ω-氯氟烷基醇,烯烃及环氧化物的合成

全氟烷基碘的加成反应一直活跃在氟化学中,即使近来也依然受到注意,这是因为由它们出发可做许多有用的中间体,其中氟烷基取代的醇可做织物表面处理剂,氟烷基取代的环氧化合物可做润滑剂。我们曾用引发剂,使ψ—碘代全氟烷基磺酰氟与多键类化合物在较温和条件下进行加成。黄维垣教授等用NaHCO_3—K_3[Fe(CN)_6]引发Cl(CF_2)_(4.6)I与烯丙醇顺利加成。     

Design,synthesis, and anti-TMV bioactivities of nucleobase phosphonate analogs

A series of novel nucleobase derivatives and their analogues possessing diethoxyphosphoryl scaffolds were synthesized through four-step reactions and screened for their antiviral activity toward tobacco mosaic virus (TMV). Preliminary bioassays suggested that some of these simple structures displayed appreciable anti-TMV activity in vivo. Among them, compound (diethoxyphosphoryl)methyl 4-[2-(1H-benzo[d][1,2,3]triazol-1-yl)acetamido]-benzoate (a-3) exerted the strongest chemotherapeutic and protective effects against TMV with the rates of 52.8 and 72.2% at the dosage of 500 µg/mL, respectively, which were comparable with those of the commercial agricultural antiviral agent ningnanmycin (54.2 and 70.2%). Molecular docking with TMV helicases revealed that compound a-3 had strong interactions with receptor amino acid residues. Given the facile synthetic route and significant chemotherapeutic and protective potentials, compound a-3 could be further studied and exploited as a promising antiviral candidate.     

Synthesis and antibacterial activity of Schiff bases of 5-substituted isatins

Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using spectroscopic methods such as NMR, IR and mass spectrometry. Furthermore, Nbenzylation of isatin followed by the Schiff base formation furnished a new series of compounds(11a–13c) which allowed the analysis of the effect of isatin N-substitution on the bioactivity of the resulting compounds. The antibacterial activity of the synthesized derivatives was evaluated using a microtiter plate method on a series of gram positive and gram negative bacterial strains. Compounds 2d, 3b, 5c and 6a were among the most potent derivatives against Pseudomonas aeruginosa(MIC = 6.25 μg/m L).Analysis of the structure–activity relationship showed that the incorporation of(thio)urea-based Schiff bases lead to more potent derivatives with a broader spectrum of antibacterial activity. In addition,highly lipophilic compounds such as 11a–12c did not show any measurable antibacterial activity, which implies that an optimal lipophilicity might be an important requirement for the antibacterial activity of the studied isatins. Finally, the finding that hydantoin derivatives of N-benzylisatins(13a–13c) still exhibit some antibacterial activity prompted us to consider exploring the bioactivity of more diverse derivatives of isatin-aminohydantoin Schiff bases(compounds 1a–1d) in our future studies.     

20(S)-20-O-Camptothecin β-Aminopropionate: Novel Synthesis and Antitumor Activity in vitro

To improve the biological anticancer activity of 20(S)-camptothecin, a novel class of 20(S)-20-O-camptothecin β-aminopropionates were designed and synthesized with camptothecins as the starting materials, through acylation with acryloyl chloride followed by Michael′s addition. Twelve esters, 1a-1d, 4a-4d and 5a-5d, were synthesized and evaluated by using MTT assay method. The results demonstrate that all these compounds show a potential cytotoxicity on KB, HT-29, HCT-8, and Bel7402 tumor cell lines. Some compounds, 1d, 4c, 5b, 5c and 5d, show a higher cytoto-xicity on KB and HCT-8 compared with camptothecin.     

