Biotage 快速纯化制备液相色谱 Flash Isolera LS

Enzymatic synthesis of tyrosol glycosides through Biotage Isolera耐士科技

For the purpose of synthesis of tyrosol -d-glucopyranoside (salidroside) and its -d- and -d-galactopyranoside analogues, transglycosylation of tyrosol with fungal glycosidases (from Aspergillusniger and Aspergillus oryzae) was executed. Cellobiose, lactose and melibiose served as glycosyl donor giv-ing 6.7% yield of salidroside, 10.9% of tyrosol -d-galactopyranoside, and 32.2% of -d galactopyranoside.The glycosylations proceeded on the primary hydroxyl of the tyrosol.

D-Proline-based peptidomimetic inhibitors of anthrax lethal factor through Biotage Isolera耐士科技

In this work we reported the generation of D-proline-derived hydroxamic acids as inhibitors of anthrax lethal factor (LF), taking advantage of a pyrrolidine ring as the central scaffold and a hydroxamate group as the Zn2t chelating agent. The introduction of two hydrophobic groups addressing the S10 subsite and a long substrate-binding groove was conceived by overlapping the bioactive conformations of two reported LF inhibitors. Micromolar affinity of compound 38 suggested cis-3-substituted-1-sulfonamido-Dproline hydroxamic acids as a promising class of peptidomimetic inhibitors for developing novel LF inhibitors.

Dispatched and Scube Mediate the Efficient Secretion of the Cholesterol-Modified Hedgehog Ligand through Biotage Isolera耐士科技

The Hedgehog (Hh) signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesteroldependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp) and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified　Hh ligand.

Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus by Biotage Isolera耐士科技

A novel series of bis-indoles derived from naturally occurring marine alkaloid 4 were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected ‘hub proteins’ in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of cis-3-4-dihydrohamacanthin B (4) bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 10b that have similar anti-MRSA activity as compound 4. Structure–activity relationship (SAR) studies were carried out on 10b and led us to discover more potent compounds such as 10c, 10d, 10k and 10m with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with minimum inhibitory concentrations (MIC) for MRSA as low as 0.5 lg/ml. Some potent PK inhibitors, such as 10b, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Dpyk::ErmR) that lacks PK activity confirmed that bactericidal activity of 10d was PK-dependant.

Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties through Biotage Isolera耐士科技

Out of the prominent global ailments, tuberculosis (TB) is still one of the leading causes of death worldwide due to infectious disease. Development of new drugs that shorten the current tuberculosis treatment time and have activity against drug resistant strains is of utmost importance. Towards these goals we have focused our efforts on developing novel anti-TB compounds with the general structure of 1-adamantyl-3-phenyl urea. This series is active against Mycobacteria and previous lead compounds were found to inhibit the membrane transporter MmpL3, the protein responsible for mycolic acid transport across the plasma membrane. However, these compounds suffered from poor in vitro pharmacokinetic (PK) profiles and they have a similar structure/SAR to inhibitors of human soluble epoxide hydrolase (sEH) enzymes. Therefore, in this study the further optimization of this compound class was driven by three factors: (1) to increase selectivity for anti-TB activity over human sEH activity, (2) to optimize PK profiles including solubility and (3) to maintain target inhibition. A new series of 1-adamantyl-3-heteroaryl ureas was designed and synthesized replacing the phenyl substituent of the original series with pyridines, pyrimidines, triazines, oxazoles, isoxazoles, oxadiazoles and pyrazoles. This study produced lead isoxazole, oxadiazole and pyrazole substituted adamantyl ureas with improved in vitro PK profiles, increased selectivity and good anti-TB potencies with sub lg/mL minimum inhibitory concentrations.

