Syntheses of thallusin analogues and their algal morphogenesis-inducing activities

Thallusin is the only known natural product that induces cell differentiation followed by formation of a thallus during the growth of green macroalgae such as Monostroma and Ulva. Herein, various thallusin analogues based on the terpen skeleton were synthesized to study the structure?activity relationships of thallusin. The potency of the synthetic analogues was investigated in an experimental assay, which demonstrated that the 19-methyl group in thallusin is essential for potent morphogenesis-inducing activity.     

Syntheses of glucose-containing E5564 analogues and their LPS-antagonistic activities

Lipid A analogues containing a glucose moiety on their non-reducing end were synthesized, and their LPS-antagonistic activities were measured. The inhibitory activities (IC₅₀) on LPS-induced TNFα production of these six compounds, 26, 33, 44β, 52β, 59, and 61, toward human whole blood cells were 0.49, 0.65, 0.51, 0.98, 0.46, and 1.11 nM, respectively. Inhibitory doses (ID₅₀) of compounds 26, 33, 44β, 59, and 61 on TNFα production induced by coinjection of galactosamine and LPS in C3H/HeN mice were measured. The ID₅₀ values of these compounds were 0.45, 0.96, <0.2, 1.08, and <0.2 mg/kg, respectively. Moreover, C3H/HeN mice preinjected with compounds 26, 33, and 44β were protected from lethality induced by coinjection of galactosamine and LPS. Out of eight mice preinjected with 1 mg/kg of compounds 26, 33, and 44β, five, eight and six mice were protected, respectively.     

Syntheses and biological activities of renin inhibitors containing statine analogues

Syntheses and biological activities of dipeptide renin inhibitors that contain statine analogues are described. The key steps of the synthetic approach to dipeptide renin inhibitors are the asymmetric synthesis of 2(R)-substituted-3-aminocarbonylpropionic acids and the diastereoselective syntheses of (3S,4S)-statine analogues. These inhibitors (2,14-40) inhibited human renin in the 3-140 nM range. Inhibitor ES 6864 (2) was found to be a highly potent inhibitor of human renin (IC50: 4.6 x 10(-9) M) and showed high enzyme specificity. Oral administration of ES 6864 at 3 mg/kg to conscious, sodium-depleted marmosets inhibited plasma renin activity (PRA) more than 80% after 1 h.     

Syntheses and antitumor and anti-aids activities of polymers containing pyrimidine derivative

The new monomer, 5'-O-methacryloyl-3'-azido-3'-deoxy-thymidine (MAZT), was synthesized from methacryloyl chloride (MAC) and 3'-azido-3'-deoxythymidine (AZT). Poly(MAZT), poly(MAZT-co-AA) and terpoly(MAZT-FUR-MAH) were synthesized by radical polymerizations. The average molecular weights of synthesized polymers were in the range of 8,800 ∼23,000 depending on polymers. The in vivo antitumor activities of polymers at 800mg/kg were increased in the following order: terpoly(MAZT-FUR-MAH) >x poly(MAZT-co-AA) > poly(MAZT) > AZT > 5-FU. The in vitro anti-HIV activities of synthesized polymers were less effective than those of AZT and D4T. But the cytotoxicities of the polymers on the MT-4 cell line were found to be much less toxic than AZT.     

Syntheses and antitumor activities of medium molecular weight polymers containing 5-fluorouracil

