2-氨基取代噻唑基膦酸脂的合成

本文报导一系列2-氨基-5-取代-4-噻唑基膦酸酯和2-氨基-4-取代-5-噻唑基膦酸酯的合成. 这类化合物显示了一定的杀菌活性.     

2-氨基取代噻唑基膦酸脂的合成

本文报导一系列2-氨基-5-取代-4-噻唑基膦酸酯和2-氨基-4-取代-5-噻唑基膦酸酯的合成. 这类化合物显示了一定的杀菌活性.     

2-氨基取代噻唑基膦酸酯的合成

许多噻唑类化合物具有生物活性,有些已作为杀菌剂、除草剂在农业上得到应用。近年来还进行了α-氨基酸的类似物α-氨基膦酸的合成及其生物活性的研究。迄今为止,还未见有4-噻唑基膦酸酯类化合物的合成和生物活性方面的文献报道。本文报道一系列2-氨基-5-取代-4-噻唑基膦酸酯(1)和2-氨基-4-取代-5-噻唑基膦酸酯(2)的合成。这类化合物显示了一定的杀菌活性。 1由取代乙酰氯与亚磷酸三酯经Arbuzov反应得到的取代乙酰基膦酸三酯(3)与缩二硫脲的溴氢酸盐(4)、一定量的弱碱(如硫脲、乙酸钾)在乙醇中反应制得。溶剂和碱的强弱     

α-(2-噻唑基脲基)膦酸二苯酯的合成

报道了一种简便的合成取代脲基膦酸酯的通用的新方法。在二氯甲烷中,三乙胺为缚酸剂的条件下,α-氨基膦酸二苯酯与三聚光气反应形成α-异氰酸基膦酸酯2,2不经分离,直接与2-氨基(苯并)噻唑加成得到α-(2-噻唑基脲基)膦酸二苯酯3,产率55.0%-88.9%。     

N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺的合成与抗肿瘤活性

采用衍生法,在N-[4-叔丁基-5-(4-氯苄基)噻唑-2-基]脂肪酰胺酰基的α-位,插入氨基,设计合成了N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺衍生物.以4,4-二甲基-1-芳基-3-戊酮为原料,经4-叔丁基-5-苄基-2-氨基噻唑(3),再经氯乙酰化和取代反应得21个N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺(1),其结构经~1H NMR、~(13)C NMR和元素分析确证.噻唑蓝(MTT)法体外抗肿瘤活性测试表明,该类新化合物对肺癌细胞(A549)、宫颈癌细胞(Hela)和乳腺癌细胞(MCF-7)具有抗肿瘤活性.其中N-[4-叔丁基-5-(胡椒基)噻唑-2-基]吗啉基乙酰胺(1t)对Hela细胞的抑制活性最好;对优选化合物1t进行了AO/EB双染和细胞周期实验,流式细胞仪分析表明,化合物1t可显著诱导肿瘤细胞凋亡,阻滞Hela细胞有丝分裂在S期.     

I_2/CuO催化的3-乙酰基香豆素和硫脲一锅反应合成3-(2-氨基-4-噻唑基)香豆素衍生物（英文）

香豆素和噻唑是两类具有广泛的生物活性和药理作用的杂环化合物,合成含噻唑基的香豆素衍生物在药物化学上具有重要的意义.本研究发展了一种方便高效地通过3-乙酰基香豆素和硫脲/N-取代硫脲在I_2/CuO催化作用下一锅反应合成3-(2-氨基)-4-噻唑基)香豆素衍生物的方法.所有目标化合物通过核磁共振、红外光谱、质谱分析证实.     

N-烷基/芳基-N′-(4-芳基噻唑-2-基)-N"-糖基胍的合成及生物活性研究

2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯(1)与2-氨基-4-取代苯基噻唑(2a～2b)反应,生成糖基硫脲衍生物3a～3b,再在伯胺存在下经氯化汞脱硫,得到一系列新的N-烷基/芳基-N′-(4-芳基噻唑-2-基)-N″-糖基胍类化合物(4a～4e,5a～5e).所有新化合物的结构均经IR,1H NMR,MS谱和元素分析证实,所得产物均为β-构型.生物活性测试结果表明,化合物4b和5d对HIV-1 PR表现出了较高的抑制活性.     

