具有叶绿素-a基本碳架的氯代二氢卟吩衍生物的合成

选择脱镁叶绿酸-a甲酯为起始原料, 经过化学结构修饰转换成其他叶绿素-a衍生物. 以过氧化氢/盐酸、N-氯代丁二酰亚胺(NCS)、氯化氢(或者浓盐酸)为氯化剂, 根据3-乙烯基和20-meso-位的不同化学反应活性, 通过亲电加成和亲电取代反应, 在二氢卟吩环上选择性地引进氯原子, 完成8种未见报道的具有叶绿素-a基本碳架的氯代二氢卟吩衍生物的合成. 所合成的新化合物均经UV, IR, 1H NMR及元素分析证明其结构.     

Alkyl and aryl substituted corroles. 1. Synthesis and characterization of free base and cobalt containing derivatives. x-ray structure of (Me(4)Ph(5)Cor)Co(py)(2)

The synthesis, spectroscopic properties, and electrochemistry of six different alkyl- and aryl-substituted Co(III) corroles are presented. The investigated compounds contain methyl, ethyl, phenyl, or substituted phenyl groups at the eight beta-positions of the corrole macrocycle and four derivatives also contain a phenyl group at the 10-meso position of the macrocycle. Each cobalt corrole undergoes four reversible oxidations in CH(2)Cl(2) containing 0.1 M tetra-n-butylammonium perchlorate and exists as a dimer in its singly and doubly oxidized forms. The difference in potential between the first two oxidations is associated with the degree of interaction between the two corrole units of the dimer and ranges from an upper value of 0.62 V, in the case of (Me(6)Et(2)Cor)Co, to a lower value of about 0.17 V, in the case of four compounds which have a phenyl group located at the 10-meso position of the macrocycle. These Co(III) corroles strongly coordinate two pyridine molecules or one carbon monoxide molecule in CH(2)Cl(2) media, and ligand binding constants were evaluated using spectroscopic and electrochemical methods. The structure of (Me(4)Ph(5)Cor)Co(py)(2) was also determined by X-ray diffraction. Crystal data: (Me(4)Ph(5)Cor)Co(py)(2).3CH(2)Cl(2).H(2)O, orthorhombic, a = 19.5690(4) A, b = 17.1070(6) A, c = 15.9160(6) A, V = 5328.2(5) A(3), space group Pna2(1), Z = 2, 35 460 observations, R(F) = 0.069.     

A new understanding on how heme metabolism occurs in heme oxygenase: water-assisted oxo mechanism

Heme metabolism by heme oxygenase (HO) is investigated with quantum mechanical/molecular mechanical (QM/MM) calculations. A mechanism assisted by water is proposed: (1) an iron-oxo species and a water molecule are generated by the heterolytic cleavage of the O-O bond of an iron-hydroperoxo species in a similar way to P450-mediated reactions, (2) a hydrogen atom abstraction by the iron-oxo species from the generated water molecule and the C-O bond formation between the water molecule and the α-meso carbon take place simultaneously. The water molecule is hydrogen-bonded to the oxo ligand and to the water cluster in the active site of HO. The water cluster can control the position of the generated water molecule to ensure the regioselective oxidation of heme at the α-meso position, at the same time, can facilitate the oxidation by stabilizing a positive charge on the water molecule in the transition state. A key difference between HO and P450 is observed in the structure of the active site; Thr252 in P450 blocks the access of the water molecule to the α-meso position, and can thus suppress the undesired heme oxidation for P450.     

Meso-meso linked corroles

The cascade reaction of sterically hindered dipyrromethanes and formaldehyde furnished meso(10)-meso(10') linked corroles--a new type of porphyrinoid--compounds with interesting photophysical properties.     

