内氢键对芳环~(13)C化学位移的影响

本文讨论水杨醛、邻——基苯乙酮及2——基雌甾化合物的分子内氢键对芳环~13C化学位移的影响。采用量子化学CNDO/2方法,计算取代芳烃各原子的净电荷,从碳原子的净电荷与化学位移的对应关系进一步论证了此种影响.首次得到形成内氢键的甲甲基、乙乙基及及基对所在碳的取代基增量的校正值,经校正后化学位移的计算值与实测值很好符合。     

具有特殊甾核结构甾体化合物的合成及生理活性研究进展

改变甾体的甾核结构,在甾核或支链中引入不同的官能团,可以得到一些具有不同生理活性的化合物.按照不同类型甾核结构分类,结合本课题组在具有特殊甾核结构甾体化合物的合成和生理活性研究方面所取得的一些成果,对近年来具有A-失碳甾体化合物、B-失碳甾体化合物及C-失碳-D-增碳甾体化合物的合成及生理活性进行讨论,并展望了此类化合物的发展趋势及应用前景.     

△^9^(^1^1^)雌甾四烯类化合物的硼氢化-铬酸氧化(I)

本文简要报道了雌甾四烯类化合物的硼氢化-铬酸氧化反应。     

甾体-卟啉化学的研究

通过雌甾-卟啉的键链, 合成了四个卟啉-甾体化合物. 并用紫外、核磁、红外和元素分析鉴定了它们的结构. 并用差热分析证明它们各含一分子结晶水.     

雌甾的双羟甲基化和双咪唑甲基化反应

本文报道雌甾A环的直接双羟甲基化和双咪唑甲基化反应。将雌二醇(ia)、炔雌醇(ib)、雌酚酮(ic)及其17-正的醇缩酮(id) 分别与甲醛和粉状氢氧化纳于少量溶剂中在50~550 反应,生成对应的2,4-二(羟甲基)雌甾化合物2a~d。将(a,b,d分别与聚甲醛和咪唑在130~141 反应或将双羟甲基化反应可得的2a,b,d 与咪唑反应均生成对应的2,4-二(咪唑甲基)雌甾化合物3a,b,d。     

雌甾-卟啉及其金属配合物的合成

为了研究仿酶模型, 并探索具有催化活性甾体物质, 本文将雌甾与金属卟啉键联, 希望通过甾体的疏水模板作用, 以获得比单纯金属卟啉活性更高的仿酶模型。因此,本文合成了三个雌甾卟啉及其十二个金属配合物, 这些化合物结构经过UV-VIS、IR、^1HNMR及元素分析鉴定。     

3-羟基雌甾-1,3,5(10),15-四烯-17-酮的高效合成

以雌酚酮为原料,以取代的苯甲酰作为雌酚酮酚羟基的保护基,乙二醇为雌酚酮羰基的保护基,经过溴代、脱溴和水解等5步反应,通过优化反应路线、反应试剂及反应条件,以65%的高收率制得3-羟基雌甾-1,3,5(10),15-四烯-17-酮.中间体及目标产物的结构经过元素分析、核磁共振波谱(NMR)和电喷雾电离-质谱(ESI-MS)确证.     

△~9(11)雌甾四烯类化合物的硼氢化-铬酸氧化(Ⅰ)

雌甾-11-酮化合物是合成11-烃基取代甾体化合物的关键中间体。文献多采用硼氢化-过氧化氢氧化得11α-羟基物,再经进一步氧化得雌甾-11-酮化合物。两步反应均有副产物生成,总收率很低(31%)。Brown 等报道有机硼烷化合物用重铬酸钠的硫酸水溶液氧化可直接得到酮。我们将此     

△^9^(^1^1^)-雌甾四烯类化合物的硼氢化-铬酸氧化 II

雌甾-11-酮化合物是合成具有强效抗生育活性11-烃基取代在甾体化合物的关键中间体。本文对13β-乙基-3-甲氧基-甾-1,3,5(10), 9(11)-四烯-17β-醇的硼氢化-铬酸氧化反应进行研究, 结果发现产物比较复杂, 在温和条件下, 主要产物为13β-乙基-3-甲氧基-甾-1,3,5(10)-三烯-17-酮-112-硼酸, 增加氧化剂用量, 延长反应时间则得到11,17-二酮。     

雌甾-卟啉仿酶模型化合物的合成、构型与反应性

17β-雌二醇与氯乙酰氯反应所得产物2与卟啉1反应, 合成了雌甾-双卟啉二聚体3及雌甾单卟啉4。引入金属后得到雌甾-卟啉钴仿酶模型化合物3a及4a。它们的结构与构型经UV-Vis,IR, 1H NMR和元素分析确证, 并考查了3a对氢醌氧化反应的催化性能。     

