新的氨基糖苷类抗生素HBK

氨基糖苷类的新药 HBK 是日本明治制菓(株)研制的。本药系地贝卡星(Dibekacin)的衍生物。化学名为6-O-(3-氨基-3-脱氧-α-D-吡喃葡糖)-4-O-(2,6-二氨基-2,3,4,6-四脱氧-α-D-赤-己吡喃糖)-1-N-〔(s)-4-氨基2-羟丁基〕-2-脱氧-D-链霉胺硫酸盐。     

氨基糖苷类治疗与药物监测

一、氨基糖苷类抗生素的基本骨架氨基糖苷类抗生素结构的活性中心是2-脱氧链霉胺,或称为氨基环醇,是抗菌活性的中心部分。新霉胺是含有2-脱氧链霉胺的二糖类,由2-脱氧链霉胺和新霉糖胺C(2、6-二脱氧-2、6-二氨基-D-葡萄糖)构成(图1)。     

丁胺卡那霉素(阿米卡星)

本品为0-3-氨基-3-脱氧-α-D-葡吡喃糖基-(1→6)-0-[(6-氨基-6-脱氧-α-D-葡吡喃糖基-(1→4)]-N''-(4-氨基-2-羟基-1-氧丁基)-2-脱氧-D-链霉胺。按干燥品计算,每1mg的效价不得少于910丁胺卡那霉素单位。     

白首乌化学成分研究

目的研究白首乌（Cynanchum bungei）的化学成分。方法通过多种色谱手段,对白首乌的脂溶性成分进行分离。根据化合物的波谱数据和理化常数对其进行结构鉴定。结果从白首乌中分离得到9个C21甾体苷化合物,分别为告达亭（1）、开德苷元（2）、青阳参苷元（3）、告达亭3-O-β-D-吡喃夹竹桃糖基-（1→4）-β-D-吡喃磁麻糖苷（4）、告达亭3-O-α-L-吡喃磁麻糖基-（1→4）-β-D-吡喃夹竹桃糖基-（1→4）-β-D-吡喃磁麻糖苷（5）、萝摩苷元3-O-α-L-吡喃磁麻糖基-（1→4）-β-D-吡喃磁麻糖基-（1→4）-α-L-2-脱氧毛地黄糖基-（1→4）-β-D-吡喃磁麻糖苷（白首乌苷B,6）、告达亭3-O-α-L-吡喃磁麻糖基-（1→4）-β-D-吡喃磁麻糖基-（1→4）-α-L-2-脱氧毛地黄糖基-（1→4）-β-D-吡喃磁麻糖苷（隔山消苷CIN,7）、告达亭3-O-β-D-葡萄糖基→（1→4）-α-L-吡喃磁麻糖基-（1→4）-β-D-吡喃磁麻糖基-（1→4）-α-L-2-脱氧毛地黄糖基-（1→4）-β-D-吡喃磁麻糖基苷（隔山消苷C1G,8）、开德苷元3-O-β-D-葡萄糖基-（1→4）,α-L-毗喃磁麻糖基-（1→4）-β-D-毗喃磁麻糖基．（1→4）-α-L-2-脱氧毛地黄糖基．（1→4）-β-D-吡喃磁麻糖基苷（白首乌苷A,9）。结论化合物3、4、5均为首次从本植物中分离得到。     

长药隔重楼的化学成分研究

目的 研究长药隔重楼的化学成分.方法 采用柱色谱方法单分离纯化单体化合物,通过波谱学方法鉴定其结构.结果 分离并鉴定了5个化合物,分别是△5,22-豆甾醇3-O-β-D-葡萄吡喃糖苷(I),20β-羟基蜕皮激素(Ⅱ),B-L-脱氧胸腺嘧啶苷(Ⅲ),偏诺皂苷元3-O-α-L-鼠李吡喃糖基-(1→2)-p-D-葡萄吡喃糖苷(Ⅳ)和偏诺皂苷元3-O-α-L-鼠李吡喃糖基-(1→4)-α-L-鼠李吡喃糖基-(1→4)-[α-L-鼠李吡喃糖基-(1→2)-]-β-D-葡萄吡喃糖苷(Ⅴ).结论 所有化合物均为首次从该植物中得到;其中化合物Ⅲ为首次从该属植物中分离得到.     

