含尿嘧啶结构单元二肽衍生物的设计、合成及生物活性研究

为探索新型抗糖尿病分子,设计了含有尿嘧啶结构单元的二肽衍生物.以尿嘧啶、多聚甲醛和半胱氨酸为原料,经过两步反应获得关键中间体S-胸腺嘧啶-L-半胱氨酸(IM-2),再经氨基保护、羧基酯化和氨基酸偶联,顺利合成了16个二肽衍生物.所得目标化合物均经1HNMR、13CNMR和HRMS进行结构确认,并开展了过氧化物酶体增殖物受体反应元件(PPRE)激动活性、α-葡萄糖苷酶-rat抑制活性、二肽基肽酶-4 (DPP-4)抑制活性筛选.生物活性结果显示,这些二肽衍生物的PPRE相对激动活性、α-葡萄糖苷酶和DPP-4抑制活性都很弱;同时发现,该类分子的α-葡萄糖苷酶抑制活性变化趋势与PPRE激动活性、DPP-4抑制活性变化趋势相反,这为新型多肽多靶点药物的设计提供了新思路.     

高效液相色谱手性固定相的研究 Ⅳ.(L,L)-二肽叔丁酰胺型手性固定相拆分α-氨基烃基膦酸衍生物对映异构体

本文制备了十种新型(L,L)-二肽叔丁酰胺型键合硅胶手性固定相,并将其用于高效液相色谱拆分外消旋α-氨基烃基膦酸衍生物。实验结果表明拆分效果良好。本文就固定相及α-氨基烃基膦酸衍生物的结构对拆分效果的影响进行了讨论,并对拆分机制进行了初步探讨。     

高效液相色谱手性固定相的研究 IV. (L,L)-二肽叔丁酰胺型手性固定相拆分α-氨基烃基膦酸衍生物对映异构体

本文制备了十种新型(L,L)-二肽叔丁酰胺型键合硅胶手性固定相, 并将其用于高效液相色谱拆分外消旋α-氨基烃基膦酸衍生物。实验结果表明拆分效果良好。本文就固定相及α-氨基烃基膦酸衍生物的结构对拆分效果的影响进行了,讨论并对拆分机制进地了初步探讨。     

高效液相色谱手性固定相的研究 IV. (L,L)-二肽叔丁酰胺型手性固定相拆分α-氨基烃基膦酸衍生物对映异构体

本文制备了十种新型(L,L)-二肽叔丁酰胺型键合硅胶手性固定相, 并将其用于高效液相色谱拆分外消旋α-氨基烃基膦酸衍生物。实验结果表明拆分效果良好。本文就固定相及α-氨基烃基膦酸衍生物的结构对拆分效果的影响进行了,讨论并对拆分机制进地了初步探讨。     

具有抗糖尿病活性（拟）二肽分子的设计、合成及生物活性

采用液相缩合法,保护的苯丙氨酸衍生物和氨基葡萄糖衍生物分别与Fmoc氨基酸偶联,简便地得到9个未见报道的L-对硝基苯丙氨酸二肽衍生物4a～i和4个2-氨基-β-D-葡萄糖拟二肽衍生物8a～d,收率为52．4％～88．1％．4a～i选择性碱性水解,得到9个对应的水解产物5a～i,收率为64．4％-90．4％．产物的化学结构经1HNMR,13CNMR和HRMS表征及证实．体外抗糖尿病活性测试结果表明,某些化合物具有很强的抗糖尿病活性,其中化合物4c和8b的过氧化物酶体增殖物激活受体反应元件（PPRE）相对激动活性分别达到150．59％和185．23％,EC50分别为1．37uM和0．64uM,作为新型抗糖尿病先导分子值得进一步研究．     

L-天门冬氨酸二肽的结构与甜味的一些关系

本文报导了一系列L-天门冬氨酸二肽衍生物,NH_2CH(CH_2COOH)CONHCH(COOCH_3)-(COX)(X为烷氧基,烷氨基,邻位取代苯胺基及N-甲基苯胺基)的合成和它们的甜度。这些二肽尾部的电性能、憎水性、以及整个分子的链长(在满足一定立体要求的条件下)都影响着二肽的甜度。     

新型光敏剂——系列尾式卟啉二肽的合成与光学性质研究

以5-(4-氨基苯基)-10,15,20-三苯基卟啉、叔丁氧羰基(Boc)保护的氨基酸为原料合成了系列新型尾式氨基酸卟啉和尾式卟啉二肽, 用核磁、质谱及元素分析对产物进行了表征, 并研究了其光学性质. 结果表明: 所合成的系列尾式卟啉二肽产率高达94%以上, 在可见光的红光部分有强烈的荧光发射.     

