摘要:

AbstractThe synthesis and structural characterization of the macrobicyclic ligand1containing a reducible hexakis‐(phenylthio)benzene electron‐acceptor site is described. It is based on the condensation of the tetraoxa‐diazamacrocycle3with a suitably functionalized derivative4of hexakis(phenylthio)benzene. Complexation of a potassium cation by1gives the corresponding cryptate2, with a stability constant ofca.4000M−1as determined by1H‐NMR titration in CD3CN. The reduction potential of the hexakis(phenylthio)benzene electron‐acceptor site in2is shifted by 170 mV towards more positive values with respect to that in1by complexation o

ISSN:0018-019X    

DOI:10.1002/hlca.19970800802

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractEnantiomeric oligoribonucleotides (=ent‐RNA) up to a sequence length of thirty‐five and consisting of the (L‐configurated) nucleosidesent‐adenosine,ent‐guanosine,ent‐cytidine,ent‐uridine, and 1‐(β‐L‐ribofuranosyl)thymine were prepared by automated synthesis from appropriate building blocks, carrying a known photo‐labile 2′‐O‐protecting group. A simple large‐scale synthesis of the new, prefunctionalizedL‐ribose derivative5fromD‐glucose (Scheme 1) and its straightforward conversion into the five phosphoramidites28–32and five solid supports38–42, respectively, were elaborated (Scheme 4). Within this project, a novel, superior strategy for the synthesis of the 2′‐O‐{[(2‐nitrobenzyl)oxy]methyl}‐substituted key intermediates18–22by regioselective alkylation of their 5′‐O‐dimethoxytritylated precursors13–17was developed. Furthermore, an improved set‐up for the final light‐induced cleavage of the 2′‐O‐protecting groups from the oligonucleotide sequences was designed (Scheme 5andFig. 1). The correct composition of allent‐oligoribonucleotides prepared was established by their MALDI‐TOF mass spectra. The1H‐NMR‐spectroscopic data of a dodecamericent‐RNA sequence was in excellent agreement with the published data of its natural counterpart, synthesized by conventional methods. The known specific cleavage of a tetradecamer sequence by a 35mer ribozyme structure could be reprod

ISSN:0018-019X    

DOI:10.1002/hlca.19970800803

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractThree bis‐macrocyclic ligands consisting of two N3‐, N2S‐, or NS2‐cyclononane rings, i.e., of two octahydro‐1H‐1,4,7‐triazonine, octahydro‐1,4,7‐thiadiazonine, or hexahydro‐5H‐1,4‐7‐dithiazonine rings, connected by a 1H‐pyrazolediyl unit were prepared. They form dinuclear CuIIand NiIIcomplexes which are able to bind one additional exogenous bridging molecule such as Cl−, Br−, N −3−, SO 42−, and 1H‐pyrazol‐1‐ide. The structures determined by X‐ray diffraction show that each Cu2+is coordinated by the three donor atoms of the macrocyclic ring, by a pyrazolidodiyl N‐atom, by an atom of the exogenous bridging ligand, and sometimes by a solvent molecule. In the majority of the Cu2+cases, the metal ion exhibits square‐pyramidal or trigonal‐bipyramidal coordination geometry, except in the sulfato‐bridged complex, in which one Cu2+is hexacoordinated with the participation of a water molecule. The X‐ray structure of the azide‐bridged dinuclear Ni2+complex was also solved and shows that both Ni2+centres have octahedral coordination geometries. In all complexes, the 1H‐pyrazolediyl group connecting the macrocycles is deprotonated and bridges the two metal centres, which, depending on the exogenous ligand, have distances between 3.6 and 4.5 Å. In the dinuclear Cu2+complexes, antiferromagnetic coupling is present. The azido‐bridged complex shows a very strong interaction with −2J≥ 1040 cm−1; in contrast, theH‐pyrazol‐1‐ide and chloride bridged species have −2Jvalues of 300 and 272cm−1, respectively. Cyclic voltammetry of the Cu2+complexes in MeCN reveals a strong dependence of the potentials CuII/Cu‐II→ CuII/CuI→ CuI/CuIon the nature of the donor atoms of the macrocycle as well as on the type of bridging molecule. The more S‐donors are present in the mac

ISSN:0018-019X    

DOI:10.1002/hlca.19970800804

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractX‐Ray crystal structure of 4‐(methylthio)‐4‐nitro‐1‐(pyrrolidin‐1‐yl)buta‐1,3‐diene (2b)The C‐atoms of the butadiene chain have been numbered as shown in1and2. These numbers have been retained throughout the discussion for the sake of clarity and consistency.indicates the presence of a CH…︁S hydrogen bond. This might also explain the observed downfield shift