A new pentanuclear cyano-bridged complex [(Fe(II)(tetraazamacrocycle))3{mu-NC-FeIII(CN)5)2]: synthesis, spectroscopic and magnetic characterization

Hexacyanoferrate(III) reacts with [FeII(meso)(CH3CN)2](ClO4)2.2CH3CN (meso=5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) in acetonitrile/water mixture producing the title complex, where three [Fe(meso)]2+ units are connected by two [Fe(CN)6](3-) anions. Molecular modeling (MM+) shows a fairly linear molecule and M?ssbauer data are consistent with two terminal pentacoordinated low spin iron(II)-meso units linked to one hexacoordinated low spin iron(II)-meso through two hexacoordinated low spin iron(III) units. Spectroscopic characterization showed a typical mixed-valence charge transfer band and the degree of electron coupling was calculated to be H(AB)=678 cm(-1). Magnetic properties exhibited an antiferromagnetic exchange interaction between the iron(III) ions with a coupling constant J= -44 cm(-1).     

Preparation, electrochemical and spectral properties of N-methylated pyridylethynyl porphyrins

A new series of electron-deficient porphyrins were prepared by attaching one or two N-methylated 2-, 3- or 4-pyridylethynyl groups to the 10,20-meso positions of (5,15-biphenylporphinato)zinc(II). Electrochemical studies showed significant changes in the reduction potentials of these porphyrins, and N-methyl-2-pyridylethyne is the strongest electron-withdrawing substituent in the series. UV-visible spectra demonstrated largely red-shifted absorptions, and N-methyl-4-pyridylethyne has the greatest impact to the porphyrin absorptions. Electrochemical, UV-visible and EPR results concluded that porphyrins Zn2 and Zn6 reversibly undergo two one-electron porphyrin-ring reductions to their anion radicals then dianions. The first reductions of porphyrins Zn1, Zn3, Zn4 and Zn5 were irreversible one-electron transfer processes. The instability of these reduction products was suggested to result from the eletrophilic attacks at the substituents.     

Synthesis of cobalt A2B triaryl corroles bearing methoxy or hydroxyl groups and their activity in electrocatalytic hydrogen evolution

Four A₂B cobalt corrole complexes 1 – 4 appending two methoxy or hydroxyl groups on the 10-meso phenyl group had been synthesized. Four cobalt corroles showed high electrocatalytic activity for hydrogen evolution reaction (HER) in the organic phase and in the aqueous phase. The hydrogen evolution pathway was EECEC when using acetic acid as proton source. When trifluoroacetic acid was used as proton source, the hydrogen evolution route via EECEC or EECC depending on the concentration of trifluoroacetic acid. Cobalt corrole 4 showed the best HER performance with the k_obs of 122.68 s⁻¹ in organic phase and the TOF of 832.2 h⁻¹ in aqueous phase respectively. The results suggested the phenyl hydroxyl group at the cobalt corrole peripheral may act as the proton relay group in HER and the o-hydroxyl of phenyl was better than m- hydroxyl for proton relay.     

Synthesis of 2-phenylbenzofuran derivatives as testosterone 5 alpha-reductase inhibitor

A series of 2-phenylbenzofuran derivatives with a carbamoyl, alkylamino, or alkyloxy group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. Against rat enzyme, the carbamoyl derivatives had more potent inhibitory activities than the alkylamino or alkyloxy derivatives, and the 6-carbamoyl derivatives tended to be more potent than the 5-carbamoyl derivatives. Against human enzyme, the 6-substituted derivatives had more potent inhibitory activities than the 5-substituted derivatives. The 6-carbamoyl and 6-alkylamino derivatives tended to show stronger inhibitory activities against human type 1 enzyme than against type 2 enzyme, but they were not largely selective.     

