-D-吡喃葡萄糖基]-21-O-[(6S)-2-反式-2-羟甲基-6-甲基-6-O-β-D-吡喃鸡纳糖基-2,7-辛二烯酸基]-金合欢酸-28-O-β-D-吡喃葡萄糖基-(1→3)-[α-L-呋喃阿拉伯糖基-(1→4)]-α-L-吡喃鼠李糖基- (1→2)-β-D-吡喃葡萄糖基酯(1)和3-O-[β-D-吡喃木糖基-(1→2)-α-L-吡喃阿拉伯糖基-(1→6)-β-D-2-去氧-2-乙酰氨基吡喃葡萄糖基]-21-O-[(6S)-2-反式-2-羟甲基-6-甲基-6-O-β-D-吡喃鸡纳糖基-2,7-辛二烯酸基]-金合欢酸-28-O-β-D-吡喃葡萄糖基-(1→3)-[α-L-呋喃阿拉伯糖基-(1→4)]-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃葡萄糖基酯(2), 分别命名为合欢皂苷J₂₅ (1, Julibroside J₂₅)和合欢皂苷J₂₂ (2, Julibroside J₂₂). 1和2在体外对4种人癌细胞增殖有明显的抑制作用.     

利用薯蓣皂甙元完整骨架形式合成1α,25-二羟基维生素D3

首次利用薯蓣皂甙元的完整骨架经16步反应以7.6%的总收率合成了骨化三醇(1α,25-二羟基维生素D₃)的光化反应前体. 3-苄基保护的薯蓣皂甙元经还原开E/F环产生3,16,26-胆甾三醇-3-苄醚(5). 除去化合物5 C-16羟基后, 其C-26羟基经消除和羟基化反应转移到C-25位. 目标分子A/B环结构单元通过薯蓣皂甙元A/B环的官能团转化被构筑. 按照已知的光化反应, (1S,3R)-胆甾-5,7-二烯-1,3,25-三醇能被转化成为1α,25-二羟基维生素D₃.     

新型多氨-多酰氨配体和氨基酸的三元铜(Ⅱ)配合物(英)

合成3个多氨-多酰氨配体1，12-二((α-羟甲基)苯基)-2，5，8，11-四氮杂十二烷-1，12-二酮(L₁)，1，13-二((α-羟甲基)苯基)-2，5，9，12-四氮杂十三烷-1，13-二酮(L₂)，1，15-二((α-羟甲基)苯基)2，5，8，11，14-五氮杂十五烷-1，15-二酮（L₃）。利用pH滴定分别在5.0 ℃，15.0 ℃，25.0 ℃，35.0 ℃测定了铜(Ⅱ)与这3种配体在     

卟啉-salen化合物的合成及谱学性质研究

合成了三种含羟基的salen化合物: salen-OH, Cl-salen-OH和t-Bu-salen-OH, 并用后两种羟基salen与5,10,15-三苯基-20-对羟基苯基卟啉(HPTPP)以烷烃链[O(CH)₆O及O(CH)₁₀O]相连合成四种卟啉-salen化合物: HPSC₆ (1), HPSC₁₀ (2), HPt-BuSC₆ (3), HPt-BuSC₁₀ (4)及其金属锌(II)化合物: ZnPSC₆ (Zn-1), ZnPSC₁₀ (Zn-2), ZnPt-BuSC₆ (Zn-3), ZnPt-BuSC₁₀ (Zn-4). 用元素分析、核磁共振、红外光谱、紫外-可见光谱等手段对其组成的结构进行表征, 并对其谱学性质进行了研究.     

哒嗪酮类α1-肾上腺素受体拮抗剂的合成和生物活性研究

将苯(氧)乙胺和苯氧烷胺类α₁-肾上腺素受体拮抗剂中的苯(氧)乙胺、苯氧烷胺片段引入哒嗪酮类化合物中, 设计、合成了30个新的含哒嗪酮环的α₁-肾上腺素受体拮抗剂. 所有新化合物的结构均经¹H NMR, IR, HRMS确证. 生物活性测试表明28个目标物对α₁-肾上腺素受体有较好的拮抗作用(pA₂＞6.00), 化合物6o, 6p, 6q, 6v, 6x, 6y, 10c, 10d的pA₂值＞7.00.     

