Alkenyl Substituents Research Articles

Synthesis and QSAR Studies of New Conjugated Benzothiazole Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Syndiotactic polymerization of styrene catalyzed by alkenyl‐substituted cyclopentadienyltitanium trichlorides

AbstractCH2CHCH2CpTiCl3 (1), CH2CHCH2CH2CpTiCl3 (2) and CH3CH2CH3CpTiCl3 (3) have been synthesized and characterized. The influence of the alkenyl substituent groups on the catalyst activities in the syndiotactic polymerization of styrene was investigated. The catalyst activities decreased in the order CH2CHCH2CH2CpTiCl3 > CH3CH2CH2CH2CpTiCl3 > CH3CH2CH2CpTiCl3 > CH2CHCH2CpTiCl3 (CpC5H4). By using complex 1, the dependence of the activity on the concentration of methylaluminoxane, triisobutylaluminum and diisobutylaluminum hydride was investigated. Copyright © 2003 John Wiley & Sons, Ltd.

Synthesis of New MKC-442 Analogues Containing Alkenyl Chains or Reactive Functionalities at C-5

In an effort to obtain more insight into the interaction between HIV-1 reverse transcriptase (RT) and MKC-442 analogues, a new series of compounds was synthesized and evaluated for inhibition of HIV-1 replication. The modifications include bulky alkenyl substituents at the C-5 position of the uracil ring. Analogues with reactive centers (aldehyde and epoxide functionalities) at C-5 were also synthesized in an attempt to develop HIV drugs with improved activity against the Y181C mutants by forming a covalent bond to the mercapto group in cysteine in the hydrophobic pocket of the mutated RT. Difficulties in the syntheses show that the epoxides are chemically reactive, whereas the aldehydes are more stable. One of the alkenyl analogues showed activity against HIV-1 in the same range as MKC-442, whereas the reactive analogues were not active against HIV with the mutation Y181C in RT.

3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 14.1,2 Pyrolysis of oxazolidinylmethylene derivatives of Meldrum's acid – synthesis of N-alkenyl-3-hydroxypyrroles and related reactions

Flash vacuum pyrolysis (FVP) of the title compounds 14 and 17 at 600–625 °C (0.005 Torr) gives the N-alkenylpyrrolones 22 and 23 respectively. The mechanism is shown to involve hydrogen transfer and cyclisation of the methyleneketene intermediate (e.g.25) to a fused pyrrolone (e.g.28). This species fragments to create an azomethine ylide which provides the alkenyl substituent by a further hydrogen transfer. Similar reactions are shown by the thiazolidine derivatives 20 and 21, though in the latter case the initial bicycles 35 and 37 can be observed by NMR spectroscopy. When the normal sites for hydrogen transfer are blocked by substituents (as in compound 16) an alternative hydrogen transfer–cycloaddition sequence leads to the fused pyridin-4-one 43.

Synthesis and QSAR Studies of New Conjugated Benzothiazole Derivatives

A series of new push-pull 2-(ω-phenylalkenyl)benzothiazolium compounds with methyl groups in different positions of the conjugated alkenyl bridge were synthesized by alkylation and condensation. The antimicrobial testing has been carried out and the effect of the alkenyl substituent was investigated by the QSAR Free-Wilson method.

Synthesis and inotropic activity of 1-(O-aminoalkyloximes) of perhydroindene derivatives as simplified digitalis-like compounds acting on the Na(+),K(+)-ATPase.

A series of 5-substituted (3aS,7aR)-7a-methylperhydroinden-3a-ol derivatives bearing a 1(S)-(omega-aminoalkoxy)iminoalkyl or -alkenyl substituent was synthesized, starting from the Hajos-Parrish ketol 47, as simplified analogues of very potent 17beta-aminoalkyloximes with digitalis skeleton, previously reported. The target compounds were evaluated in vitro for displacement of the specific [3H]ouabain binding from the dog kidney Na(+),K(+)-ATPase receptor. Some of them revealed IC(50) values in the micromolar range. The most active compounds possess a cyclohexyl group in the 5(S) position and in position 1(S) the same aminoalkyloxime groups already reported for the digitoxigenin-like series in position 17beta. Although the ring conformation of these derivatives was comparable to that of uzarigenin, the binding affinities of the most active ones were 4/8-fold lower in comparison to that standard. Three compounds among those with the highest affinities were assayed in vitro for their inotropic activity on an electrically driven guinea pig left atrium and were found to be less potent than both digoxin, the most widely used inotropic agent, and the corresponding digitalis 17beta-aminoalkyloximes.