Preparations of anthraquinone and naphthoquinone derivatives and their cytotoxic effects

Chrysophanol and 1,8-di-O-hexylchrysophanol derivatives having nucleic acid bases at position 5 were synthesized. Furthermore, derivatives of menadione substituted at position 11 (type A naphthoquinone derivatives) or methylmenadione substituted at position 7 (type B naphthoquinone derivatives) modified with nucleic acid bases, amines and thiocyano, selenocyano or thioacetyl groups were synthesized. The cytotoxic effects of these derivatives on HCT 116 cells, which poorly express P-glycoprotein (P-gp), and Hep G2 cells, which stably express P-gp, were evaluated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results were compared with those obtained using 5-fluorouracil (5-FU), which has been used clinically. Several of these derivatives exhibited markedly higher potent cytotoxic effects not only on HCT cancer cells but also Hep G2 cancer cells as compared with 5-FU.     

香豆素衍生物的TICT态和荧光介质效应

研究了八种７－氨基香豆素衍生物在纯溶剂和二元溶剂体系中的荧光特性。这些衍生物因氨基上Ｈ的取代程度的不同，在溶液中可以形成两种不同的氢键。一种是由溶剂分子提供Ｈ，在香豆素环的２位氧原子上形成的氢键；另一种是由溶质分子提供Ｈ，在香豆素衍生物的７－氨基酸上形成的氢键。     

Reaction of aldimine anions with vinamidinium chloride: three-component access to 3-alkylpyridines and 3-alkylpyridinium salts and access to 2-alkyl glutaconaldehyde derivatives

N-tert-Butylimino derivatives of aldehydes were deprotonated with LDA and reacted with vinamidinium chloride to give 2-alkylaminopentadienimine derivatives, which were isolated as their corresponding hydrochloride in 68-81% yield. Reaction of these derivatives with ammonium acetate or salts of primary amines, in n-butanol at 80 degrees C, afforded the corresponding 3-alkylpyridines or 3-alkylpyridinium salts in high yield. Alkaline hydrolysis of 2-alkylaminopentadieneimine derivatives allowed a practical accesss to potassium salts of 2-alkylglutaconaldehyde.     

羟基取代黄烷酮类化合物与NO的反应研究

羟基取代的黄烷酮与NO反应, 得到了羟基邻位或对位单硝基化产物. 随着反应时间的延长, 有羟基邻位和对位双硝基化以及羟基两个邻位双硝基化产物生成. 多羟基取代的黄烷酮可以生成多硝基化产物.     

Anticancer effect of A-ring or/and C-ring modified oleanolic acid derivatives on KB, MCF-7 and HeLa cell lines

New A-ring or/and C-ring modified methyl oleanolate derivatives were prepared. New simple method of synthesis of 3,12-diketone (3) from methyl oleanonate (2) was worked out. The obtained new compounds were tested for cytotoxic activity on KB, MCF-7 and HeLa cell lines. The derivatives had acetoxy, oxo or hydroxyimino function at the C-3 position and in some cases oxo, hydroxyimino or acyloxyimino group at the C-12 position. Almost all of the compounds showed strong cytotoxic activity, higher than unchanged oleanolic acid. The most active substances turned out to be the derivatives with acyloxyimino function, especially 4 and 8d.     

Modulating the reactivity of functionalized N,S-ketene acetal in MCR: selective synthesis of tetrahydropyridines and thiochromeno[2,3-b]pyridines via DABCO-catalyzed tandem annulation

An efficient and straightforward three-component synthetic protocol was developed to synthesize 1,2,3,4-tetrahydropyridine derivatives or thiochromeno[2,3-b]pyridine derivatives from β-aroylthioacetanilides or β-(2-haloaroyl)thioacetanilides, aldehydes, and aroyl acetonitriles via DABCO-catalyzed tandem [3 + 2 + 1] annulation and S(N)Ar reaction. This synthetic approach has the prominent features of high chemo-, stereo- (or enantio-), and unusual regioselectivity. In the domino processes, at least seven reactive sites were involved, and up to three covalent bonds and one functionalized pyridine ring were generated. This facile and efficient reaction is a quite general for the preparation of tetrahydropyridine derivatives or thiochromeno[2,3-b]pyridine derivatives.     