柔荑软珊瑚Nephthea sp.中两种具有细胞毒活性的甾醇化合物

采用抗肿瘤活性追踪法对采自中国南海西沙群岛永兴岛柔荑软珊瑚Nephthea sp.中抗肿瘤活性成分进行研究, 报道了两种具有细胞毒活性的甾醇化合物, 经过MS, IR, ¹H NMR, ¹³C NMR (DEPT), HSQC 和HMBC等光谱技术鉴定为: 24-甲基胆甾-5-烯-3β,8β-二醇(1)和24-亚甲基胆甾-4-烯-3β,6β-二醇(2), 化合物1为新化合物, 利用X-ray单晶衍射技术验证化合物2的立体结构. 化合物1对肝癌细胞(BEL-7402), 小鼠白血瘤细胞(P₃₈₈)和人结肠癌细胞(LOVO)作用的IC₅₀值分别为18.0, 25.5和20.6 μg/mL; 化合物2对肿瘤细胞P₃₈₈和人乳腺癌细胞(MCF)作用的IC₅₀值分别为1.0和2.5 μg/mL.     

α-亚胺酮的不对称转移氢化合成(R)-沙丁胺醇

用手性(S,S)-Ru-TsDPEN催化剂不对称转移氢化α-亚胺酮化合物5-[(1,1-二甲基乙基)亚胺基]乙酰基-2-羟基苯甲酸甲酯(2)得光学纯β-氨基芳基乙醇类化合物(R)-5-[2-[(1,1-二甲基乙基)氨基]-1-羟乙基]-2-羟基苯甲酸甲酯(3), 再经一步还原反应即得(R)-(－)-沙丁胺醇. 对反应关键一步α-亚胺酮的不对称转移氢化反应条件进行了研究.     

3-(4-取代-哌嗪-1-甲基)-1,2,3,9-四氢咔唑-4-酮衍生物的合成与止吐活性研究

以1,3-环己二酮(1)为起始原料, 一个羰基与盐酸苯肼发生缩合反应生成1,3-环己二酮单苯腙(2), 2在ZnCl₂催化下通过分子内环合、重排反应得到1,2,3,9-四氢咔唑-4-酮(3), 3的甲基化物4在冰醋酸中经Mannich反应获得其3-二甲胺甲基物5, 5与哌嗪类化合物通过亲核取代反应合成了9个未见文献报道的3-(4-取代-哌嗪-1-甲基)-1,2,3,9-四氢咔唑-4-酮衍生物6a～6i. 所有合成的新化合物均经元素分析、红外光谱、质谱和核磁共振光谱证明其结构; 初步药理试验采用顺铂诱导的大鼠干呕模型研究了新化合物的止吐活性, 结果表明部分新化合物活性与昂丹司琼相当.     

5,6-二氢-5-氧杂-1,3-二氮杂菲衍生物的合成

以2,3-二氢-3-氧代-1,3-苯并(c)-α-吡喃(1)为起始原料, 在氢化钠作用下, 通过与羰基α-氢的Claisen缩合反应, 得到3-乙酰基-2,3-二氢-3-氧代-1,3-苯并(c)-α-吡喃(2), 所得β-二酮与脲、硫脲和脒衍生物分别进行缩合关环, 生成5,6-二氢-5-氧杂-1,3-二氮杂菲衍生物3和4. 在相同的条件下, 吡喃酮1与草酸二乙酯进行缩合反应, 给出3-乙氧乙二酰 基-2,3-二氢-3-氧代-1,3-苯并(c)-α-吡喃(5), 选择3-氨基吡唑、2-氨基咪唑、3-氨基三唑、2-氨基苯并咪唑和3,5-二氨基吡唑-4-偶氮苯与5缩合, 分别环合成5,6-二氢-5-氧杂-1,3-二氮杂菲并和五元含氮杂环衍生物6～10. 所合成的新化合物均经核磁共振光谱、红外光谱及元素分析证明其结构.     