南山藤的化学成分研究

从萝藦科南山藤属植物南山藤的干燥茎中分离鉴定了6个化合物:β-D-黄夹吡喃糖基-(1→4)-β-D-磁麻吡喃糖基-(1→4)-β-D-阿洛吡喃糖苷(1),β-D-黄夹吡喃糖基-(1→4)-β-D-磁麻吡喃糖苷(2),marsectohexol(3),drevogenin D 3-O-β-D-磁麻吡喃糖苷(4),dregeosides Da1(5),dregeosides A11(6)。其中,化合物1为新低聚糖,化合物4为首次从属内分得C21甾体苷。     

硫酸核糖霉素

【化学名】O-β-D-呋喃核糖(1→5)-O-[α-2,6-二氨基-2,6-二脱氧-D-吡喃葡萄糖→(1→4)]-2-脱氧链霉胺硫酸盐【结构式】     

长药隔重楼中甾体皂苷成分的分离与结构鉴定

目的 研究长药隔重楼Paris polyphylla Smith varh.pseudothibetica的化学成分.方法 采用硅胶柱层析、大孔吸附树脂、葡聚糖凝胶Sephadex LH-20、预装硅胶中压柱层析及半制备RP-HPLC等技术分离纯化单体化合物,根据理化性质及波谱数据鉴定其结构.结果 从长药隔重楼乙醇提取物中分离并鉴定了8个甾体皂苷类单体化合物,分别是偏诺皂苷元-3-O-β-D-葡萄吡喃糖苷(Ⅰ)、薯蓣皂苷元-3-O-а-L-阿拉伯呋喃糖基(1→4)-[а-L-鼠李吡喃糖基(1→2)]-B-D-葡萄吡喃糖苷(Ⅱ)、薯蓣皂苷元-3-O-а-D-葡萄吡喃糖基(1→)-[а-L-鼠李吡喃糖基(1→2)]-β-D-葡萄吡喃糖苷(Ⅲ)、偏诺皂苷元-3-а-L-鼠李吡喃糖基(1→2)-B-D-葡萄吡喃糖苷(Ⅳ)、偏诺皂苷元-3-O-а-L-阿拉伯呋喃糖基(1→4)-[а-L-鼠李吡喃糖基(1→2)]-β-D-葡萄吡喃糖苷(Ⅴ)、偏诺皂苷元-3-O-а-L-鼠李吡喃糖基(1→4)-a-L一鼠李吡喃糖基(1→4)-[а-L-鼠李吡喃糖基(1→2)]-β-D-葡萄吡喃糖苷(Ⅵ)、偏诺皂苷元-3-D-β-L-鼠李吡喃糖基(1→4)-[a-L-鼠李吡喃糖基(1→2)]-β-D-葡萄吡喃糖苷(Ⅶ)、偏诺皂苷元-3-O-β-D-木呋喃糖基(1→5)-а-L-阿拉伯呋喃糖基(1→4)-[а-L-鼠李吡喃糖基(1→2)]-β-D-葡萄吡喃糖苷(Ⅷ).结论 首次从长药隔重楼中分离并鉴定出化合物Ⅰ～Ⅷ.     