Lithium fluoroarylamidinates: syntheses, structures, and reactions

Lithium fluoroarylamidinates [(Ar(F)C(NSiMe(3))(2)Li)(n).xD] (Ar(F) = 4-CF(3)C(6)H(4), n = 2, D = OEt(2), x = 1 (2a); n = 1, D = TMEDA, x = 1 (4a); Ar(F) = 2-FC(6)H(4), n = 2, D = OEt(2), x = 1 (2b); Ar(F) = 4-FC(6)H(4), n = 2, D = OEt(2), x = 2 (2c); Ar(F) = 2,6-F(2)C(6)H(3), n = 2, D = OEt(2), x = 1 (2d); n = 2, D = 2,6-F(2)C(6)H(3)CN, x = 2 (3d); Ar(F) = C(6)F(5), n= 2, D = OEt(2), x = 1 (2e), n = 1, D = TMEDA, x = 1 (4e); n = 1, x = 2, D = OEt(2) (5e); D = THF (6e)) were prepared by the well-known method from LiN(SiMe(3))(2) and the corresponding nitrile in diethyl ether or by addition of the appropriate donor D to the respective diethyl ether complexes. Depending on the substituents at the aryl group and on the donors D, three different types of structures were confirmed by X-ray crystallography. Hydrolysis of 2e gave C(6)F(5)C(NSiMe(3))N(H)SiMe(3) (7e) and C(6)F(5)C(NH)N(H)SiMe(3) (8e). The lithium fluoroarylamidinates 2a-2d react with Me(3)SiCl to give the corresponding tris(trimethylsilyl)fluoroarylamidines Ar(F)C(NSiMe(3))N(SiMe(3))(2) (9a-9d). Attempts to prepare C(6)F(5)C(NSiMe(3))N(SiMe(3))(2) from 2e and Me(3)SiCl failed; however, the unprecedented cage [[C(6)F(5)C(NSiMe(3))(2)Li](4)LiF] (10e) in which a fluoride center is surrounded by a distorted trigonal bipyramid of five Li atoms was obtained from this reaction.     

Synthesis and characterization of six-arm star-shaped liquid crystalline cyclotriphosphazenes

<正>The synthesis and mesomorphic properties of a new class of liquid crystalline cyclotriphosphazenes with rigid cyanostilbene groups and flexible alkoxy groups are reported.The thermal behaviors of cyclotriphosphazene derivatives 5a-5d are studied by the means of differential scanning calorimetry,polarizing optical microscopy.Nematic phases were observed in compounds 5a-5d both on heating and cooling.The clear temperatures of compounds 5a-5d slightly increased with increasing length of terminal alkyl chain.Compounds 5a-5d showed different mesogenic region from minimum 5℃to maximum 142℃.     

Isostructural potassium and thallium salts of sterically crowded triazenes: a structural and computational study

Because of their similar cationic radii, potassium and thallium(I) compounds are usually regarded as closely related. Homologous molecular species containing either K(+) or Tl(+) are very rare, however. We have synthesized potassium and thallium salts MN3RR' derived from the biphenyl- or terphenyl-substituted triazenes Tph2N3H (1a), Dmp(Mph)N3H (1b), Dmp(Tph)N3H (1c), and (Me4Ter)2N3H (1d) (Dmp=2,6-Mes 2C6H3 with Mes=2,4,6-Me3C6H2; Me4Ter=2,6-(3,5-Me2C6H3)2C6H3; Mph=2-MesC6H4; Tph=2-TripC6H4 with Trip=2,4,6-(i)Pr3C6H2). The potassium complexes 2a- d were obtained in almost quantitative yield from the reaction of 1a- d with potassium metal in n-heptane. Metalation of 1a- d with TlOEt afforded the thallium triazenides 3a- d in high yields. All new compounds have been characterized by (1)H and (13)C NMR spectroscopy, elemental analysis, and X-ray crystallography and for selected species by melting point (not 3b), IR spectroscopy (2a, 2d, 3a, 3c, 3d), and mass spectrometry (2a, 3c). In the solid-state structures of monomeric 2a and 3a, quasi-monomeric 2b, 3b, 2c, and 3c, and dimeric 2d and 3d additional metal-eta (n)-pi-arene-interactions to the flanking arms of the biphenyl- and terphenyl groups in the triazenide ligands of decreasing hapticity n are observed. Remarkably, all homologous potassium and thallium complexes crystallize in isomorphous cells. For 2a and 3a, the nature of the M-N and M...C(arene) bonding was studied by density functional theory calculations.     