温和条件下[2-氨基-3-(苯并噻唑-2-基)-4H-色烯-4-基]膦酸酯衍生物的简便合成

含有不同取代基的(E)-2-(苯并噻唑-2-基)-3-(2-羟基苯基)丙烯腈与亚磷酸二苯酯在水中,无催化剂催化即可发生Michael加环/环化串联反应,可以高产率地生成相应的[2-氨基-3-(苯并噻唑-2-基)-4H-色烯-4-基]膦酸酯衍生物.同时,也尝试了水杨醛、2-(苯并噻唑-2-基)乙腈和亚磷酸二苯酯在Et_3N催化下的三组分一锅法反应合成相应的膦酸酯衍生物.     

I2/CuO催化的3-乙酰基香豆素和硫脲一锅反应合成3-(2-氨基-4-噻唑基)香豆素衍生物(英文)

香豆素和噻唑是两类具有广泛的生物活性和药理作用的杂环化合物,合成含噻唑基的香豆素衍生物在药物化学上具有重要的意义.本研究发展了一种方便高效地通过3-乙酰基香豆素和硫脲/N-取代硫脲在I₂/CuO催化作用下一锅反应合成3-(2-氨基)-4-噻唑基)香豆素衍生物的方法.所有目标化合物通过核磁共振、红外光谱、质谱分析证实.     

S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙酸硫酯类化合物脱除Boc保护基的反应研究

报道了取代苯丙酸类化合物1a～1d与N-叔丁氧羰基-L-半胱氨酸甲酯(2)在双(2-氧代-3-噁唑烷基)次磷酰氯(BOP-C1)作用下,以79%～92%收率得到缩合产物S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙酸硫酯类化合物3a～3d;3a～3d在三氟乙酸(TFA)作用下脱除Boc保护基时,结果不仅得到了正常的脱保护基产物4a～4d,还生成了2-取代噻唑啉类化合物5a～5d,研究表明5a～5d是由4a～4d分子内脱水环合而成.通过优化三氟乙酸用量、反应温度以及反应时间等条件,能够以较高收率分别得到4a～4d和5a～5d(收率85%～91%和86%～89%).而S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙烯酸硫酯类化合物3e～3f由于双键结构,在三氟乙酸作用下仅生成脱除Boc保护基产物4e～4f.该反应的研究为2-取代噻唑啉类化合物的合成提供了一种简便有效的方法.     

Electron impact-induced fragmentation of 2,1-benzisothiazoline 2,2-dioxide

The electron impact-induced fragmentation patterns of 2,1-benzisothiazoline 2,2-dioxide nitro derivatives were studied. The rationalizations proposed for the fragmentations are supported by accurate mass measurements, daughter ion (mass analysed ion kinetic energy and B/E linked-scan), parent ion, and constant neutral loss spectra in metastable and collision-induced dissociation modes and deuterium labelling.     

Mass spectrometric study of aliphatic alpha-carbonyl azides

A series of derivatives of 2-azidoacetic acid and 2-azidoacetone were synthesized and their behaviour under electron ionization conditions was investigated. This paper reports the electron ionization fragmentation mechanisms for five aliphatic alpha-carbonyl azides, which were clarified by accurate mass measurements and B/E linked scans. The substituent influences the abundance and the nature of the ions resulting from the molecular ion fragmentation.     

The electron impact induced fragmentation of 1,3-diphenyl-2-pyrazoline

The electron impact induced fragmentation of 1,3-diphenyl-2-pyrazoline was studied by nitrogen-15, carbon-13 and deuterium labelling, substitution in the para position of one of the phenyl rings by fluoro and methoxy groups, and ion kinetic energy spectroscopy, as well as accurate mass measurements. In the fragmentation pathway observed all the ions in the mass spectrum of 1,3-diphenyl-2-pyrazoline (except m/e 103) originate from the molecular ion, which in all compounds is the base peak. The formation of prominent fragment ions is discussed.     