Synthesis of 3β,20S-dihydroxydammar-24-en-12-one 3,20-di-O-β-D-glucopyranoside (chikusetsusaponin-LT8), a glycoside from Panax japonicus

A method for preparative production of 3β,20S-dihydroxydammar-24-en-12-one 3,20-di-O-β-D-glucopyranoside (1), a glycoside from Panax japonicus, chikusetsusaponin-LT₈ was developed. Chemical transformation of betulafolientriol, a component of Betula leaves extract, produced the 12-keto-20S-protopanaxadiol (3β,20S-dihydroxydammar-24-en-12-one) (2), exhaustive glycosylation of which by 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide (3) under Koenigs—Knorr reaction conditions with subsequent removal of protecting groups formed 3β,20S-dihydroxydammar-24-en-12-one 3,20-di-O-β-D-glucopyranoside (1). The principal glycosylation product was 3β,20S-dihydroxydammar-24-en-12-one 3-O-β-D-glucopyranoside if equimolar amounts of (2) and (3) were used. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 44–48, January–February, 2006.     

A new antimicrobial sesquiterpene isolated from endophytic fungus Cytospora sp. from the Chinese mangrove plant Ceriops tagal

Abstract

Chemical examination of Chinese mangrove Ceriops tagal endophytic Cytospora sp., yielded a new biscyclic sesquiterpene seiricardine D (1), and eight known metabolites, xylariterpenoid A (2a), xylariterpenoid B (2b) and regiolone (3) 4-hydroxyphenethyl alcohol (4), (22E, 24R)5, 8-epidioxy-5α, 8α-ergosta-6,22E-dien-3ß-ol (5), (22E, 24R)5, 8-epidioxy-5α, 8α-ergosta-6,9(11), 22-trien-3 ß-ol (6), ß-sitosterol (7) and stigmast-4-en-3-one (8). These structures were unambiguously elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. The antimicrobial activities of compounds 1–8 and their effects on a panel of plant and human pathogens were evaluated.     

Acetylcholinesterase inhibitory active metabolites from the endophytic fungus Colletotrichum sp. YMF432

An endophytic fungus, Chaetomium sp. YMF432, was isolated from Huperzia serrata (Thunb. ex Murray) Trev. and subjected to phytochemical investigation based on its special environment. From the extracts of fermentation solid of strain YMF 432, eight compounds including 1-O-methylemodin (1), 5-methoxy-2-methyl-3-tricosyl-1,4-benzoquinone (2), 4,8-dihydroxy-1-tetralone (3), (3β,5α,6α, 22E)-3-hydroxy-5,6-epoxy-7-one-8(14),22-dien-ergosta (4), ergosta-4,6,8(14),22-tetraen-3-one (5), β-sitostenone (6), β-sitosterol (7) and (22E,24R)-ergosta-5,7,22 -trien-3β-ol (8) were obtained. Their structures were elucidated on the basis of their spectroscopic data. These compounds were evaluated for acetylcholinesterase inhibitory activities in vitro. Compounds 1, 2, and 4 showed moderate acetylcholinesterase inhibitory activities (IC₅₀ from 37.7 ± 1.5 to 370.0 ± 2.9 μM).     

Two new 5,6-epoxysterols from calcareous marine sponge Leucetta chagosensis

Chemical investigation on CH₂Cl₂ extract of the marine sponge Leucetta chagosensis, collected from the South China Sea, afforded two new 5,6-epoxysterols, 5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (1) and (24R)-24-ethyl-5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (2) along with ten known related steroid analogs (3–12). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparison with the literature. All isolates were tested for cytotoxicity against three tumor cell lines only known compounds 11 and 12 exhibited notable cytotoxic activity against A549 (IC₅₀: 3.0 and 5.6?μM), PC9 (2.0 and 15.6?μM), and MCF-7 (9.4 and 11.8?μM) cell lines, respectively.     