Calcium-Mediated Fulvene Couplings. 1. A Survey of 6,6-Dialkylfulvenes for the Formation of Bridged and Unbridged Calcocenes

The degree to which 6,6-dimethylfulvene, 6,6-diethylfulvene, and 6-cyclopentylidenefulvene form unbridged calcocenes in reductive coupling reactions with activated calcium were compared. The identification of alkenyl substituents along with alkyl substituents among the unbridged calcocenes confirms that hydrogen atom or proton transfer between dialkylfulvenes and their radical anions or dianions is responsible for the formation of unbridged calcocenes. The tendency to form unbridged calcocenes instead of ansa-calcocenes is higher for 6,6-diethylfulvene and 6-cyclopentylidenefulvene than for 6,6-dimethylfulvene. 1,1‘-Dicyclopentenylcalcocene, 1, which is formed in the reaction between cyclopentylidenefulvene and calcium, was purified and crystallographically characterized. Photolysis of 1 leads to [2+2] cyclization of the cyclopentenyl substituents to form 2, an ansa-calcocene with a tricyclo[3.3.0.0]decane-1,10-diyl bridge.

17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na(+),K(+)-ATPase receptor.

A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na(+),K(+)-ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some interactions are the classical ones already described in the literature; a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

Base-promoted isomerization of cis-4-formyl-2-azetidinones: chemoselective C4-epimerization vs rearrangement to cyclic enaminones.

Two simple, efficient, and complementary methods for the regiospecific C4-epimerization of cis-4-formyl-2-azetidinones 1-3 are described. The first method uses 40% aqueous dimethylamine as reagent in heterogeneous medium with benzene at room temperature, in the presence of benzyltributylammonium bromide (3-4 mol%) as the phase-transfer catalyst. This transformation tolerates alkyl, alkenyl, alkynyl, aryl, and alkoxy substituents at the C3 of the 2-azetidinone ring. However, limitations of this isomerization are as follows: (i) only N-(p-methoxyphenyl)-beta-lactams can be used, and (ii) transformation is less compatible with heteroatomic substituents bonded to the C3 position of the 2-azetidinone ring. A highly general solution to these problems relies on the use of sodium carbonate as the isomerization reagent in different solvents. We also describe a novel base-promoted rearrangement of the beta-lactam ring to cyclic enaminones 6 and 21, involving an E1cB-elimination reaction in cis-4-formyl-2-azetidinones.

In Vitro Biological Activities of a Series of 2.BETA.-Substituted Analogues of 1.ALPHA.,25-Dihydroxyvitamin D3.

Biological activities of a series of 2beta-substituted analogues of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] were evaluated in vitro in terms of their binding affinity with regard to calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). Additionally, reporter gene luciferase activities using either a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), in transfected rat osteoblast-like ROS17/2.8 cells, or a human VDR-GAL4 modified two-hybrid system in transfected human epitheloid carcinoma, cervix HeLa cells were examined. Binding affinity for VDR, transactivation potency on the target gene and VDR-mediated gene regulation of the hydroxyalkyl and hydroxyalkoxy 2beta-substituted analogues were almost comparable to those of 1alpha,25(OH)2D3, while the alkyl and alkenyl analogues were much less active than 1alpha,25(OH)2D3. This study investigated the biological evaluation of a series of 2beta-substituted analogues at the molecular level, with regard to the structural differences of alkyl, alkenyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, hydroxy and chloro substituents at the 2beta-position of 1alpha,25(OH)2D3.

Synthesis of Isoquinolines and Pyridines by the Palladium- and Copper-Catalyzed Coupling and Cyclization of Terminal Acetylenes

3-Substituted isoquinolines have been synthesized by the coupling of aryl- and alkenyl-substituted terminal acetylenes with the tert-butylimine of o-iodobenzaldehyde in the presence of a palladium catalyst. Alkyl-substituted acetylenes fail to undergo this annulation process. However, the intermediate iminoalkynes containing aryl, alkenyl, and alkyl substituents produced from these palladium-catalyzed reactions undergo copper-catalyzed cyclization in excellent yields and short reaction times. Isoquinolines and pyridines have thus been prepared in a one-pot synthesis via coupling of aryl-, alkenyl-, and alkyl-substituted terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes or 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the resulting iminoalkynes. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing this palladium-catalyzed coupling/cyclization...