Gas‐phase fragmentation of protonated piplartine and its fungal metabolites using tandem mass spectrometry and computational chemistry

Piplartine, an alkaloid produced by plants in the genus Piper , displays promising anticancer activity. Understanding the gas‐phase fragmentation of piplartine by electrospray ionization tandem mass spectrometry can be a useful tool to characterize biotransformed compounds produced by in vitro and in vivo metabolism studies. As part of our efforts to understand natural product fragmentation in electrospray ionization tandem mass spectrometry, the gas‐phase fragmentation of piplartine and its two metabolites 3,4‐dihydropiplartine and 8,9‐dihydropiplartine, produced by the endophytic fungus Penicillium crustosum VR4 biotransformation, were systematically investigated. Proposed fragmentation reactions were supported by ESI‐MS/MS data and computational thermochemistry. Cleavage of the C‐7 and N‐amide bond, followed by the formation of an acylium ion, were characteristic fragmentation reactions of piplartine and its analogs. The production of the acylium ion was followed by three consecutive and competitive reactions that involved methyl and methoxyl radical eliminations and neutral CO elimination, followed by the formation of a four‐member ring with a stabilized tertiary carbocation. The absence of a double bond between carbons C‐8 and C‐9 in 8,9‐dihydropiplartine destabilized the acylium ion and resulted in a fragmentation pathway not observed for piplartine and 3,4‐dihydropiplartine. These results contribute to the further understanding of alkaloid gas‐phase fragmentation and the future identification of piplartine metabolites and analogs using tandem mass spectrometry techniques. Copyright © 2017 John Wiley & Sons, Ltd.     

药物泰瑞沙的质谱分析及其未知杂质的结构解析

利用气相色谱-质谱法在电子电离源下对用于治疗肺癌的药物泰瑞沙(Tagrisso)进行分析,对主成分奥斯替尼(Osimertinib)在质谱中产生的主要的碎片离子进行归属,推测其可能的质谱裂解途径。参考主成分奥斯替尼的质谱裂解方式,由质谱裂解机理的角度出发对该药物中的4个未知的关键杂质的结构进行有效解析。此外,发现奥斯替尼及其个别杂质在质谱裂解过程中出现了显著的违背偶电子规则的碎片离子。通过对药物泰瑞沙的质谱分析期望能够提供一些分析、解析药物中未知杂质的思路和方法。     

Energy-dependent collision-induced dissociation study of buprenorphine and its synthetic precursors

The collision-induced dissociation (CID) of protonated buprenorphine ([M+H](+) ) and four related compounds was studied by electrospray quadrupole/time-of-flight mass spectrometry (ESI-QTOF MS). The fragmentation pathways were investigated by using energy-dependent CID and pseudo-MS(3) (in-source CID combined with tandem mass spectrometry (MS/MS)) methods. The first steps of the fragmentation are the parallel losses of the substituents from the non-aromatic ring moieties. Depending on the applied collision energies, a large number of further fragment ions arising from the cross-ring cleavages of the core-ring structure were observed. Based on the experimental results, a generalized fragmentation scheme was developed for the five buprenorphine derivatives highlighting the differences for the alternatively substituted compounds. The collision-energy-dependent fragmentation profile of buprenorphine is visualized in a two-dimensional plot to aid its fingerprint identification.     

Structural elucidation studies on 14- and 16-membered macrolide aglycones by accurate-mass electrospray sequential mass spectrometry

Collision induced dissociation sequential mass spectrometry was used to investigate the fragmentation of the heptaketide macrolide aglycones, 6-deoxyerythronolide B (6-dEB), erythronolide B (EB), and acetate-starter EB (Ac-EB). The fragmentations of two previously reported octaketide analogs produced by "stuttering" of the erythromycin polyketide synthase, stuttered-6-dEB and acetate-starter stuttered-6-dEB were also studied. The accuracy with which the mass of each fragment was measured allowed it to be attributed to an unambiguous formula. Most of the experiments were repeated using samples dissolved in deuterated solvents. These data were then used to deduce plausible fragmentation pathways of the five compounds which were shown to have a high degree of similarity. Preliminary fragmentation analysis of a novel octaketide analog was performed and the structure was predicted as stuttered EB. Subsequent scale-up of the bacterial fermentations, followed by isolation and characterization by nuclear magnetic resonance spectroscopy confirmed this prediction. Further fragmentation experiments were then performed on this compound, which provided further evidence of the similarity of the fragmentation schemes. These results demonstrate the utility of collision induced dissociation sequential mass spectrometry analysis in the preliminary screening of bacterial fermentations for new polyketides. These studies were performed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.     