瘤果黑种草子的化学成分

目的研究中药瘤果黑种草子的化学成分。方法运用多种色谱方法分离化学成分;依据这些化学成分的理化性质和波谱(NMR、EI-MS)数据分析鉴定化合物的结构。结果从瘤果黑种草子中初步分离得到5个化合物,分别鉴定为胡萝卜苷(1)、常春藤皂苷元-3-O-α-L-吡喃鼠李糖基-(1→2)-α-L-吡喃阿拉伯糖苷(2)、常春藤皂苷元-3-O-β-D-吡喃木糖基-(1→3)-α-L-吡喃鼠李糖基-(1→2)-α-L-吡喃阿拉伯糖苷(3)、3-O-β-D-吡喃木糖基-(1→3)-α-L-吡喃鼠李糖基-(1→2)-α-L-吡喃阿拉伯糖常春藤皂苷元-28-O-β-D-吡喃葡萄糖酯苷(4)、山奈酚-3-O-β-D-吡喃葡萄糖基-(1→2)-β-D-吡喃半乳糖基-(1→2)-β-D-吡喃葡萄糖苷(5)。结论化合物4为首次从黑种草属植物中分离得到,化合物5为首次从该种植物中分离得到。     

怀槐树皮异黄酮苷类化学成分研究

研究怀槐 (Maackia amurensis) 树皮中的化学成分。利用大孔吸附树脂、硅胶、凝胶和ODS柱色谱等分离技术分离化合物, 根据化合物的理化性质和光谱数据鉴定其结构。从其70%乙醇提取物的正丁醇萃取部分分离得到了13个异黄酮苷类化合物, 分别为4′,6-二甲氧基-异黄酮-7-O-β-D-葡萄糖-(1→6)-β-D-吡喃葡糖苷 (1), 樱黄素- 4′-O-β-D-葡萄糖-(1→6)-β-D-吡喃葡糖苷 (2), 芒柄花苷 (3), 黄豆素苷 (4), 染料木苷 (5), saikoisoflavonoside A (6), 阿夫罗摩辛-7-O-β-D-吡喃葡糖苷 (7), 阿夫罗摩辛-7-O-β-D-木糖-(1→6)-β-D-吡喃葡糖苷 (8), 4′-甲氧基-异黄酮- 7-O-β-D-木糖-(1→6)-β-D-吡喃葡糖苷 (9), 4′,6-二甲氧基-异黄酮-7-O-β-D-芹糖-(1→6)-β-D-吡喃葡糖苷 (10), 鸢尾种苷 (11), 5-羟基-4′-甲氧基-异黄酮-7-O-β-D-葡萄糖-(1→6)-β-D-吡喃葡糖苷 (12) 和4′-甲氧基-异黄酮-7-O-β-D-芹糖-(1→6)-β-D-吡喃葡糖苷 (13)。化合物1为新化合物, 命名为怀槐异黄酮苷(maackiaisoflavonoside), 化合物2, 8, 9, 10, 12和13为该属内首次分离得到。     

Synthesis of 1-N-(D-threo- and racemic erythro-3-amino-2-hydroxybutanoyl)-2',3'-dideoxykanamycin A

1-N-(D-Threo-3-amino-2-hydroxybutanoyl)-2',3'-dideoxykanamycin+ ++ A has been prepared by coupling of 3,6'-bis(N-benzyloxycarbonyl)-2',3'-dideoxy-3"-N-(trifluoroacetyl)kanamy cin A with D-threo-3-azido-2-hydroxybutanoic acid. A diastereomeric mixture of the erythro analog has also been prepared by use of racemic erythro-3-azido-2-hydroxybutanoic acid. Synthesis of the D-threo- and racemic erythro-3-amino-2-hydroxybutanoic acids has been described.     

1H定量核磁共振波谱法测定盐酸莫西沙星及其杂质7-氨基莫西沙星喹啉羧酸的含量

目的:建立采用1 H定量核磁共振波谱(1H quantitative nuclear magnetic resonance,1H qNMR)法测定盐酸莫西沙星及其杂质7-氨基莫西沙星喹啉羧酸对照品含量的方法.方法:采用核磁共振波谱法,使用Bruker Ascend 600超导核磁共振谱仪,以氘代二甲基亚砜(DMSO-d...     