Dereplication-guided isolation of depsides thielavins S–T and lecanorins D–F from the endophytic fungus Setophoma sp. through Biotage Isolera耐士科技

Dereplication methodology using UHPLC–DAD–QTOFMS was applied during the metabolic profiling investigation of the endophyte Setophoma sp., a fungus isolated from symptomless guava fruits. The approach performed allowed a fast analysis of the microbial secondary metabolites. From this fungus, seven highly C-alkylated depsides were isolated and identified as polyketides thielavins S, T, U and V and lecanorins D, E and F. Their structures were elucidated through spectroscopic methods including NMR, HRMS and especially with assistance of HRMS/MS experiments. The compounds were tested for quorum sensing regulation activity in the virulence gene expression of Staphylococcus aureus, but no inhibitory effect was detected. Nevertheless, moderate antibacterial activity was encountered in three of tested depsides, particularly with thielavin T, whose MIC was 6.25 lg/mL against S. aureus.

Concise preparation of novel tricyclic chemotypes fused hydantoin–benzodiazepines through Biotage Isolera耐士科技

The preparation of an indole appended vinamidinium salt, an indole appended vinylogous amide and an indole appended chloroenal are described. The subsequent regiospecific conversion of these indole containing building blocks to functionalized pyrazoles and pyrroles is detailed.

Comparison of indirect and direct quantification of esters of monochloropropanediol in vegetable oil through Biotage Isolera耐士科技

The presence of fatty acid esters of monochloropropanediol (MEs) in food is a recent concern raiseddue to the carcinogenicity of their hydrolysable moieties 2- and 3-monochloropropanediol (2- and 3-MCPD). Several indirect methods for the quantification of MEs have been developed and are commonly in use until today, however significant discrepancies among analytical results obtained are challenging their reliability. The aim of the present study was therefore to test the trueness of an indirect method by comparing it to a newly developed direct method using palm oil and palm olein as examples. The indirect method was based on ester cleavage under acidic conditions, derivatization of the liberated 2- and 3- MCPD with heptafluorobutyryl imidazole and GC–MS determination. The direct method was comprised of two extraction procedures targeting 2-and 3-MCPD mono esters (co-extracting as well glycidyl esters) by the use of double solid phase extraction (SPE), and 2- and 3-MCPD di-esters by the use of silica gel column, respectively. Detection was carried out by liquid chromatography coupled to time of flight mass spectrometry (LC–ToF-MS). Accurate quantification of the intact compounds was assured by means of matrix matched standard addition on extracts. Analysis of 22 palm oil and 7 palm olein samples (2- plus 3-MCPD contamination ranged from 0.3 to 8.8 g/g) by both methods revealed no significant bias. Both methods were therefore considered as comparable in terms of results; however the indirect method was shown to require less analytical standards, being less tedious and furthermore applicable to all type of different vegetable oils and hence recommended for routine application.

Combination of click chemistry and sulfonamides to develop three-armed triazole compounds through Biotage Isolera耐士科技

Fragment-based drug discovery is a valuable tool in hit identification, as well as the combination of different small fragments showing a minimal binding activity against biological receptors or enzymes to give merged hits. A high number of fragments on the same scaffold improve the probability to find a candidate showing single- or multi-target affinities. A rapid and versatile approach for synthesizing libraries of densely fragment-functionalized scaffolds is reported. Many fragments were assembled in few steps around a triazole ring starting from amino alcohols and other readily available building blocks. A binding assay against integrin avb3 was used as a test-bed in order to demonstrate the potential of such an approach in hit discovery strategies.

Benzoylated ethyl 1-thioglycosides direct preparation from per-O-benzoylated sugars through Biotage Isolera耐士科技

D-Glucose, lactose, maltose, and melibiose were benzoylated with Bz2O–Et3N reagent to give fully benzoylated b products. Under the same conditions, D-mannose produced a mixture where the b-benzoate predominated. Treatment of the foregoing compounds with EtSH at slightly elevated temperature (50–60 C) in the presence of BF3Et2O as a promoter gave the corresponding ethyl 1-thio glycosides in high yields. The a-products predominated in all cases in the anomeric mixtures formed. Individual products of all reactions were isolated by chromatography, they were obtained in analytically pure state, and were fully characterized by 1H and 13C NMR data and physical constants.