Synthesis, characterization, biocide and toxicological activities of di-n-butyl- and diphenyl-tin(IV)-salicyliden-beta-amino alcohol derivatives

The one pot reaction of salicylaldehyde 1, beta-amino alcohols 2a-2c, and di-n-butyltin(IV) oxide 3a or diphenyltin(IV) oxide 3b produced five diorganotin(IV) compounds, 4a-4c, 5a, and 5c, in good yields. All compounds were characterized by IR, (1)H, (13)C, and (119)Sn NMR spectroscopy, and elemental analysis; furthermore, compounds 4b, 4c, 5a, and 5c were characterized by X-ray diffraction analysis. After the structural characterization, all of the compounds were tested in vitro against Bacillus subtilis (Gram-positive, strain ATCC 6633), Escherichia coli (Gram-negative, strain DH5alpha), Pseudomonas aeruginosa (Gram-negative, strain BH3), Desulfovibrio longus (strain DSM 6739), and Desulfomicrobium aspheronum (strain DSM 5918) to assess their antimicrobial activity. Compounds 4 and 5 demonstrated a wide range of bactericidal activities against the tested aerobic (one Gram-positive and two Gram-negative subtypes) and anaerobic bacteria (two sulfate-reducing bacteria, SRB). Compound 5 had better bactericidal performances than compound 4. For all of the compounds, the acute toxicity was measured using luminescent bacteria toxicity (LBT-Microtox) tests to track their further environmental impact. According to these results and in order to fulfill environmental regulations, the toxicity of the compounds studied herein can be modulated through the proper selection of the disubstituted tin(IV) moiety.     

Design,synthesis and biological evaluation of new rhodacyanine analogues as potential antitumor agents

In an attempt to develop potent antitumor agents,new rhodacyanine analogues containing the pyridinium ring（5a-5h）,the isoquinolinium ring（6a-6c） and the quinolinium ring（7a-7e） linked to the rhodanine ring via N-N covalent bond were designed, synthesized and evaluated for antitumor activity against human lung cancer cell line（H460） by MTT assay in vitro.Most of the tested compounds showed enhanced antitumor activity with IC₅₀ values ranging from 0.006 to 9.2 u,mol/L as compared to the lead compound MKT-077.Among them,the most promising compound 7d(IC₅₀ = 0.006μmol/L) was 216.7 times more active than MKT-077(IC₅₀ = 1.3μmol/L).The preliminary structure-activity relationship of the target compounds was discussed.     

Synthesis, antibacterial, antifungal and antiviral activity evaluation of some new bis-Schiff bases of isatin and their derivatives

Twelve new bis-Schiff bases of isatin, benzylisatin and 5-fluoroisatin 3a-3l were prepared by condensation of isatin, benzylisatin and 5-fluoroisatin with primary aromatic amines. The chemical structures of the products were confirmed by 1H- and 13CNMR, IR and mass spectral data. The compounds were screened for antiviral activity against a panel of DNA and RNA viruses. Minimum cytotoxic and minimum virus-inhibitory concentrations of these compounds were determined. Compounds 3c and 3i were the most cytotoxic in HEL cells. These newly synthesized bis-Schiff bases were also tested for their antibacterial and antifungal activities. They did not display activity against S. cerevisiae (ATCC 28383) or C. albicans (CIP 1180-79).     

The antioxidant profile of 2,3-dihydrobenzo[b]furan-5-ol and its 1-thio, 1-seleno, and 1-telluro analogues