ISSN:0018-019X    

DOI:10.1002/hlca.19970800805

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractIn a search for inhibitors of platelet aggregation, a number of α‐methylidene‐γ‐butyrolactones5and6bearing flavone or xanthone moieties, respectively, were synthesized and evaluated for their antiplatelet activity against thrombin(Thr)‐, arachidonic‐acid(AA)‐, collagen(Col)−, and platelet‐activating‐factor(PAF)‐induced aggregation in washed rabbit platelets. These compounds were synthesized from 7‐hydroxyflavone (1) or 3‐hydroxyxanthone (2)via O‐alkylation (→3and4, resp.) andReformatsky‐type condensation (Scheme). Most of the flavone‐containing α‐methylidene‐γ‐butyrolactones5a–dshowed potent antiplatelet effects on AA‐ and Col‐induced aggregation, while xanthone derivatives6c–ewere found to have the same pharmacological profile than aspirin in which only AA‐induced aggregation was inhibited (Table 1). However,6c–ewere approximately three to ten times more potent than aspirin (Table 2). For the vasorelaxing effects,5awas the only compound which exhibited significant inhibitory activity on the high‐K+medium, Ca2+‐induced vasoconstriction (Table3). Both5aand6a, with an aliphatic Me substituent at C(γ) of the lactone, were active against norepinephrine‐induced phasic and tonic constrictions while t

ISSN:0018-019X    

DOI:10.1002/hlca.19970800806

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractAn approach to a new class of cyclic hydroxamic acids is described leading to a formal combination of a benzoxazine subunit related to some natural aglucones occurring in plants with the steroidal skeleton from two members of the estra‐1,3,5(10)‐triene series. The annelation procedure for a 4‐hydroxy‐1,4‐oxazine moiety to the aromatic A‐ring in estrone (1) and 1‐hydroxy‐4‐methylestra‐1,3,5(10)‐trien‐17‐one (7), used as steroidal precursors, proceeds in four or three steps, respectively (Schemes 1and2, resp.). First, a 2‐nitro group is introduced regioselectively by a novel nitrosation‐oxidation procedure or by conventional nitration (→ nitrophenols2and8). Reaction of the phenolic unit of2and8with methyl bromoacetate or ethyl chlorooxoacetate gives rise to the nitro esters3,4,9, and10, which are subjected to reductive cyclization either by means of Zn dust in ammonium chloride solution (for the acetates) or of H2/Pt(S)/C (for the sensitive oxalates). Hence, the novel cyclic hydroxamic acids5,6, 11, and12of the estra‐1,3

ISSN:0018-019X    

DOI:10.1002/hlca.19970800807

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractGinkgolide B (1b) has been glucosylated in THF with the glucosylidene‐derived diazirine2under thermal or photochemical conditions. Depending on the amount of2, we obtained either monoglucosides (5–8), diglucosides (13–17), or triglucosides (21–23). In keeping with earlier results, the use of THF as solvent led mostly to β‐D‐glucosides. The modest regioselectivity in the formation of the monoglucosides, glucosylated either at OC(1) or OC(10), is rationalized on the basis of the relative kinetic acidity of the intra‐ and intermolecularly H‐bonded OH groups of1b. The tertiary HOC(3) of the monoglucosides was more readily glucosylated than the secondary HOC(1) or HOC(10) (H‐bonded). Glucosidation with 3.5 equiv. of2led to triglucosides, with the tri‐β‐D‐glucoside 21 (42%) as the major product. Catalytic hydrogenation afforded the free glucosides9–12,18–20, and24. The di‐ and triglucosides are readily soluble in H2O. Glucosidation with 2 of the ginkgolide‐A‐derived tertiary alcohol 25 yielded 93% of the β‐D‐anomeric glucoside26. Similarly, glycosidation of25with the lactosylidene‐derived diazirine34proceeded with a very high stereoselectivity, yielding 92% of the β‐D‐lacto

ISSN:0018-019X    

DOI:10.1002/hlca.19970800808

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractCyclophanes3and4were prepared as initiator cores for the construction of dendrophanes (dendritic cydophanes)1and2, respectively, which mimic recognition sites buried in globular proteins. The tetra‐oxy[6.1.6.1]paracyclophane3was prepared by a short three‐step route (Scheme 1) and possesses a cavity binding site shaped by two diphenylmethane units suitable for the inclusion of flat aromatic substrates such as benzene and naphthalene derivatives as was shown by1H‐NMR binding titrations in basic D2O phosphate buffer (Table 1). The larger cyclophane4, shaped by two wider naphthyl(phenyl)methane spacers, was prepared in a longer, ten‐step synthesis (Scheme 2) which included as a key intermediate the tetrabromocyclophane5.1H‐NMR Binding studies in basic borate buffer in D2O/CD3OD demonstrated that4is an efficient steroid receptor. In a series of steroids (Table 1), complexation strength decreased with increasing substrate polarity and increasing number of polar substituents; in addition, electrostatic repulsion between carboxylate residues of host and guest also affected the binding affinity strongly. The conformationally flexible tetrabromocyclophane5displayed a pronounced tendency to form solid‐state inclusion compounds of defined stoichiometry, which were analyzed by X‐ray crystallography (Fig. 2). 1,2‐Dichloroethane formed a cavity inclusion complex5awith 1:1 stoichiometry, while in the 1:3 inclusion compound5bwith benzene, one guest is fully buried in the macrocyclic cavity and two others are positioned in channels between the Cyclophanes in the crystal lattice. In the 1:2 inclusion compound5c, two toluene molecules penetrate with their aromatic rings the macrocyclic cavity from opposite sides in an antiparallel fashion. On the other hand,p‐xylene (= 1,4‐dimethylbenzene) in the 1:1 compound5dis sandwiched between the cyclophane molecules with its two Me groups penetrating the cavities of the two macrocycles. In the 1:2 inclusion compound 5e with tetralin (= 1,2,3,4‐tetrahydronaphthalene), both host and guest are statically disordered. The shape of the macrocycle in5a–edepends strongly on the nature of the guest (Fig. 4). Characteristic for these compounds is the pronounced tendency of 5 to undergo regular stacking and to form channels for guest inclusion; these channels can infinitely extend across the macrocyclic cavities (Fig. 6) or in the crystal lattice between neighboring cyclophane stacks (Fig. 5). Also, the crystal lattice of5cdisplays a remarkable zig‐zag pattern of short Br…︁O contacts between nei