Cytotoxic constituents of Lasiosphaera fenzlii on different cell lines and the synergistic effects with paclitaxel

The fruit body of Lasiosphaera fenzlii was found to show cytotoxicity on cancer cells during a preliminary screening. Repeated column chromatography of the fungal methanol extract resulted in the isolation of six compounds identified as 5α,8α-epidioxy-ergosta-6,22-dien-3β-ol (1), 5α,8α-epidioxy-ergosta-6,9(11),22-trien-3β-ol (2), 5α-ergosta-7,22-dien-3β-ol (3), 5α-ergosta-7,22-dien-3-one (4), ergosta-7,22-dien-3β,5α,6β-triol (5) and 6-dihydroxy-2,3-dihydro-1H-isoindol-1-one (6). The two peroxide compounds, 1 and 2, showed cytotoxic activity and compound 1 was selectively cytotoxic to cancer cells. Furthermore, compound 1 synergised the cytotoxicity of paclitaxel on Hela cells by increasing intracellular accumulation of paclitaxel in cancer cells but not in normal cells.     

The Neutral Part of the Bark of Pinus Taiwanensis Hayata

The neutral part of the acetone extract from the bark of Pinus taiwanensis Hayata has been Investigated and found to consist of alkanes (C₁₄-C₃₃), longifolene, aliphatic esters (C₄₂, C₄₄, C₄₉), aliphatic alcohols (C₂₄, C₂₆), 3β-21α-dimethoxyserrat-14-enc, 3β-methoxyserrat-14-en-21-one, β-sitosterol, 3β-methoxyserrat-14-en-21ã-ol and 3β-hydroxyserrat-14-en-21-one.     

A new ent-kaurane diterpenoid from Ixora amplexicaulis

A new ent-kaurane diterpenoid, 6α,16α-dihyroxy-ent-kaurane (1), was isolated from the stems of Ixora amplexicaulis, together with (24R)-6β-hydroxy-24-ethyl-cholest-4-en-3-one (2), 7β-hydroxysitosterol (3), maslinic acid (4), 3,3′-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (5) and protocatechuric acid (6). Their structures were established by extensive spectroscopic analysis, including 2D NMR techniques. Compounds 2–5 were isolated from the genus Ixora for the first time and 6 obtained originally from I. amplexicaulis.     

A new 5α,8α-epidioxysterol with immunosuppressive activity from the South China Sea soft coral Sinularia sp.

Abstract

A new 5α,8α-epidioxysterol, namely yalongsterol A (1), along with two known related steroids 5α,8α-epidioxy-24-methyl-cholesta-6,24(28)-dien-3β-ol (2) and (22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,22-dien-3β-ol (3), were isolated from the South China Sea soft coral Sinularia sp. Their structures were established by extensive spectroscopic analyses and comparisons of the spectral data with those reported in the literature. In bioassay, compounds 1–3 showed moderate immunosuppressive activities against T and/or B lymphocyte cells with IC₅₀ values ranging from 19.30 to 59.49 μM, and low cytotoxicity on murine splenocytes with CC₅₀ values ranging from 40.88 to 62.29 μM.

     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Microporotriol,a new cadinane-type sesquiterpenoid from the cultures of the wood-decay fungus Microporus affinis HFG829

Abstract

A new cadinane-type sesquiterpenoid, microporotriol (1), together with four known compound, 5-methylresorcinol (2), (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (3), (22E,24R)-ergosta-5,7,22-trien-3β-ol (4), (22E,24R)-5α,8α-epidioxy-ergosta-6,22-dien-3β-ol (5), were isolated from the fermentation broth of the wood decaying fungus Microporus affinis HFG829. The structures of the compounds were established by extensive spectroscopic methods, including 1D & 2D NMR, along with HRMS spectroscopic analysis. The relative configuration of 1 was confirmed by NMR calculation. Compound 1 was evaluated for the cytotoxicity against five human cancer cell lines.