The new monomer α-ethoxy-3,6-endo-methylene-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil (EMTFU) was synthesized from 5-fluorouracil (5-FU) and α-ethoxy-3,6-endo-methylene-1,2,3,6-tetrahydrophthaloyl chloride (EMTC). Poly(α-ethoxy-3,6-endomethylene-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(EMTFU)], poly(α-ethoxy-3,6-endo-methylene-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil-co-acrylic acid) [poly(EMTFU-co-AA)], and poly(α-ethoxy-3,6-endomethylene-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil-co-vinyl acetate) [poly(EMTFU-co-VAc)] were synthesized by photopolymerizations using 2,2-dimethoxy-2-phenylacetophenone (DMP) as the photoinitiator. The synthesized EMTFU and its polymers were identified by Fourier transfer infrared (FT-IR), ¹H nuclear magnetic resonance (NMR), and ¹³C-NMR spectroscopies. The contents of EMTFU in poly(EMTFU-co-AA) and poly(EMTFU-co-VAc) determined by elemental analysis were 46 and 70 mol %, respectively. The number average molecular weights of the synthesized polymers determined by gel permeation chromatography (GPC) were in range of 17,200–20,900. The in vitro cytotoxicities of samples were evaluated with mouse mammary carcinoma (FM3A), mouse leukemia (P388), and human histiocytic lymphoma (U937) as cancer cell lines and AC2F as a normal cell line. The cytotoxicities of 5-FU and synthesized samples against cancer cell lines increased in following orders: 5-FU ≈ EMTFU > poly(EMTFU-co-AA) > poly(EMTFU) > poly(EMTFU-co-VAc). The in vivo antitumor activities of the synthesized samples against mice bearing the sarcoma 180 tumor cell line were evaluated. The in vivo antitumor activities of EMTFU and its polymers were greater than those of 5-FU at a dosage of 80 mg/kg. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2985–2992, 1998     

Synthesis, crystal structures and in vitro antitumor activities of some arylantimony derivatives of analogues of demethylcantharimide

A series of novel arylantimony derivatives of analogues of demethylcantharimide with the formulae Ar_nSbL_(5−n) and Ar_nSbL^′_(5−n)(LH=N-hydroxy-demethyldehydrogencantharimide, L^′H=N-hydroxy-demethylcantharimide, n=3, 4; ArC₆H₅, 4-CH₃C₆H₄, 3-CH₃C₆H₄, 2-CH₃C₆H₄, 4-ClC₆H₄, 4-FC₆H₄) were synthesized and characterized by elemental analysis, IR, ¹H NMR and mass spectroscopy. The crystal structures of (C₆H₅)₄SbL, (4-CH₃C₆H₄)₃SbL₂ and (3-CH₃C₆H₄)₃SbL^′₂ were determined by X-ray diffraction. The in vitro antitumor activities of all compounds against six cancer cells are reported.     

Syntheses,electrochemical studies and crystal structures of new unsymmetrical tetrathiafulvalene carboxylate derivatives

A series of new unsymmetrical tetrathiafulvalene carboxylate derivatives ( 7‐11 ) were synthesized and characterized by NMR, MS, electrochemical studies and X‐ray crystal structural determination. Compound 8 showed obvious changes in redox peak potentials as the concentration of p‐toluenesulfonic acid changes.     

Syntheses and antitumor activities of polymers containing amino acid and 5‐fluorouracil moieties

The new monomer, 3,6‐endo‐methylene‐1,2,3,6‐tetrahydrophthalimidoethanoyl‐5‐fluorouracil (ETEFU), was synthesized from 5‐fluorouracil (5‐FU) and 3,6‐endo‐methylene‐1,2,3,6‐tetrahydophthalimidoethanoyl chloride (ETEC). Its homopolymer and copolymers with acrylic acid (AA) and vinyl acetate (VAc) were prepared by photopolymerization reactions using 2,2‐dimethoxy‐2‐phenylacetophenone (DMP) as the photoinitiator. The synthesized ETEFU and polymers were identified by FT‐IR, ¹H‐NMR, and ¹³C‐NMR spectra. The contents of ETEFU units in poly(ETEFU‐co‐AA) and poly(ETEFU‐co‐VAc) were 20 and 17 mol%, respectively. The number‐average molecular weights of the synthesized polymers determined by gel permeation chromatography (GPC) were 4,600 to 10,700 g mol⁻¹. In vitro cytotoxicities of samples were evaluated with cancer cell lines [mouse mammary carcinoma (FM3A), mouse leukemia (P388), and human histiocytic lymphoma (U937)] and a normal cell line [mouse liver cells (AC2F)]. Cytotoxicities of 5‐FU and synthesized samples against the cancer cell lines were ranked as follows: ETEFU > poly(ETEFU) > 5‐FU > poly(ETEFU‐co‐AA) > poly(ETEFU‐co‐VAc). The in vivo antitumor activities of poly(ETEFU) and poly(ETEFU‐co‐AA) against Balb/C mice bearing the sarcoma 180 tumor cells were greater than those of 5‐FU at all doses except for the activity of poly(ETEFU) at 0.8 mg/kg. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1589–1595, 1999     