Amikacin analogs with a fluorinated amino acid side chain

The synthesis and biological activity of kanamycin A derivatives with an omega-amino-alpha-fluoroalkanoyl side chain on the 1-amino group are described. The fluorinated amino acids (4) for the side chain were prepared by fluorination of the alpha-hydroxy esters (2) with diethylaminosulfur trifluoride (DAST) with accompanying the Walden inversion. The reaction products varied with the amino protective groups employed, chain length of the alkanoic acids and the presence or absence of base. The fluorinated side chain was introduced to 1-free-NH2 kanamycin A (12) by the conventional active ester method and subsequent deblocking reactions afforded the desired final products (13-17). Of the derivatives prepared, 1-N-[(S)-4-amino-2-fluorobutyryl]kanamycin A (2'-deoxy-2'-fluoroamikacin, 14) showed the best overall activity profile, nearly the same as that of amikacin. Preparation and antibacterial activity of several aminoglycoside antibiotics with the 1-N-(S)-4-amino-2-fluorobutyryl side chain are also discussed.     

Chemical modification of fortimicins: preparation of 4-N-substituted fortimicin B.

Among the new aminoglycoside antibiotic family for fortimicins, components A, C and D have higher activity compared to their 4-N-deacylated components B and KE. Synthesis and antibacterial activities of 4-N-acyl- and 4-N-alkyl-fortimicin B derivatives are described. 4-N-Acylfortimicin B's, which are relatively unstable in alkaline conditions, were converted to stable 4-N-alkyl derivatives with diborane. The activity is greatly affected by the 4-N-substituents, and the presence of hydrophilic group(s) is necessary to confer activity on the derivatives. 4-N-(2-Aminoethyl)-, 4-N-(4-amino-2-hydroxybutyl)- and 4-N-(2-hydroxy-4-methylaminobutyl)-fortimicin B are the most potent compounds among them.     

Synthesis and biological evaluation of carbocyclic analogues of lyxofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines

Carbocyclic analogues of lyxofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines were synthesized from (+/-)-(1 alpha, 2 alpha, 3 alpha, 5 alpha)-3-amino-5- (hydroxymethyl)-1,2-cyclopentanediol (2) and 2-amino-4,6-dichloropyrimidine (3). The 2-amino-6-chloropurine (8 and 11), the 2,6-diaminopurine (10 and 13), as well as the guanine (9) and 8-azaguanine (12) derivatives were all constructed from the key intermediate (+/-)-(1 alpha, 2 alpha, 3 alpha, 5 alpha)- 3-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-5-(hydroxymethyl)-1,2- cyclopentanediol (7) by using established methodology. Compounds 8-13 were evaluated for both antitumor and antiviral activity. None of these materials exhibited appreciable activity against P-388 mouse leukemia cells in vitro. All of these analogues were investigated for activity versus herpes simplex virus type 1 (HSV-1) and influenza virus (IV-A), as well as the human immunodeficiency virus (HIV). Against HSV-1, only compound 9, the carbocyclic analogue of the lyxofuranoside of guanine, exhibited significant activity, yielding a virus rating (VR) of 2.1. The corresponding 2,6-diamino compound (10) demonstrated marginal activity, VR = 0.6, against that virus. The test compounds failed to exhibit inhibition of either IV-A or HIV. Additionally, 9 was tested against human cytomegalovirus (HCMV) and was found to display definite activity at concentrations as low as 32 microM.     