ISSN:0018-019X    

DOI:10.1002/hlca.19970800809

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractWater‐soluble dendritic cyclophanes (dendrophanes) of first (1,4), second (25), and third generation (36) with poly(ether amide) branching and 12, 36, and 108 terminal carboxylate groups, respectively, were prepared by divergent synthesis, and their molecular recognition properties in aqueous solutions were investigated. Dendrophanes1–3incorporate as the initiator core a tetraoxa[6.1.6.1]paracyclophane7with a suitably sized cavity for inclusion complexation of benzene or naphthalene derivatives. The initiator core in4–6is the [6.1.6.1]cyclo‐phane8shaped by two naphthyl(phenyl) methane units with a cavity suitable for steroid incorporation. The syntheses of1–6involved sequential peptide coupling to monomer9, followed by ester hydrolysis (Schemes 1and4), Purification by gel‐permeation chromatography (GPC;Fig. 3) and full spectral characterization were accomplished at the stage of the intermediate poly(methyl carboxylates)10–12and23–25, respectively. The third‐generation 108‐ester25was also independently prepared by a semi‐convergent synthetic strategy, starting from4(Scheme 5). All dendrophanes with terminal ester groups were obtained in pure form according to the13C‐NMR spectral criterion (Figs, 1and5). The MALDI‐TOF mass spectra of the third‐generation derivative25(mol. wt. 19328 D) displayed the molecular ion as base peak, accompanied by a series of ions [M–n(1041 ± 7)]+, tentatively assigned as characteristic fragment ions of the poly(ether amide) cascade. A similar fragmentation pattern was also observed in the spectra of other higher‐generation poly(ether amide) dendrimers. Attempts to prepare monodisperse fourth‐generation dendrophanes by divergent synthesis failed.1H‐NMR and fluorescence binding titrations in basic aqueous buffer solutions showed that dendrophanes1–3complexed benzene and naphthalene derivatives, whereas4–6bound the steroid testosterone. Complexation occurred exclusively at the cavity‐binding site of the central cyclophane core rather than in fluctuating voids in the dendritic branches, and the association strength was similar to that of the complexes formed by the initiator cores7and8, respectively (Tables 1and3). Fluorescence titrations with 6‐(p‐toluidino)naphthalene‐2‐sulfonate as fluorescent probe in aqueous buffer showed that the micropolarity at the cyclophane core in dendrophanes1‐3becomes increasingly reduced with increasing size and density of the dendritic superstructure; the polarity at the core of the third‐generation compound 3 is similar to that of EtOH (Table 2). Host‐guest exchange kinetics were remarkably fast and, except for receptor3, the stabilities of all dendrophane complexes could be evaluated by1H‐NMR titrations. The rapid complexation‐decomplexation kinetics are explained by the specific attachment of the dendritic wedges to large, nanometer‐sized cyclophane initiator cores, which g

ISSN:0018-019X    

DOI:10.1002/hlca.19970800810

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractMethyl 2‐acetyl‐3‐{[2‐(dimethylamino)‐1‐(methoxycarbonyl)ethenyl]amino}prop‐2‐enoate (4) and phenyl‐methyl 2‐acetyl‐3‐{[2‐(dimethylamino)‐1(methoxycarbonyl)ethenyl]amino}prop‐2‐enoate (5) were prepared in three steps from the corresponding acetoacetic esters, and used as reagents for the preparation ofN3‐protected 3‐amino‐4H‐pyrido[1,2‐a]pyrimidin‐4‐ones10–12, 5H‐thiazolo[3,2‐a]pyrimidin‐5‐one13, 4H‐pyrido[1,2‐a]‐pyridin‐4‐one19and 2H‐1‐benzopyran‐2‐ones20–23. Free 3‐amino‐4H‐pyrido[1,2‐a]pyrimidin‐4‐ones24–26were prepared from10–12by removal of the 2‐(methoxycarbonyl)‐3‐oxob

ISSN:0018-019X    

DOI:10.1002/hlca.19970800811

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY