Synthesis of enantiomerically pure (-)-(S)-brevicolline

(-)-(S)-Brevicolline (1) and related beta-carbolines were synthesized using an enantiomerically pure Michael-acceptor synthon (3). Subsequent Pictet-Spengler reaction afforded the tetrahydro-beta-carboline skeleton, which, in turn, was transformed to the beta-carboline by catalytic dehydrogenation.     

Synthesis of N-[(3S)-2,6-dioxo-1-(2-phenylethyl)-3-piperidinyl]-(2S)-2-methylbutanamide ((-)-julocrotine)

The total synthesis of (-)-julocrotine (1) starting from l-glutamic acid in 41% overall yield is described. The methodology utilizes protection, deprotection, and regioselection (carbonyl differentiation via oxazolidinone) protocols, and glutarimide ring formation is the key step.     

7-(香豆素-3-甲酰胺)-3-[1-(取代）吡啶基甲基]头孢菌素的合成

 目的：探讨3'-乙酰氧基被N-7亲核试剂取代的反应条件、分离精制方法和新头孢菌素的体外抗菌活性。方 法：7-(香豆素-3-甲酰胺)头孢菌素在Nal或KSCN的存在下与吡啶和β-甲基吡啶反应，产物用大孔吸附树脂及葡 聚糖凝胶柱层析分离。结果：合成的二个新头孢菌素化合物，由红外光谱、元素分析和核磁共振谱确证其化学结构。体外抗菌试验表明，对某些革兰阴性菌有一定的抑菌作用。结论：该反应中加入大量的Nal可缩短短反应时间并减少杂质。大孔吸附树脂可有效果将头孢菌素与无机盐分离。     

7－（香豆素－3－甲酰胺）－3－［1－（取代）吡啶基甲基］头孢菌素的合成

目的：探讨３＇－乙酰氧基被Ｎ－亲核试剂取代的反应条件、分离精制方法和新头孢菌素的体外抗菌活性。方法：７－（香豆素－３－甲酰胺）头孢菌素在ＮａＩ或ＫＳＣＮ的存在下与吡啶和β－甲基吡啶反应，产物用大孔吸附树脂及葡聚糖凝胶柱层析分离。结果：合成的二个新头孢菌素化合物，由红外光谱、元素分析和核磁共振谱确证其化学结构。体外抗菌试验表明，对某些革兰阴性菌有一定的抑菌作用。结论：该反应中加入大量的ＮａＩ可缩短反应时间并减少杂质。大孔吸附树脂可有效地将头孢菌素与无机盐分离。     

罗替戈汀手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘的合成

目的 合成罗替戈汀关键手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘.方法 以5-甲氧基-2-四氢萘酮为起始物,经过正丙胺胺化、10％钯炭催化氢化还原、手性拆分3个步骤合成得到该中间体.结果手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘的总收率为21.5％.结论该路线的原料廉价易得、收率高,适合罗替戈汀的关键手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘的工业化生产.     

Efficient total synthesis of (+)-dihydropinidine, (-)-epidihydropinidine, and (-)-pinidinone

The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (1), (-)-epidihydropinidine (2) (as HCl salts), and (-)-pinidinone (3) were efficiently synthesized from (S)-epichlorohydrin (7) as common substrate using regioselective Wacker-Tsuji oxidation of alkenylazides 10 and 14 as well as a highly diastereoselective reduction of cyclic imine 11 as key steps. The protecting group free total syntheses represent the up to date shortest routes with highest overall yields for all three naturally occurring alkaloids (1-3). The first single-crystal X-ray analysis of (-)-epidihydropinidine hydrochloride (2·HCl) confirmed its proposed absolute configuration to be (2S,6S), corresponding to that of the isolated natural product.     

N-[2-(2,4-二氟苯基)-2-羟基-3-(1H-1,2,4-三唑-1-基)丙基]-N′-(4-取代苯基)-3(2H,4H)-1,2,4-三唑酮的合成和抗真菌活性

目的寻找广谱、高效、低毒的新一代三唑类抗真菌药物。方法根据靶酶活性位点的空间特征、各种力场和关键残基分布,设计并合成了N-[2-(2,4-二氟苯基)-2-羟基-3-(1H-1,2,4-三唑-1-基)丙基]-N-′(4-取代苯基)-3(2H,4H)-1,2,4-三唑酮类化合物,并测定了体外抗真菌活性。结果体外抑菌测试结果表明,目标化合物对8种致病真菌均有一定程度的抗真菌活性,对深部真菌的活性明显优于浅部真菌。结论目标化合物对白色念珠菌均显示有较强的体外抗真菌活性,化合物1具有广谱、高活性的优点,值得进一步结构优化。     

(E)-2-[2-(4-甲氧苄基)肼基]-4-苯基噻唑与人血清蛋白的相互作用

目的: 研究(E)-2-[2-(4-甲氧苄基)肼基]-4-苯基噻唑(MHP)与人血清蛋白(HSA)之间的相互作用,为揭示噻唑类衍生物与DNA作用的机制提供实验依据. 方法: 根据MHP与HSA相互作用的荧光敏化作用,利用Stern-Volmer方程,及非辐射能量转移理论处理实验数据,采用同步荧光光谱探讨了MHP对HSA构象的影响. 结果: 实验发现MHP可以使HSA的荧光增强,表明两者之间发生了能量转移,能量转移的机理是MHP与HSA结合形成了复合物.荧光增强(敏化)效应主要源于给体-受体间的偶极-偶极作用的能量转移. 结论: 能量转移的结果为内原发色基团的荧光被猝灭和外源发色基团荧光被敏化,计算得到其敏化常数为-2.620 8×10⁴.同步荧光光谱表明,相互作用引起HSA构象变化,提示结合位点更接近于色氨酸.     

(-)-delta-N-normethylskytanthine from Tecoma arequipensis

Bark of Tecoma arequipensis yielded the major alkaloidal component (-)-delta-N-normethylskytanthine whose structure was proven by X-ray diffraction analysis of the N-thiourea derivative. The stereochemistry of 1 at all four centers was enantiomeric with that of skytanthine previously reported from Tecoma stans and Skytanthus acutus. Gc-ms of the crude base fraction indicated the presence of several related alkaloids as very minor constituents.     

Effect of phytochemicals on the mutagenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium strain TA1535

Five phytochemicals with potential chemopreventive activity were tested to determine their antimutagenic effects toward the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium strain TA1535. NNK at a concentration of 80 mM was metabolically activated by hamster liver microsomes. Three phytochemicals; capsaicin, diallyl sulphide and silymarin, exhibited antimutagenic activity toward NNK in a dose-dependent manner. At the highest nontoxic concentration tested (0.5 mmole/plate), the inhibitory effect of capsaicin, diallyl sulphide and silymarin was 85%, 23% and 48%, respectively. D-limonene and tannic acid were also tested but did not show antimutagenic activity toward NNK in TA1535. These results suggest that capsaicin, diallyl sulphide and silymarin inhibited the activation of NNK and indicate that further studies of the efficacy of these phytochemicals in the chemoprevention of NNK-induced carcinogenesis are warranted.     

(2S,3R)-1-二甲氨基-3-(3-甲氧基苯基)-2-甲基戊-3-醇的合成工艺研究

目的 对(2S,3R)- 1-二甲氨基-3-(3-甲氧基苯基)-2-甲基戊-3-醇合成工艺进行研究.方法 以3-戊酮为起始原料,经Mannich反应、手性拆分、Grignard反应等步骤合成(2S,3R)-1-二甲氨基-3-(3-甲氧基苯基)-2-甲基戊-3-醇,并对化学拆分进行工艺优化.结果 合成(2S,3R)-1-二甲氨基-3-(3-甲氧基苯基)-2-甲基戊-3-醇,总收率为30.6％.结论 工艺改进后提高了目标产物的收率,同时也减少了原料的浪费.     