Potassium Organotrifluoroborates: New Partners in Palladium-Catalysed Cross-Coupling Reactions

The preparation of various potassium organotrifluoroborates bearing either aryl, alkenyl, or alkynyl substituents is described. These stable salts are shown to be very efficient partners in palladium-catalysed cross-coupling reactions with arenediazonium salts, affording biaryl and styrene derivatives in high yields.

ChemInform Abstract: Intramolecular Cyclization of (Z)‐N‐4‐Alkenylnitrones and the Effects of Alkenyl Substituents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Intramolecular cyclisation of ( Z)- N-4-alkenylnitrones and the effects of alkenyl substituents

The intramolecular 1,3-dipolar cycloaddition reactions of ( Z)- N-4-alkenylnitrones carrying various alkenyl substituents were investigated, and the regiochemistry of the resulting isoxazolidines was determined. Silyl- and bromo-substituents were found to effect significant regiocontrol on the intramolecular nitrone dipolar cycloaddition reaction.

Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters.

In our efforts to identify molecules that might act as cocaine antagonists or cocaine partial agonists, we have been involved in efforts to further elucidate the nature of cocaine's binding to the dopamine transporter (DAT) through strategic modifications of its structure. In the case of the substituent located at the 2-position of the tropane ring, studies have revealed the ability of the transporter to accommodate groups of diverse structure, including ester, ketone, alkyl, alkenyl, heterocyclic, and aryl substituents, without loss of DAT binding affinity. In the present study, we report our results pertaining to the ability of the DAT to accommodate the WIN-type structures possessing alkyl or aryl groups at the 2-position and which adopt either a chair or a boat conformation of the tropane ring. Moreover, we discuss the influence of the stereochemistry of these compounds in their selectivity for the DAT versus the serotonin transporter (5HTT). Additionally, we point out the importance of using Ki values rather than IC50 values when making such comparisons of transporter selectivity. One of the most interesting compounds identified in the present work is a 2, 3-diaryltropane 22 in a boat conformation that is highly selective (69-fold) for the DAT over the 5HTT. The ability to prepare this compound as well as related structures by our oxidopyridinium betaine-based dipolar cycloaddition strategy further underscores the versatility of this particular chemical approach to the preparation of diverse tropane analogues. The use of the optically pure olefin p-tolyl vinyl sulfoxide as the dipolarophile in this reaction allows access to these novel tropanes in nonracemic form.

Nickel-catalyzed regio- and stereoselective homo 1,4-dialkenylation of conjugated dienes

2,3-Dimethyl-1,3-butadiene and cyclic dienes react with β-iodoenones (RI: 3-Iodo-2-cyclohexen-1-one, 5,5-dimethyl-3-iodo-2-cyclohexen-1-one and 3-iodo-2-cyclopenten-1-one) in the presence of Zn and catalytic amount of NiBr 2 to afford the corresponding homo 1,4-addition products in good yields. For 2,3-dimethyl-1,3-butadiene, only the products RCH 2C(CH 3)=C(CH 3)CH 2R with Z geometry were observed. For cyclic dienes, the products observed are R CHCH=CHCHR(CH 2) nC H 2 in which the two alkenyl substituents R are cis to each other.

Selbstimmobilisierende Metallocenkatalysatoren

A novel method for the preparation of heterogeneous metallocene catalysts is described that can be applied for the polymerization of olefins starting with homogeneous metallocene complexes. For this purpose zirconocene dichloride complexes have been prepared containing alkenyl or alkynyl substituents. These complexes can be activated with methyl alumoxane (MAO) and then are incorporated as comonomers into the formed polyolefin chain. The homogeneous metallocene catalysts become self-immobilizing under the reaction conditions and the further formation of the polyolefin is then catalyzed heterogeneously.

Shortcut Syntheses of Naturally Occurring 5-Alkylresorcinols with DNA-Cleaving Properties.