Collision-induced dissociation of three groups of hydroxamate siderophores: ferrioxamines, ferrichromes and coprogens/fusigens

The behaviour of a series of hydroxamate siderophores--microbially produced iron complexes - was investigated using electrospray ionisation mass spectrometry (ESI-MS). Three groups of iron hydroxamate siderophores, namely the ferrioxamines, ferrichromes and coprogens/fusigens, were separated by high-performance liquid chromatography (HPLC) prior to ESI and MS(2) fragmentation. For the majority of the siderophores, both protonated molecules and sodium adducts were observed. The most abundant ion was selected for collision-induced fragmentation. Potential fragmentation mechanisms are postulated and discussed. Fragmentation patterns differed between siderophore groups; however, common fragmentation patterns were observed for siderophore ions within the groups examined. Cleavage frequently occurred at carbon-nitrogen or carbon-oxygen bonds. Fragmentation of the ions also involved cleavage of iron-oxygen bonds and transfer of the charge to iron.     

Mass-spectral behavior of nitrohydroxy- and nitromethoxymethylindoles

The principal pathways in the fragmentation of isomeric nitrohydroxy- and nitromethoxymethylindoles containing functional groups in the benzene ring were established by means of high-resolution mass spectrometry and deuterium labeling. The fragmentation of these compounds proceeds via different pathways as a function of the orientation of the functional substituants and the pyrrole nitrogen atom and differs from the fragmentation of other nitroarenes. The data obtained make it possible to reliably identify isomeric substances.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1070–1075, August, 1978.     

Fragmentation patterns of core-ionized thymine and 5-bromouracil

Photofragmentation of thymine and 5-bromouracil into cation and neutral fragments following the core ionization by soft x-rays using photoelectron-photoion-photoion coincidence technique has been studied. The fragment ion mass spectra were recorded in coincidence with the C 1s photoelectron spectra. In the case of thymine, deuterated samples were used to identify fragments. Deuteration or bromination allowed us to study not only the main fragmentation channels of these pyrimidine bases, but also to investigate if replacement of an exocyclic functional group affects molecular fragmentation. We found that the dominant fragmentation channels involve only one starting geometry, and the base ring and other bond cleavages, leading to the detected fragments, are essentially identical between thymine and 5-bromouracil. In addition, the relative intensities of the strongest fragmentation channels were determined and compared with calculated appearance energies using ab initio unrestricted Hartree-Fock theory.     

The investigation of substituent effects on the fragmentation pathways of pentacoordinated phenoxyspirophosphoranes by ESI‐MSn

The fragmentation pathways of pentacoordinated phenoxyspirophosphoranes were investigated in the positive mode by electrospray ionization multistage mass spectrometry. The results demonstrate that the sodium adducts of the title compounds undergo two competitive fragmentation pathways, and the fragmentation patterns are heavily dependent on the various substituent patterns at the phenolic group. An electron‐withdrawing substituent at the ortho‐position always results in the removal of a corresponding phenol analogue, while cleavage by spiroring opening becomes the predominant fragmentation pathway if an electron‐donating substituent is at the phenolic group. The substituent effects on the competitive fragmentation pathways were further elucidated by theoretical calculations, single crystal structure analysis, and high‐resolution mass spectrometry. The results contribute to the understanding of the gas‐phase fragmentation reactions and the structure identification of spirophosphorane analogues by electrospray ionization multistage mass spectrometry.     

Characterization of Progesterone Derivatives by LC-DAD-ESI/MSn and Its Application to the Identification of Impurities in Flurogestone Acetate

The fragmentation behaviors of progesterone derivatives were studied by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. Under tandem MS conditions, most of the fragments were formed by the cleavage of peripheral groups. Analyses of the fragmentation pathways revealed that the presence of substituents of a progesterone derivative could be deduced from characteristic losses. Characteristic cleavages of 28 and 58 Da were observed from ring cleavages with compounds containing two specific double bonds in the progesterone backbone. In addition, UV spectra were acquired to support MS-based analysis. The presence of nine impurities in crude flurogestone acetate samples were characterized, followed by their tentative assignments based on mass spectral fragmentation patterns.     

Mass spectra of 3(2H)-cinnolinone and 2-substituted derivatives

The mass spectrum of 3(2H)-cinnolinone indicates that it undergoes fragmentation in a fashion similar to other heterocyclic systems containing two vicinal nitrogens. The initial fragmentation, loss of CO, gives a 1H-indazole radical cation, as was shown by deuterium labelling and metastable ion spectra. Four 2-substituted-3(2H)-cinnolinones were also studied and it was found that their fragmentation patterns are highly influenced by the substituent groups.