Chinon-Amin-Reaktionen, 7. Mitt. 5-Amino-2.3.4.6-tetrahydro-benzo[f]chinoxalin-6-on

Quinone-Amine Reactions, VII: 5-Amino-2,3,4,6-tetrahydrobenzo[f]quinoxalin-6-one Aminolysis of 2,3-diphthalimido-1,4-naphthoquinone ( 15 ) by ethylenediamine ( 2 ) yields the title compound 7 as main product, which is also obtained from 18 and 2 . In addition 2,3-diamino-1,4-naphthoquinone ( 17 ) and 2-amino-3-phthalimidoethylamino-1,4-naphthoquinone ( 18 ) are formed. Attempts to produce 7 from 5-acetylamino-2,3,4,6-tetrahydrobenzo[f]quinoxalin-6-one ( 10 ) did not succeed because in acidic solution 10 is preferentially hydrolyzed to 13 whereas in alkaline solution it is dehydrogenated to 12 .     

氢核磁共振波谱法测定复方对乙酰氨基酚片中阿司匹林、咖啡因和对乙酰氨基酚

目的建立复方对乙酰氨基酚片中阿司匹林、咖啡因和对乙酰氨基酚测定的氢核磁共振波谱方法。方法采用氘代甲醇为溶剂,马来酸为内标。采用zg30脉冲序列获取~1H-NMR谱图。测试温度:300 K;谱宽:8 012 Hz;采集时间:4.01 s:弛豫时间:20 s,样品扫描次数:64次;空扫次数:2次。并采用HPLC法测定进行比较。结果阿司匹林、对乙酰氨基酚和咖啡因平均回收率分别为101.29%、101.68%、99.13%,RSD值分别为1.15%、1.73%、1.92%。qNMR法测定结果与HPLC法测定结果基本一致。结论氢核磁共振波谱法操作简便、快速,能准确测定复方对乙酰氨基酚片中阿司匹林、咖啡因和对乙酰氨基酚。     

The acetylation of 6'-amino group of amikacin by a new enzyme prepared from serratia sp

It was found that Serratia marcescens 43, Serratia proteamaculans 48 and Serratia sp. 45, all of which were clinically isolated, produced a new type of aminoglycoside acetyltransferase which acetylated amikacin at the 6'-amino group. 1-N-[(S)-3-Amino-2-hydroxypropionyl]-gentamicin B (HAPA-B, SCH 21420) and gentamicin C2 were hardly inactivated by the enzymes and had effective antimicrobial activities against these strains both in vitro and in vivo. This kind of aminoglycoside acetyltransferase should be classified into a new group other than previously reported AAC(6') enzymes.     

Total synthesis of novel antibiotics pyloricidin A,B and C and their application in the study of pyloricidin derivatives

The novel natural antibiotics pyloricidin A, B and C, which possess potent and highly selective anti-Helicobacter pylori activity, were synthesized from D-galactosamine as a chiral template for the common (2S,3R,4R,5S)-5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. The synthetic strategy, using 2-amino-2-deoxyuronic acid derivatives as key intermediates, was also useful to prepare a series of derivatives modified at the beta-D-phenylalanine and with altered stereochemistry on the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. From the drastic decrease of their anti-H. pylori activity, it was clear that the beta-D-phenylalanine part and the stereochemistry of the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety were significant for the activity.     

Central activity of new xanthone derivatives with chiral center in some pharmacological tests in mice

The study was designed to investigate some central effects of chiral xanthone derivatives [(R,S)-2-N-(6-chloro-2-xanthonemethyl)-amino-1-propanol - MH-31, R enantiomer - MH-32 and S enantiomer - MH-33] in mice. The effects of these chiral compounds were examined in picrotoxin-induced seizures, spontaneous locomotor activity and chimney tests. The tested compounds demonstrated variable influence on the central nervous system in mice. The compound MH-32 exhibits anticonvulsant activity in picrotoxin-induced seizures, whereas MH-31 and its R enantiomer--compound MH-32 demonstrated antidepressant-like activity in the forced swimming test. Moreover, all tested xanthones reduced the locomotor activity in mice. The obtained results indicate the importance to examine pharmacologically enantiomers rather than only racemic mixtures of newly synthesized compounds.