新型含氮杂环有机磷衍生物的合成

α-氨基膦酸的衍生物可用作除草剂[1,2]、酶合成抑制剂[3]、植物生长调节剂[4]和杀菌剂[5,6]等,近20年来,有关它的合成引起了研究者的浓厚兴趣,其中类Mannich反应合成α-氨基膦酸的衍生物,由于具有条件温和、操作方便和产率高的特点,备受关注.然而,把含氮杂环作类Mannich反应的起始原料,尚不多见.为了寻找理想活性化合物,我们用亚磷酸三苯酯、芳香醛和2-氨基-5-苯基(三氯甲基)-1,3,4-噻二唑反应,合成了11个新型含1,3,4-噻二唑的α-氯基膦酸酯衍生物,其结构得到了红外光谱、核磁共振谱、质谱和元素分析的确证,生物活性测试结果表明,它们对五种病菌均具有一定的抑制作用.     

1-取代芳基-4-乙氧羰基-5-二甲氨基亚甲基氨基-1,2,3-三唑衍生物的新法合成

以1-取代芳基-4-乙氧羰基-5-氨基-1,2,3-三唑衍生物为原料,用简单有效的方法在非常温和的条件下以较好的收率合成了一系列新型的1-取代芳基-4-乙氧羰基-5-二甲氨基亚甲基氨基-1,2,3-三唑及其衍生物,所得化合物未见文献报道.新化合物的结构用红外光谱、核磁共振、质谱和元素分析确证,同时初步研究了这些化合物的抑菌性能.     

α-氨基膦酸酯衍生物的合成及其表征

合成了一系列N端含有均三唑并噻二唑的α-氨基膦酸酯衍生物, 其结构经过红外、核磁共振氢谱、磷谱、质谱和高分辨质谱等确证.     

聚酰胺类DNA识别分子质谱的碎裂机理

采用ESI-MS法研究了8个含有N-甲基吡咯(Py)和N-甲基咪唑(Im)杂环的聚酰胺质谱的特征和碎裂机理. MSⁿ数据表明, 聚酰胺化合物的主要碎裂路径是环与环间化学键的断裂, 即C—CO键、CO—NH键、HN—C键的断裂, 同时伴随着H原子的重排. 利用这些碎裂特征, 可以得到聚酰胺丰富的结构信息和区分它们的两种同分异构体.     

MassBank: a public repository for sharing mass spectral data for life sciences

MassBank is the first public repository of mass spectra of small chemical compounds for life sciences (<3000 Da). The database contains 605 electron‐ionization mass spectrometry(EI‐MS), 137 fast atom bombardment MS and 9276 electrospray ionization (ESI)‐MSⁿ data of 2337 authentic compounds of metabolites, 11 545 EI‐MS and 834 other‐MS data of 10 286 volatile natural and synthetic compounds, and 3045 ESI‐MS² data of 679 synthetic drugs contributed by 16 research groups (January 2010). ESI‐MS² data were analyzed under nonstandardized, independent experimental conditions. MassBank is a distributed database. Each research group provides data from its own MassBank data servers distributed on the Internet. MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions. In a spectral search to retrieve mass spectra similar to a query mass spectrum, the similarity score is calculated by a weighted cosine correlation in which weighting exponents on peak intensity and the mass‐to‐charge ratio are optimized to the ESI‐MS² data. MassBank also provides a merged spectrum for each compound prepared by merging the analyzed ESI‐MS² data on an identical compound under different collision‐induced dissociation conditions. Data merging has significantly improved the precision of the identification of a chemical compound by 21–23% at a similarity score of 0.6. Thus, MassBank is useful for the identification of chemical compounds and the publication of experimental data. Copyright © 2010 John Wiley & Sons, Ltd.     

Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling

Isobaric product ions cannot be differentiated by exact mass determinations, although in some cases deuterium labeling can provide useful structural information for identifying isobaric ions. Proposed fragmentation pathways of fentanyl were investigated by electrospray ionization ion trap mass spectrometry coupled with deuterium labeling experiments and spectra of regiospecific deuterium labeled analogs. The major product ion of fentanyl under tandem mass spectrometry (MS/MS) conditions (m/z 188) was accounted for by a neutral loss of N‐phenylpropanamide. 1‐(2‐Phenylethyl)‐1,2,3,6‐tetrahydropyridine (1) was proposed as the structure of the product ion. However, further fragmentation (MS³) of the fentanyl m/z 188 ion gave product ions that were different from the product ion in the MS/MS fragmentation of synthesized 1, suggesting that the m/z 188 product ion from fentanyl includes an isobaric structure different from the structure of 1. MS/MS fragmentation of fentanyl in deuterium oxide moved one of the isobars to 1 Da higher mass, and left the other isobar unchanged in mass. Multistage mass spectral data from deuterium‐labeled proposed isobaric structures provided support for two fragmentation pathways. The results illustrate the utility of multistage mass spectrometry and deuterium labeling in structural assignment of isobaric product ions. Copyright © 2010 John Wiley & Sons, Ltd.     

Fragmentation of deprotonated cyclic dipeptides by electrospray ionization mass spectrometry

The fragmentation pathways of deprotonated cyclic dipeptides have been studied by electrospray ionization multi‐stage mass spectrometry (ESI‐MSⁿ) in negative mode. The results showed that the fragmentation pathways of deprotonated cyclic dipeptides depended significantly on the different substituents, the side chains of amino acid residues at the diketopiperazine ring. In the spectra of deprotonated cyclic dipeptides, the ion [M? H? substituent radical]^? was firstly observed in the ESI mode. The characteristic fragment ions [M? H? substituent radical]^? and [M? H? (substituent? H)]^? could be used as the symbols of particular cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment, the high‐resolution mass spectrometry (Q‐TOF) and theoretical calculations were used to rationalize the proposed fragmentation pathways and to verify the differences between the fragmentation pathways. The relative Gibbs free energies (ΔG) of the product ions and possible fragmentation pathways were estimated using the B3LYP/6–31++G(d, p) model. The results have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds and will enrich the gas‐phase ESI‐MS ion chemistry of cyclic dipeptides. Copyright © 2009 John Wiley & Sons, Ltd.     

Multidimensional Mass Spectrometry of Synthetic Polymers and Advanced Materials

Multidimensional mass spectrometry interfaces a suitable ionization technique and mass analysis (MS) with fragmentation by tandem mass spectrometry (MS²) and an orthogonal online separation method. Separation choices include liquid chromatography (LC) and ion‐mobility spectrometry (IMS), in which separation takes place pre‐ionization in the solution state or post‐ionization in the gas phase, respectively. The MS step provides elemental composition information, while MS² exploits differences in the bond stabilities of a polymer, yielding connectivity and sequence information. LC conditions can be tuned to separate by polarity, end‐group functionality, or hydrodynamic volume, whereas IMS adds selectivity by macromolecular shape and architecture. This Minireview discusses how selected combinations of the MS, MS², LC, and IMS dimensions can be applied, together with the appropriate ionization method, to determine the constituents, structures, end groups, sequences, and architectures of a wide variety of homo‐ and copolymeric materials, including multicomponent blends, supramolecular assemblies, novel hybrid materials, and large cross‐linked or nonionizable polymers.     

Effect of pH on the Metabolism of Aconitine under Rat Intestinal Bacteria and Analysis of Metabolites Using HPLC/MS-MSn Technique

A semi‐quantitative method of mass spectrometry (MS) has been described for the analysis of metabolites of aconitine by rat intestinal bacteria at different pH. At pH 7.0, the rat intestinal bacteria exhibit optimal activity for the metabolism of aconitine. A high‐performance liquid chromatography‐electrospray ionization multiple‐stage mass spectrometry (HPLC/ESI‐MSⁿ) method has been applied to investigate the characteristic product ions of metabolites. Then, the logical fragmentation pathways of metabolites have been proposed. By comparing the retention time (t_R) of HPLC and the ESI‐MSⁿ data with the data of standard compounds and reports from literature, ten metabolites have been identified and a distinctive metabolite (15‐deoxyaconitine) has been deduced first time. The experimental results demonstrate that HPLC/ESI‐MSⁿ is a specific and useful method for the identification of metabolites of aconitine. Also, in the present paper, the HPLC‐MS method was introduced to determine the synthetical metabolite prior to the study of the toxicity by the method of Bliss.     