Development of fast atom bombardment mass spectral methods for the identification of carcinogen-nucleoside adducts

An analytical strategy using fast atom bombardment (FAB) ionization and tandem mass spectrometry has been developed to determine the molecular weight and major fragment ions, and to provide limited structural characterization of low picomole levels of carcinogen-nucleoside adducts. This strategy consists of three main components: (1) the sensitivity for analysis by FAB combined with mass spectrometry is increased via chemical derivatization; (2) the nucleoside adducts are selectively detected by using constant neutral loss scans; and (3) structurally characteristic fragments are obtained by using daughter ion scans. Trimethylsilyl derivatized arylamine-nucleoside adducts have been detected at levels as low as a few picomoles by using this approach. After experimental determination of the mass of the BH ₂ ⁺ fragment ion, daughter ion spectra have been used to probe the structure specificity associated with collision-activated decomposition of this fragment. With model C-8 substituted arylamine adducts [N-(deoxyguanosin-8-yl)-4-aminobiphenyl, N-(deoxyadenosin--yl)-4-aminobiphenyl, and N-(deoxyguanosin-8-yl)-2-aminofluorene], nucleoside-specific and carcinogen-specific fragmentation have been observed in daughter ion spectra.     

Mass spectrometry of heterocyclic compounds—III. Electron-impact-induced fragmentation of 1,2-benzisothiazole and some 3-substituted derivatives

The mass spectra of fifteen 1,2-benzisothiazoles are reported; their fragmentation patterns have been investigated by labelling experiments, high resolution mass measurements and defocused metastable ion detection. The parent compound of the series, 1,2-benzisothiazole, eliminates HCN after partial inter-ring hydrogen scrambling. The extent of scrambling has been determined for normal daughter ions produced at different electron beam energies and also for metastable daughter ions, and is compared with the data reported for benzothiazole. Some 3-substituted derivatives show unusual fragmentation patterns. The mechanisms of these processes are under further investigation.     

Mass spectrometry of trialkylsilyl and acyl derivatives of 2′-deoxynucleosides

The electron impact mass spectra of monosilyl and mixed acyl-silyl derivatives of 2′-deoxynucleosides are described in detail. (Silyl = tert-butyldimethylsilyl, cyclo-tetramethylene-isopropylsilyl, or cyclo-tetramethylene-tert-butylsilyl; acyl = acetyl or trifluoroacetyl.) The interpretation of the fragmentation pathways was aided by metastable ion decomposition studies, precise mass and deuterium labelling measurements. Mass spectrally, the acyl substituents are mostly ‘passive’ and have (with possibly one exception) little fragmentation directing capability. In contrast, the silyl groups have powerful fragmentation directing properties. Elimination of the bulky alkyl radical R^˙ (tert-butyl or isopropyl) from the molecular ion produces the siliconium ion, [M–R]⁺, which is the precursor for most of the other prominent ions in the spectra. These arise from ‘siliconium ion rearrangements’ resulting from the interaction of the positively charged siliconium ion centre with the electron dense regions (i.e. oxygens) in the molecule, to form cyclic silyloxonium ions which subsequently decompose. Since the interacting oxygen and silicon must be sterically accessible, the fragment ion types and their abundances are very dependent upon structure. Consequently, [M–R]⁺ ions formed from 3′- or 5′-O-silyl groups give rise to different sets of daughter ions which, for the most part, are not found, or have very low abundances, in the mass spectra of underivatized or trimethylsilylated nucleosides. Detailed information on sugar and base moieties and isomeric substitution is readily obtained.     

Fast atom bombardment mass spectra of isobaric/isomeric phosphonium salts

The positive ion fast atom bombardment mass spectra of isobaric/isomeric aryl phosphonium salts typically contain abundant intact cations, which can be used to establish the cationic molecular weight, characteristic ions that can be used to delineate structural subgroups, and fragment ions corresponding to losses of small neutral molecules. Several of the fragmentation pathways were elucidated by parent ion and daughter ion tandem mass spectrometry experiments. Dependence of the fragmentation reactions on functional group substitution suggests that fast atom bombardment mass spectrometry is an excellent method for the differentiation of isobaric/isomeric phosphonium salts used in synthetic organic and industrial catalytic processes.     