板蓝根中3-（2′-羧基苯基）-1（3H）-唑酮的抗内毒素作用研究

目的 研究板蓝根中3-(2'-羧基苯基)-1(3H)-喹唑酮的抗内毒素作用.方法 将3-(2'-羧基苯基)-1(3H)-喹唑酮配成0.5%水溶液,鲎试验法进行抗内毒素定量测定;内毒素致家兔发热实验检测3-(2'-羧基苯基)-1(3H)-喹唑酮体内抗内毒素作用;脂多糖致小鼠死亡实验测定3-(2'-羧基苯基)-1(3H)-喹唑酮保护作用及3-(2'-羧基苯基)-1(3H)-喹唑酮对脂多糖致小鼠过度释放肿瘤坏死因子和一氧化氮(NO)的影响实验,研究板蓝根中3-(2'-羧基苯基)-1(3H)-喹唑酮的抗内毒素作用.结果 0.832 nag-ml-13-(2'-羧基苯基)-1(3H)-喹唑酮可使4EU内毒素降解为1.22EU,破坏率为70.56%0.5%3-(2'-羧基苯基)-1(3H)-喹唑酮溶液可使内毒素引起的家兔体温升高显著降低、使同等剂量脂多糖引起的小鼠死亡率从70%降为25%;板蓝根中的3-(2'-羧基苯基)-1(3H)-喹唑酮可抑制脂多糖致小鼠血清中TNF-a和NO的过度释放,其抑制率呈剂量依赖性.结论 从板蓝根中提取分离出的3-(2'-羧基苯基)-1(3H)-喹唑酮有抗内毒素作用.     

Expedient synthesis of (S)- and (R)-norcoclaurine from (S)- and (R)-norarmepavine [corrected] prepared by the 1-phenylethylurea method

(+/-)-Norarmepavine [3] [corrected] prepared by Bischler-Napieralski synthesis afforded, on reaction with (S)-(-)-1-phenylethylisocyanate, ureas 4 and 5 which were separated and purified by crystallization from EtOH and 70% HOAc. Alcoholysis of 4 and 5 with sodium butoxide in n-BuOH afforded (S)-norarmepavine [3a] and (R)-norarmepavine [3b] [corrected], respectively. Hplc analysis of ureas prepared from 3a and 3b with (S)-(-)-1-phenylethylisocyanate showed them to be optically pure alkaloids. Refluxing 3a and 3b with 48% HBr afforded the hydrobromide salts of (S)-norcoclaurine [1a] and its (R)-isomer 1b, respectively.     

Effect of (+/-)-, (+)- and (-)-gossypol on the lactate dehydrogenase-X activity of rat testis

The effect of (+/-)-, (+)- and (-)-gossypol on testicular lactate dehydrogenase-X (LDH-X) was studied in vitro and in vivo. It was found that racemic gossypol and the two optical enantiomers had similar inhibitory effects on rat testicular LDH-X in vitro. However, neither racemic gossypol nor the enantiomers exhibited an inhibitory effect on testicular LDH-X in vivo. It is concluded that inhibition of testicular LDH-X is not likely to be the mechanism of the antifertility action of gossypol. The inhibition of testicular LDH-X in vitro by all three preparations of gossypol is probably non-specific.     

国际血瘀证诊断指南(2021-12-16)

血瘀证是中医学常见的基本证候,在心脑血管疾病、肿瘤、糖尿病、炎症性疾病、免疫功能紊乱及组织增生等疾病的发生、发展过程中具有十分重要的作用。血瘀证诊断标准自20世纪80年代开始受到海内外医学界的高度重视,几经修订更新:1982年,中国中西医结合研究会在第一次全国活血化瘀研究学术会议上制订了《血瘀证诊断试行标准》[1]。     

(-)-Grandisin form Cryptocarya crassinervia.

The known lignan (-)-grandisin [1] has been isolated from Cryptocarya crassinervia by using the brine shrimp lethality test to direct the isolation; its structure and relative stereochemistry have been determined by ir, 1H nmr, ms, and X-ray crystallography as an all-trans alpha, alpha'-diaryl-beta, beta'-dimethyltetrahydrofuran. Compound 1 is not significantly cytotoxic in our panel of human tumor cells.     

液相色谱法制备丹参素钠

目的　分离纯化丹参中的水溶性活性成分丹参素钠。方法　采用亲脂性吸附树脂与制备型反相高效液相色谱组合分离技术 ,将丹参水提粗制品经亲脂性吸附树脂柱色谱预分离后 ,再由制备型 RP- HPL C纯化精制。结果产品经熔点、MS,IR,UV和 HPL C图谱鉴定 ,并与文献、标准对照品比较 ,证明为丹参素钠 ,纯度 >98%。结论　该方法简单 ,重复性较好 ,采用的溶剂系统价廉易得、沸点低、易于回收。