Electrospray ionization multistage tandem mass spectrometry of penta- and hexa-substituted aryloxycyclotriphosphazenes

Several penta- and hexa-substituted aryloxycyclotriphosphazenes were synthesized and investigated by electrospray ionization tandem mass spectrometry (ESI-MSⁿ). Their main fragmentation pathways are proposed based on the MSⁿ and accurate mass data. An apparent hydrolysis reaction is an important fragmentation process exhibited in the ESI-MS/MS spectra for all of them. Also interesting is the intramolecular electrocyclic ring closure observed in ESI-MS/MS spectra of them. These observations may have some potential applications in the distinction between the mass spectra of penta- and hexa-substituted hexachlorocyclotriphosphazene derivatives.     

L‐Valine assisted distinction between the stereo‐isomers of D‐hexoses by positive ion ESI tandem mass spectrometry

The binary mixtures of 7 hexoses and 20 amino acids were investigated by electrospray ionization ion trap mass spectrometry (ESI‐ITMS). The adduct ions of the amino acid and the hexose were detected for 12 amino acids but not for the other 8 amino acids which are basic acidic amino acids and amides. The ions of amino acid–hexose complexes were further investigated by tandem mass spectrometry (MS/MS), and some of them just split easily into two parts whereas the others gave rich fragmentation, such as the complex ions of isoleucine, phenylalanie, tyrosine, and valine. We found that hexoses could be complexed by two molecules of valine but only by one molecule of the other amino acids. Among seven kinds of valine–hexose complexes coordinated by potassium ion, the MS² spectra of the ion at m/z 453 yielded unambiguous differentiation. And the fragmentation ions are sensitive to the stereochemical differences at the carbon‐4 of hexoses in the complexes, as proved by the MS². Copyright © 2010 John Wiley & Sons, Ltd.     

Atmospheric pressure ionization–tandem mass spectrometry of the phenicol drug family

In this work, the mass spectrometry behaviour of the veterinary drug family of phenicols, including chloramphenicol (CAP) and its related compounds thiamphenicol (TAP), florfenicol (FF) and FF amine (FFA), was studied. Several atmospheric pressure ionization sources, electrospray (ESI), atmospheric pressure chemical ionization and atmospheric pressure photoionization were compared. In all atmospheric pressure ionization sources, CAP, TAP and FF were ionized in both positive and negative modes; while for the metabolite FFA, only positive ionization was possible. In general, in positive mode, [M + H]⁺ dominated the mass spectrum for FFA, while the other compounds, CAP, TAP and FF, with lower proton affinity showed intense adducts with species present in the mobile phase. In negative mode, ESI and atmospheric pressure photoionization showed the deprotonated molecule [M–H]^?, while atmospheric pressure chemical ionization provided the radical molecular ion by electron capture. All these ions were characterized by tandem mass spectrometry using the combined information obtained by multistage mass spectrometry and high‐resolution mass spectrometry in a quadrupole‐Orbitrap instrument. In general, the fragmentation occurred via cyclization and losses or fragmentation of the N‐(alkyl)acetamide group, and common fragmentation pathways were established for this family of compounds. A new chemical structure for the product ion at m/z 257 for CAP, on the basis of the MS³ and MS⁴ spectra is proposed. Thermally assisted ESI and selected reaction monitoring are proposed for the determination of these compounds by ultra high‐performance liquid chromatography coupled to tandem mass spectrometry, achieving instrumental detection limits down to 0.1 pg. Copyright © 2013 John Wiley & Sons, Ltd.     

Studies on Triterpenoids and Flavones in Glycyrrhiza uralensis Fisch. By HPLC-ESI-MSn and FT-ICR-MSn

应用高效液相色谱质谱联用方法(HPLC-ESI-MSn)研究了甘草提取物中的七种化合物,四种三萜类化合物和三种黄酮类化合物。通过多极串联质谱(ESI-MSn)和多极串联傅里叶变换回旋共振质谱(FT-ICR-MSn)法研究了它们的碎裂规律。通过比较保留时间和质谱数据对上述七种化合物进行了归属,并阐述了其可能的质谱裂解途径。以上结果显示ESI-MSn和FT-ICR-MSn是非常有效的分析三萜类化合物和黄酮类化合物结构的工具。