Macrocyclic organotin(IV) carboxylates based on benzenedicarboxylic acid derivatives: Syntheses, crystal structures and antitumor activities

Six new organotin carboxylates based on 1,3-benzenedicarboxylic acid and 1,4-benzenedicarboxylic acid derivatives, namely (Ph₃Sn)₂(2,5-L¹)(C₂H₅OH)₂ (1) (2,5-H₂L¹ = 2,5-dibenzoylterephthalic acid), (Ph₃Sn)₂(2,5-L²)(C₂H₅OH)₂ (2) (2,5-H₂L² = 2,5-bis(4-methylbenzoyl)terephthalic acid), (Ph₃Sn)₂(2,5-L³)(C₂H₅OH)₂ (3) (2,5-H₂L³ = 2,5-bis(4-ethylbenzoyl)terephthalic acid), [(n-Bu₂Sn)₄(4,6-L¹)O₂(OH)(OC₂H₅)]₂·2(C₂H₅OH) (4) (4,6- H₂L¹ = 4,6-dibenzoylisophthalic acid), [(n-Bu₂Sn)₄(4,6-L¹)O₂(OH)(OC₄H₉)]₂·2(C₄H₉OH) (5) and [(n-Bu₂Sn)₄(4,6-L²)O₂(OH)(OC₂H₅)]₂·2(C₂H₅OH) (6) (4,6-H₂L² = 4,6-bis(4-methylbenzoyl)isophthalic acid), have been synthesized. All the organotin carboxylates have been characterized by elemental analysis, IR, ¹H and ¹³C NMR spectroscopy and X-ray crystallography diffraction analyses. The structural analysis reveals that complexes 1-3 show similar structures, containing binuclear triorganotin skeletons. The significant intermolecular O-H?O hydrogen bonds linked the complexes 1-3 to form a novel 2D network polymer with 38-member macrocycles. In complexes 4-6, two Sn₄O₄ ladders are connected by two 1,3-benzenedicarboxylic acid derivatives to yield ladder-like octanuclear architectures and form macrocycle with 24 atoms. In addition, the antitumor activities of complexes 1-6 have been studied.     

Synthesis and hypnotic activities of 4-thio analogues of N3-substituted uridines

Reaction of tri-O-acetyluridine (1) with benzyl bromide or 2-chloroacetophenone in the presence of K2CO3 gave the N3-substituted analogues 2a,c. Condensation of 1 with (+/-)-1-phenylethanol or 3,5-dimethylbenzyl alcohol using the Mitsunobu reaction also gave 2b,d in good yields. These compounds were allowed to react with Lawesson's reagent and were subsequently treated with ammonia to afford the 4-thiouracil derivatives 5a-d. Compounds 5a-c showed moderate hypnotic activity in mice. However, N3-(3,5-dimethyl)benzyl derivatives 3d, 5d were found to be almost inactive in this assay.     

Syntheses and properties of two chiral multidentate carboxylate copper coordination compounds

A chiral ligand, (R)-2-(4-(carboxymethoxy)phenoxy)propanoic acid, is employed as building block to construct two chiral coordination compounds, [Cu(L)(bipy)(H₂O)] (1) and [Cu₂(L)₂(phen)₄(H₂O)₁₃] (2), by the solvent-thermal method and the volatilization method, respectively. The compounds are characterized by single-crystal X-ray diffraction (XRD), IR spectra, XRD, TGA, and circular dichroism spectra. Compound 1 is comprised of right-handed helical chains and 2 shows a separated structure, both of which extend to 3-D supramolecular framework by hydrogen bonds and π?···?π interactions. CD indicates both compounds retain original stereo character with strong fluorescence at room temperature.     

Syntheses of highly fluorescent GFP-chromophore analogues

Eight B-containing compounds, i.e., 1a-h, were prepared as mimics of the green fluorescent protein (GFP) fluorophore. The underlying concept was that synthetic GFP chromophore analogues are not fluorescent primarily because of free rotation about an aryl-alkene bond (Figure 1b). This rotation is not possible in the beta-barrel of GFP; hence, the molecule is strongly fluorescent. In compounds 1a-h, radiationless decay via this mechanism is prevented by complexation of the BF2 entity. The target materials were prepared via two methods; most were obtained according to the novel route shown in Scheme 1b, but compound 1f was made via the procedure described in Scheme 2. Both syntheses involved formation of undesired compounds E-4a-h that formed simultaneously with the desired isomeric intermediates Z-4a-h. Both compounds form BF2 adducts, i.e., 1a-h and 5a-h, respectively. Methods used for spectroscopic characterization and differentiation of compounds in the series 1 and 5 are discussed, and these are supported by single-crystal X-ray diffraction analyses for compounds 1c, 5c, 1f, and 5f. Electronic spectra of compounds 1a-h and 5a-h were studied in detail. Those in the 5 series were shown to be only weakly fluorescent, but the 1 series were strongly fluorescent compounds (comparable to the boraindacene, BODIPY, dyes). Compounds 1g and 1h are water soluble, and 1h has particularly significant potential as a probe, since it also has a carboxylic acid group for attachment to biomolecules.     

Syntheses of prodelphinidin B1, B2, and B4 and their antitumor activities against human PC-3 prostate cancer cell lines

Total synthesis of prodelphinidin B1, B2, and B4 has been accomplished. The key step is Lewis acid-mediated equimolar condensations between an epigallocatechin and/or a gallocatechin nucleophile and an epigallocatechin and/or a gallocatechin electrophile. The antitumor effects of synthetic prodelphinidin B1–B4 against human PC-3 prostate cancer cell lines have been investigated. These compounds showed significant antitumor effects. Their activity seemed to be little bit stronger than EGCG and prodelphinidin B3, known antitumor agent.     

N,N''''-二芳基己二酰二肼类化合物的合成及其结构表征

报道了N,N'-二芳基己二酰二肼类化合物的合成方法.以自制的己二酰二氯、取代苯肼为原料,以二氯甲烷为溶剂,用冰浴法合成了9种新型的N,N'-二芳基己二酰二肼类化合物.产品的结构经元素分析、IR、1HNMR等测试技术得到确证,产物的IR谱中,在3200～3400 cm-1出现2个N-H吸收峰,1H NMR谱中,在δ7.3～10.5之间有2个N-H吸收峰,产品的元素分析结果与理论值基本相符.收率81%～93%.     

Syntheses and luminescence of three lanthanide complexes constructed by flexible carboxylate ligand

Three new complexes, namely {[Ln(L)₃(2,2′-Bipy)] _n · H₂O} (Ln = Pr (I), Sm (II), and Nd (III)) (HL = 3-(2-hydroxyphenyl)propanoic acid), have been synthesized and structurally characterized. The structural determinations indicated (CIF files CCDC nos. 1472729 (I), 1472730 (II), 1472734 (III)) that I–III have similar dinuclear structures, which can be further linked into 2D sheet via the hydrogen bond interactions. Furthermore, the luminescent properties of I–III show the strong emissive power and feature.     

基于龙胆苦苷的二吲哚甲烷类拟单萜吲哚生物碱类似物合成及其抗肿瘤、逆转紫杉醇耐药活性研究

以环烯醚萜类化合物龙胆苦苷为合成模块,利用拟单萜吲哚生物碱的仿生合成途径和组合化学的研究思路,与色胺类衍生物(吲哚结构的活性单元片段)通过缩合反应,首次合成了23个二吲哚甲烷类拟单萜吲哚生物碱类似物。利用核磁共振波谱(NMR)和高分辨质谱(HRMS)等谱学手段对合成化合物的结构进行了表征,并初步评价了其抗肿瘤活性和逆转耐药活性。活性结果表明,化合物4i脱掉糖基保护基后的化合物5i对3种肿瘤细胞系(TE-1,CAL-62和FaDu)的抑制作用强于阳性对照盐酸阿霉素(Dox)。通过与紫杉醇的联合用药,发现部分化合物如4m、4n、4o、4r等能够有效降低人肺癌细胞紫杉醇耐药株A549/Taxol对紫杉醇的耐药性,具有良好的逆转耐药潜力。