An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants through Biotage Isolera耐士科技

The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure–activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a Ki-value of 35.7 lM at the Dengue and 44.6 lM at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively.

An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants through Biotage Isolera耐士科技

An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile ‘click’ chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure–activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy.

A simple, cheap alternative to ‘designer convertible isonitriles expedited with microwaves through Biotage Isolera耐士科技

Interest in designer convertible isonitriles has increased in recent years with the growing recognition that isonitrile-based multi-component reactions (IMCRs) are highly effective in rapidly accessing, new and pharmacologically relevant diversity space. This Letter reports on the novel use of n-butylisonitrile as a cheaper and more atom-economical alternative to currently reported ‘designer convertible isonitriles’, facilitated by the advent of microwave-assisted organic synthesis (MAOS).

A one-pot selective synthesis of N-Boc protected secondary amines tandem direct reductive aminationN-Boc protection through Biotage Isolera耐士科技

A one-pot tandem direct reductive amination of aldehydes with primary amines resulting in N-Boc secondary amines using a (Boc)2O/sodium triacetoxyborohydride (STAB) system is reported. The tandem procedure is efficient, selective, and versatile, giving excellent yields of N-Boc protected secondary amines even in those cases where the products are prone to intramolecular lactamization.

A novel one-step microbial transformation of betulin to betulinic acid catalyzed by Cunninghamella blakesleeana through Biotage Isolera耐士科技

Betulinic acid and its derivatives are potential bioactive compounds present in nature. This study investigated the biotransformation of betulin to betulinic acid by Cunninghamella blakesleeana cells. LC–MS analysis demonstrated that betulin could be transformed into at least five products from cultured C. blakesleeana cells, among which betulinic acid was the most important. The presented method provides an attractive alternative approach to chemical synthesis, because is less time-consuming and more environmentally friendly. C. blakesleeana can transform betulin into potent derivatives with high pharmacological activities.

Biotage Flash Isolera 快速制备液相色谱视频

耐士科技作为Biotage中国区总代理，以优质的服务为您提供Biotage全系产品以及相关的技术服务。瑞典Biotage公司的产品覆盖合成实验、分离提纯、浓缩干燥、生化药物检测等一系列科学研究领域，并成为相关领域的市场领导者。 Biotage是最早推出快速制备色谱仪器的厂家，在快速制备色谱方面，市场占有率最高。

使用Biotage Isolera快速纯化液相制备色谱进行川芎中洋川芎内酯A和Z藁本内酯的分离提取

应用中压柱色谱分离提取川芎中2 个主要内酯类化合物，并对其进定性检测和结构鉴定。方法: 利用中压柱色谱分离内酯类化合物，采用120g Biotage SNAP Cartridge KP － C18 － HS 色谱柱，以乙腈－ 0. 5% 醋酸作为中压柱色谱分离剂体系，流速30 mL·min － 1 ，检测波长280 nm，柱温30 ℃，样量800 mg; 利用高效液相色谱－ 电喷雾质谱联用技术进行定性检测和结构鉴定，采用SunFireTM C18( 250 mm × 4. 6 mm，5 μm) 反相色谱柱，流速0. 5 mL·min － 1 ，正离子模式电喷雾电离，扫描范围m/z 50 ～ 1000，喷雾电压4. 5 kV，金属毛细管温度250 ℃，金属毛细管电压20 V。耐士科技作为Biotage中国区总代理，以最优质的服务给客户提供Biotage全系产品以及相关技术服务。