Mass spectra of sterically crowded trialkylsilyl derivatives of nucleosides

The electron impact mass spectra of tert-butyldimethylsilyl-, cyclo-tetramethylene-tert-butylsilyl and cyclo-tetramethylene-isopropylsilyl- ether derivatives of ribo- and 2′-deoxyribonucleosides are described in detail. The interpretation of fragmentation pathways of full and mixed derivatives was aided by metastable ion decomposition studies, precise mass and deuterium labelling measurements, and spectra of mixed derivatives containing the ‘passive’ (in these spectra) trimethylsilyl group. The sterically crowded silyl groups have a powerful fragmentation directing effect. Elimination of a bulky radical, R˙ (tert-butyl or isopropyl), from the molecular ion produces the siliconium ion [M? R]⁺, which is the precursor for most of the other prominent ions in the spectra. These arise from ‘siliconium ion rearrangements’ resulting from the interaction of the positively charged siliconium ion center with electron dense regions (i.e. oxygens) in the molecule, to form cyclic silyloxonium ions which subsequently decompose. Since the interacting oxygen and silicon must be sterically accessible, the fragment ion types and their abundances are very dependent upon structure. Consequently, [M? R]⁺ ions formed from 2′, 3′ or 5′-O-silyl groups give rise to different sets of daughter ions which, for the most part, are not found, or have very low abundances, in the mass spectra of underivatized or trimethylsilylated nucleosides. Detailed information on sugar and base moieties and isomeric substitution is readily obtained.     

Mass spectrometric investigation of buspirone drug in comparison with thermal analyses and MO-calculations

The buspirone drug is usually present as hydrochloride form of general formula C(21)H(31)N(5)O(2).HCl, and of molecular weight (MW)=421.96. It is an analgesic anxiolytic drug, which does not cause sedative or depression of central nervous system. In the present work it is investigated using electron impact mass spectral (EI-MS) fragmentation at 70 eV, in comparison with thermal analyses (TA) measurements (TG/DTG and DTA) and molecular orbital calculation (MOC). Semi-empirical MO calculation, PM3 procedure, has been carried out on buspirone both as neutral molecule (in TA) and the corresponding positively charged species (in MS). The calculated MOC parameters include bond length, bond order, particle charge distribution on different atoms and heats of formation. The fragmentation pathways of buspirone in EI-MS lead to the formation of important primary and secondary fragment ions. The mechanism of formation of some important daughter ions can be illuminated from comparing with that obtained using electrospray ESIMS/MS mode mass spectrometer through the accurate mass measurement determination. The losses of the intermediate aliphatic part (CH2)4 due to cleavage of N-C bond from both sides is the primary cleavage in both techniques (MS and TA). The PM3 provides a base for fine distinction among sites of initial bond cleavage and subsequent fragmentation of drug molecule in both TA and MS techniques; consequently the choice of the correct pathway of such fragmentation knowing this structural session of bonds can be used to decide the active sites of this drug responsible for its chemical, biological and medical reactivity.     

Evidence for an aryl migration during the electron impact induced fragmentation of substituted aryloxymethylquinoxalines.

The electron impact (EI) mass spectra of 34 differently substituted 2-phenoxymethyl-, 2-naphthyloxymethyl-, 2-pyridinyloxymethyl- and 2-chinolinyloxymethylquinoxalines were recorded. The fragmentation patterns were examined by metastable ion analysis and exact mass measurements, employing finally also selective deuterium labelling. The inclusion of the substituted aryl ring moiety appears to be important for the fragmentation of the aryloxymethylquinoxalines. A molecular ion rearrangement is proposed for the observed loss of OH* and CHO* radicals. The influence of the different substituents on the aryl ring moiety on the rearrangement in the gas phase and on the resulting fragmentation was investigated.