A novel synthesis of 2,3-dihydrobenzo[b]thiophene-5-ol based on intramolecular homolytic substitution on sulfur was reported. The "antioxidant profile" of the series of 2,3-dihydrobenzo[b]furan-5-ol (2a) its 1-thio (2b), 1-seleno (2c) and 1-telluro (2d) analogues was determined by studies of redox properties, the capacity to inhibit stimulated lipid peroxidation, the reactivity toward tert-butoxyl radicals, the ability to catalyze decomposition of hydrogen peroxide in the presence of glutathione, and the inhibiting effect on stimulated peroxidation in liver microsomes. The one-electron reduction potentials of the aroxyl radicals corresponding to compounds 2a-2d, E degrees (ArO(*)/ArO(-)) were 0.49, 0.49, 0.49, and 0.52 V vs NHE, respectively, as determined by pulse radiolysis. With increasing chalcogen substitution the compounds become slightly more acidic (pK(a) = 10.6, 10.0, 9.9, and 9.5, respectively, for compounds 2a-2d). By using Hess' law, the homolytic O-H bond dissociation enthalpies of compounds 2a-2d (340, 337, 336, and 337 kJ mol(-)(1), respectively) were calculated. The reduction potentials for the proton coupled oxidation of compounds 2a-2d (ArOH --> ArO(*) + H(+)) as determined by cyclic voltammetry in acetonitrile were 1.35 (irreversible), 1.35 (quasireversible) 1.13 (reversible), and 0.74 (reversible) V vs NHE, respectively. As judged by the inhibited rates of peroxidation, R(inh), in a water/chlorobenzene two-phase lipid peroxidation system containing N-acetylcysteine as a thiol-reducing agent in the aqueous phase, the antioxidant capacity increases (2d > 2c = 2b > 2a) as one traverses the group of chalcogens. Whereas the times of inhibition, T(inh), were slightly reduced for the oxygen (2a) and sulfur (2b) derivatives in the absence of the thiol-reducing agent, they were drastically reduced for the selenium (2c) and tellurium (2d) derivatives. This seems to indicate that the organochalcogen compounds are continuously regenerated at the lipid aqueous interphase and that regeneration is much more efficient for the selenium and tellurium compounds. The absolute rate constants for the oxidation of compounds 2a-2b by the tert-butoxyl radical in acetonitrile/di-tert-butyl peroxide (10/1) were the same-2 x 10(8) M(-)(1) s(-)(1). Whereas the oxygen, sulfur, and selenium derivatives 2a-2c were essentially void of any glutathione peroxidase-like activity, the organotellurium compound 2d accelerated the initial reduction of hydrogen peroxide, tert-butyl hydroperoxide, and cumene hydroperoxide in the presence of glutathione 100, 333, and 213 times, respectively, as compared to the spontaneous reaction. Compounds 2a-2d were assessed for their capacity to inhibit lipid peroxidation in liver microsomes stimulated by Fe(II)/ADP/ascorbate. Whereas the oxygen, sulfur, and selenium compounds showed weak inhibiting activity (IC(50) values of approximately 250, 25, and 13 microM, respectively), the organotellurium compound 2d was a potent inhibitor with an IC(50) value of 0.13 microM.     

Diastereoselective synthesis of cyclosaligenyl-nucleosyl-phosphotriesters

A diastereoselective synthesis of cycloSal-phosphotriesters (cycloSal=cycloSaligenyl) based on chiral auxiliaries has been developed that allows the synthesis of single diastereomers of the cycloSal-pronucleotides. In previously described synthesis routes, the cycloSal-compounds were always obtained as 1:1 diastereomeric mixtures that could be separated in only rare cases. However, it was shown that the diastereomers have different antiviral activity, toxicity, and hydrolysis stabilities. Here, first a chiral thiazoline derivative was used to prepare nonsubstituted and 5-methyl-cycloSal-phosphotriesters in 48 and ≥95% de (de=diastereomeric excess). However, this approach failed to give the important group of 3-substituted cycloSal-nucleotides. Therefore, two other chiral groups were discovered that allowed the synthesis of (R(P))- and (S(P))-3-methyl-cycloSal-phosphotriesters as well. The antiviral activity was found to be five- to 20-fold different between the two individual diastereomers, which proved the importance of this approach.     

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC₅₀ = 45.3 µM), Ebola pseudotype viruses (IC₅₀ = 0.12 µM), and authentic EBOV (IC₅₀ = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC₅₀ = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.     

Synthesis and in vitro anti-human cytomegalovirus (hcmv) activity of certain alkenyl substituted cytosines and 5-halocytosines

The 1-[(Z)-2-penten-1-yl] and 1-(3-methyl-2-buten-1-yl) derivatives of cytosine, 5-bromocytosine, 5-fluorocytosine, and 5-iodocytosine were prepared by a reaction of the sodium salt of the requisite cytosine with (Z)-1-bromo-2-pentene and 4-bromo-2-methyl-2-butene, respectively. The eight alkenylcytosines 5a-5h were evaluated in cell culture for their anti-HCMV activity. Only the derivatives of 5-bromocytosine, 5c and 5d , showed slight activity in this assay.     

The synthesis of substituted [1]benzothieno[2,3-c]quinolines and their N-methyl quaternary salts

Four substituted [1]benzothieno[2,3-c]quinolines 14a-14d were prepared by photocyclization of the appropriate carboxamides 8a-8d to the corresponding [1]benzothieno[2,3-c]quinolin-6(5H)-ones 12a-12d followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 13a-13d and dechlorination resulting in the title compounds. Treatment of 14a-14d with iodomethane furnished the corresponding N-methyl quaternary salts 5a-5d .     