使用Biotage Isolera One提纯构巢曲霉 Aspergillus nidulans的次级代谢产物

通过Biotage 快速纯化系统从草酸青霉菌（Penicillium oxalicum）发酵液中分离纯化得到 24 个单体化合物，其中包括 1 个苯酞类衍生物，(3R,4S)-3,4,6,8-tetrahydroxy-3,4-dihydronaphthalen-1(2H)-one（PX-1），该化合物的绝对构型通过量子化学计算振动圆二色谱（VCD）、电子圆二色谱（ECD）及旋光光谱（OR）得到确认，结合绝对构型确定该化合物为新化合物（PX-1*）。单体化合物中还包括 8 个甾体类，3 个香豆素类，4 个苯环衍生物类，2 个二酮哌嗪类，2 个核苷酸碱基及 2 个异黄酮类化合物，这些单体结构借助核磁共振(NMR)、高分辨质谱(HRMS)及相关文献比对得到确认。

使用Biotage Isolera快速纯化液相制备色谱进行川芎化学成分的分离提取

本实验采用瑞典 Biotage 公司的 IsoleraTM型快速制备色谱仪，120g BiotageSNAP Cartridge KP-C18-HS 色谱柱，DAD 二极管阵列检测器。流动相 A：乙腈，流动相 B：0.5%醋酸水溶液，二元线性梯度洗脱条件 耐士科技作为Biotage中国区总代理，以最优质的服务给客户提供Biotage全系产品以及相关技术服务。

使用Biotage 快速纯化制备液相色谱进行哈茨木霉菌发酵液中Peptaib抗菌肽的分离纯化

粗产物利用快速色谱仪进行分离、提纯。快速色谱仪是利用 Flash 40 M cartridgesSNAP（10 g、20 g、50 g 和 100 g）正相硅胶柱安装在 Biotage flash chromatography 系统（Biotage, Dyax Corp., Charlottesville, VA）。耐士科技作为Biotage中国区总代理，以最优质的服务给客户提供Biotage全系产品以及相关技术服务。

使用Biotage 中低压制备液相色谱进行抗蛋白酶降解多肽纯化

将LHRH拮抗剂的N端转变为眠基,在其5位和6位同时引入氨基!脉基或 乙酞胺基等修饰基团,考察同时引入这些修饰基团后,LHRH拮抗剂的内生物活性及体外代谢稳定性的变化,这些修饰基团的作用是否有协等"根据多肤合成的需要,本文共合成了5个含有功能基的保护非天然氨基酸,并将这些氨基酸引入到多肤序列中,共合成了10个新结构的LHRH拮抗剂类似物,所有化合物经中压色谱纯化后,纯度经HPLC分析,均满足后期实验的要求,结构经质谱鉴定正确。耐士科技作为Biotage中国区总代理，以最优质的服务给客户提供Biotage全系产品以及相关技术服务。

通过Biotage Isolera 快速纯化制备液相进行全氟聚合物电解膜单体的提纯

耐士科技作为Biotage中国区总代理，以优质的服务为您提供Biotage全系产品以及相关的技术服务。利用PERFECT 法开发出一种新的氟化聚合物防污涂层材料CF3O( CF2CF2O) xCF2 － CONHCH2CH2CH2Si( OCH3 ) 3，该法采用了直接与氟元素氟化反应，氟化反应是该方法的一个关键步骤。通过非氟化聚乙二醇( PEG) 和全氟酰氟化物反应，得到部分氟化酯，对该氟化酯进行直接氟化，然后通过甲醇解将全氟酰氟引入到相应的化合物上，最终得到用于表面处理的涂层材料和起始物全氟酰氟化物的甲基酯

瑞典Biotage公司最新推出Isolera LS中试级快速制备色谱

耐士科技作为Biotage中国区总代理，以优质的服务为您提供Biotage全系产品以及相关的技术服务。瑞典Biotage公司最新推出Isolera LS中试级快速制备色谱,专为分离纯化大量样品设计,配备750 g和1 500 g硅胶量的SNAP专用分离柱,最多一次可分离超过150 g样品;流速最高达到500 mL /min,只需30 min就可以分离多达几十克样品;秉承了Isole ra系统的所有特点,可紫外双波长自动收集样品,固体和液体上样方式,从TLC方法直接转化为色谱的梯度方法等。该仪器特别适合分离纯化中试样品、合成样品、天然产物等。