Resorcinols such as 1-5 bearing long alkyl- or alkenyl substituents at the C-5 position, including bola-formed bis-resorcinol derivatives, have recently been isolated from natural sources and were shown to exhibit exceptional DNA-cleaving properties under oxidative conditions. Previous synthetic approaches to such compounds seem inappropriately lengthy with regard to their structural simplicity. Disclosed is a very flexible synthesis which assembles these targets from triflate 7 and well accessible alkenes, dienes, enynes, or dienynes, respectively, by means of a boron-mediated reaction manifold. As a typical example, hexadeca-1,15-dien-8-yne 11 is hydroborated with 9-H-9-BBN at all possible sites, the alkenyl borane entity of the resulting tris-borane 12 is selectively cleaved off to afford the desired (Z)-alkene group in a stereoselective manner, the remaining two terminal alkylboranes are treated with NaOMe, and the bis-borate complex 13 thus formed is finally used as the nucleophile for a palladium-catalyzed Suzuki cross-coupling reaction with triflate 7. This sequence is carried out in one pot and provides product 14 in 62% overall yield. Demethylation of 14 (and analogues) can be conveniently achieved by means of 9-iodo-9-BBN to afford the natural product 5. The efficiency and flexibility of this unprecedented approach which combines different features of classical and modern boron chemistry is further demonstrated by the synthesis of anacardic and ginkgolic acid derivatives.

New Anticandidous 2-Alkylthio-6-aminobenzothiazoles

The synthesis and antimicrobial activity of six new 2-alkenyl-6-aminobenzothiazoles are reported. The new compounds were prepared by alkenylation of the potassium salt of 6-amino-2-mercaptobenzothiazole with alkenyl bromides. The structure of the compounds was verified by 1H NMR spectra. The compounds have shown antibacterial activity against Staphylococcus aureus and anticandidous activity against Candida albicans. The optimum structure of the studied compounds has been calculated by quantum chemistry AM1 method. The theoretical values of lipophilicity were calculated for all alkenyl substituents.

Monomer−Trimer Isomerism in 3-Substituted Pentane-2,4-dione Derivatives of Nickel(II)

Bis(η3-allyl)nickel reacts with pentane-2,4-dione derivatives having alkenyl substituents in the 3-position to give Ni(3-R-pentane-2,4-dionato)2 compounds which have been shown by X-ray diffraction and NMR spectroscopy to be monomeric [R = 5-hexenyl, C22H34NiO4, a = 13.718(3) Å, b = 4.962(1) Å, c = 16.643(3) Å, β = 92.46(3)°, space group P21/n, Z = 2; R = 7-octenyl, C26H42NiO4, a = 4.8449(5) Å, b = 8.3202(8) Å, c = 16.792(1) Å, α = 89.480(4)°, β = 88.240(4)°, γ = 77.30(1)°; R = 9-decenyl, C30H50NiO4, a = 4.8067(2) Å, b = 8.2809(3) Å, c = 19.4014(7) Å, α = 90.974(4)°, β = 91.907(4)°, γ = 102.495(4)°, space group P1̄, Z = 1; R = methyl, C12H18NiO4, a = 4.9447(4) Å, b = 8.0649(7) Å, c = 9.0633(6) Å, α = 109.377(6)°, β = 93.706(7)°, γ = 106.283(7)°, space group P1̄, Z = 1; R = phenylethano, C26H30NiO4, a = 12.792(1) Å, b = 6.503(1) Å, c = 14.933(1) Å, β = 109.025(7)°, space group P21/n, Z = 2] in the crystal and in solution at room temperature. No inter- or intramolecular interaction of the alkenyl substituent with the 16e metal atom is observed. The corresponding Ni compounds containing the 3-phenyl-substituted dione have been shown to adopt both monomeric [C22H22NiO4, a = 10.2261(5) Å, b = 6.6439(3) Å, c = 13.7862(7) Å, β = 93.677(6)°, space group P21/n, Z = 2] and trimeric [(C22H22NiO4)3, a = 10.5917(7) Å, b = 12.3092(8) Å, c = 12.5926(5) Å, α = 103.937(4)°, β = 96.388(3)°, γ = 96.227(5)°, space group P1̄, Z = 1] forms in the crystal while the compound formed by tert-butyl acetoacetate [(C16H26NiO6)3, a = 9.713(1) Å, b = 17.550(1) Å, c = 17.391(1) Å, β = 100.272(5)°, space group P21/n, Z = 2] is a trimer in which the central Ni atom interacts solely with bridging acetyl groups. The crystal structure of 3-phenyl-2,4-pentanedione [C11H12O2, a = 19.2961(6) Å, b = 6.8561(2) Å, c = 7.5935(2) Å, space group Pnma, Z = 4] has also been determined.