6-取代氨基-2-烷硫基腺苷化合物的合成及抗血小板凝聚活性

以鸟苷(1)为原料, 经过糖环保护得到2',3',5'-三-O-乙酰基鸟嘌呤核苷(2), 化合物2与三氯氧磷反应得到2-氨基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(3), 化合物3经重氮化后再与二烷基二硫醚反应得到2-烷硫基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(4a~4d), 化合物4a~4d与胺进行亲核取代反应后, 脱去糖环保护得到12个新型的6-取代氨基-2-烷硫基腺苷化合物(5a~5l). 采用¹H NMR, ¹³C NMR, IR和高分辨质谱(HRMS)对目标化合物的结构进行了确证, 并对所有化合物进行了体外抗血小板聚集活性测试. 结果表明, 当测试浓度为10 μmol/L时, 化合物5a~5l仍具有一定的抗凝活性, 其中, 6-(3-苯基丙基)氨基-2-丙硫基腺苷(5d)活性最为显著, 抑制率可达90.2%.     

新型吲唑-查尔酮杂合物的合成及抗肿瘤活性

设计并合成了一系列新型含查尔酮-吲唑杂合衍生物,并对其体外肿瘤活性进行初步研究。 先以2,6-二氟苯腈和吗啉为起始原料,经过取代和环合两步反应合成4-吗啉-3-氨基-1H-吲唑。 4-吗啉-3-氨基-1H-吲唑与含羧基的查尔酮中间体与经过酰胺化反应制备了9个新型含查尔酮-吲唑杂合衍生物,其结构经傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(NMR)、质谱(MS)和元素分析确证。 采用MTT法,以索拉菲尼为阳性对照药,以人胃癌细胞株(MKN45)和人肺癌细胞株(A549)为测试细胞株对目标化合物进行抗肿瘤活性评价。 结果表明,大部分目标化合物显示了较好的抗肿瘤活性,其中化合物4a和4d活性较好,其抑制人胃癌细胞株MKN45的IC₅₀分别为2.65和3.55 μmol/L,均优于阳性对照药索拉菲尼(IC₅₀=4.69 μmol/L)。     

Isolation and structural determination of new sphingolipids and pharmacological activity of africanene and other metabolites from Sinularia leptoclados.

Two new sphingolipids, (2S,3S,4R)-1,3,4-trihydroxy-2-[((R)-2'-hydroxytetradecanoyl) amino] tricosane (4) and (2S,3S,4R)-1,3,4-triacetoxy-2-[((R)-2'-acetoxyoctadecanoyl) amino]octadecane (5) along with africanene (1, reasonably good yield), 23-demethylgargosterol (2) and batylalcohol (3) have been isolated from the soft coral Sinularia leptoclados. Preliminary studies for pharmacological activity (blind screening and toxicity studies) of africanene were conducted. Africanene exhibited in vitro and in vivo cytotoxicity, dose dependent hypotensive activity as well as antiinflammatory activity. The pharmacological and toxicity studies on africanene are being reported for the first time and findings strongly encourage further investigation. Compounds 1, 4 and 5 were studied for the antibacterial, antifungal and antiviral activity while compounds 4 and 5 were also studied for the short term in vitro cytotoxic activity.     

Structural and photophysical studies of trans-AB(2)C-substituted porphyrin ligands and their zinc and copper complexes

trans-AB(2)C porphyrins with A = C(6)H(4)-COOR, C = C(6)H(4)-NX(2) and B = C(6)H(5) (R = CH(3), H; X = O, H) have been synthesised by a rational high-yield procedure (1a-1d) and their zinc(ii) and copper(ii) complexes have been prepared (2a-2d, 3a-3d ).1a, 2a .THF and 3a display different distortions of the porphyrin core as shown by single crystal X-ray crystallography and NSD analyses. The Soret and Q bands of free-base and metalated porphyrins with mixed electron donating and withdrawing substituents (NH(2)/COOR) are red-shifted as are the corresponding emission bands of free-base and zinc porphyrins. The electronic asymmetry revealed by spectrocopy is rationalised by DFT calculations.