Oxidation-alcoholysis of organosilyl- and organogermyl-substituted ferrocenes in the presence of ferric ions

Eleven ferrocene derivatives bearing the MM (M = Si and/or Ge) substituent bonded directly to the ring have been found to undergo alcoholysis at the MM linkage in the presence of either ferric chloride or ferricenium tetrachloroferrate. It is suggested that the oxidation-reduction process between the ferrocene derivatives and ferric ions gives rise to the corresponding substituted ferricenium ions, which, in turn may readily undergo a nucleophilic attack by alcohol at the adjacent highly polarized MM bond. The reaction is thus very similar to the acid-catalyzed alcoholysis of these ferrocene derivatives.     

Flophemesyl derivatives of alcohols,phenols, amines and carboxylic acids: Derivatives for mass spectrometric ion monitoring and structure determination

The flophemesyl (or pentafluorophenyldimethylsilyl) derivatives of representative alcohols, phenols, carboxylic acids and amines show rather simple spectra with a few abundant ions at high mass, characteristic of the parent compound and a few ions at low mass characteristic of the flophemesyl group. These derivatives are useful in the structure determination of simple compounds, and for the determination by single or multiple ion monitoring of known compounds at low levels.     

20-O-acylcamptothecin derivatives: evidence for lactone stabilization

Convincing UV and NMR spectrophotometric evidence is presented which demonstrates that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are substantially more stable in the lactone form than the 20-OH parent. Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O-ether derivative of CPT underwent endocyclic ring opening at pH > or =8.5, while the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl PEG (or alkyl) carboxylate forms.     

Formation of indene derivatives from bis(cyclopentadienyl)titanacyclopentadienes with alkyl group migration via carbon-carbon bond cleavage

A novel type of migration of an alkyl group in the formation of indene derivatives from titanacyclopentadienes was found. When titanacyclopentadienes with four alkyl groups were heated at 50 degrees C in THF for 24 h under nitrogen, titanium dihydroindene complexes were formed. Oxidation of the dihydroindene complexes with oxygen or alkyl halides afforded indene derivatives with unusual migration of one alkyl group at the diene moiety to the five-membered ring of the indene derivatives.     

Synthesis and reactions of pyrido[3,2,1‐jk]carbazole‐4,6‐diones

Pyrido[3,2,1‐jk]carbazoles 1 , synthesized from carbazoles and alkyl‐ or arylmalonates, gave regioselective electrophilic substitution reactions at position 5 such as chlorination to 5‐chloro derivatives 2 , nitration to 5‐nitro compounds 3 , or hydroxylation to 5‐hydroxy derivatives 4 . 5‐Hydroxy compounds 4 gave on treatment with strong bases ring contraction to 5 , 6 or the ring opening product 7 . Exchange of the chloro group in 2 with azide or amines gave the corresponding azides 8 and the 5‐amino derivatives 9 and 10 . Alkylation of 1 with benzyl chloride or allyl bromide resulted in the formation of 5‐C‐alkylated products 11 together with 4‐alkyloxy derivatives 12 . J. Heterocyclic Chem., 48, 1039 (2011).     

Efficient Synthesis of Glycosylated Matijin‐Su Derivatives via Ultrasonic Irradiation

Matijin‐Su ( 1 ) is a phenylalanine dipeptide compound with anti‐hepatitis B virus (HBV) activity. Previous reports suggest that the synthesis of glycosylated Matijin‐Su derivatives needs at least 10 steps. To simplify the synthetic procedure, we have developed a shorter and more efficient method for the preparation via ultrasound irradiation. Two galactopyranosylated ( 2 ) and two glucopyranosylated ( 3 ) derivatives were synthesized in 6 or 7 steps. The overall yields for the total synthesis of galactopyranosylated derivatives were markedly increased to 39% ( 2a ) or 22% ( 2b ). And the yields for glucopyranosylated derivatives also reached 29% ( 3a ) or 16% ( 3b ).