Alkenyl Side Chain Research Articles

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. I. Taxonomy, fermentation, isolation and structural elucidation.

A new series of antifungal antibiotics, Ro 09-1470 and its 6 congeners were isolated from the fermentation broth of Penicillium sp. NR6564. Their structures were determined as tetrahydropyran derivatives with an alkenyl side chain on the basis of their spectroscopic and physico-chemical properties. Among these compounds, Ro 09-1470 and Ro 09-1545 possessing a glycyl N-substituted glycyl ester residue had high antifungal activity. Ro 09-1469, one of the congeners, was found in the fermentation broth of several strains of Aspergillus sclerotiorum Huber.

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. II. Mode of action.

From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi.

Synthèse d'isoxazoles substitués en α de l'oxygène et d'isoxazoles substitués en α de l'azote et de l'oxygène par des chaînes alkyle ou alcényle

Two series of isoxazoles substituted by long alkyl or alkenyl chains in the α position with respect to the oxygen atom or in the α position with respect to the two heteroatoms have been synthesized. Starting from 3,5-dimethylisoxazole, the regioselective metalation/alkylation on the α-O methyl group was a very convenient route to a large variety of "α-O substituted isoxazoles". When applied to α-O methylated isoxazoles bearing an α-N alkenyl chain the same method provides an original unequivocal approach to 3,5-dialkenyl isoxazoles. An alternative route to these compounds, despite the formation of di-isoxazoline as by-product and an additional step corresponding to the oxidation of the intermediate isoxazoline, is the 1,3-dipolar cycloaddition, by using terminal dienes as dipolarophiles with alkenyl dipoles. Nevertheless, the cycloaddition between monoalkylated alcynes and alkylated dipoles remains the most straightforward synthesis of 3,5-dialkyl isoxazoles. Key words: isoxazoles, alkenyl side chains, metalation–alkylation, regioselectivity.

Synthèse d'isoxazoles substitués en α de l'azote par une chaine alkyle ou alcényle

Several syntheses of special isoxazoles bearing a long alkyl or alkenyl side chain in the α position of the nitrogen are presented. A very convenient route in the case of an alkyl side chain is the classical 1,3-dipolar cycloaddition of a nitrile-oxide to a vinyl acetate. Although it is a rather long approach, the reaction of hydroxylamine with enone-epoxides represents a new and unequivocal method compatible with alkenyl side chains. The isomerisation of the easily synthesized isoxazoles bearing such substitutents α to the oxygen, by the reaction of their isoxazolium salts with hydroxylamine, is a fast and general method. Another very convenient access to "α-N substituted" isoxazoles is the coupling of magnesium compounds with 3-bromomethyl 5-methyl isoxazole. Keywords: isoxazoles, substitution in the α position of nitrogen.

Synergisms, structure-material relations and display performance of novel fluorinated alkenyl liquid crystals

Abstract Several new classes of low polarity, low viscosity and optically weakly anisotropic two and three ring fluorinated liquid crystals with alkenyl side chains are presented. Synergisms which lead to a number of favourable material properties are shown to result from systematic changes of (a) para and lateral fluorination of the benzene ring in the rigid cores, (b) variations of double bond positions in the alkenyl side chains and (c) from replacing cyclohexane core rings by dioxane rings. A broad range of dielectric anisotropies −0.3 < Δ∊ < 13, broad nematic meso-phases, low rotational, λ and bulk viscosities, n, (22°C) < 10cP as well as visco elastic ratios as low as λ/k (22°C) = 3.8 × 10–12m-12s-1 follow; were K = K11 + (K33 - 2K22)/4. As a consequence a wide range of optical threshold voltages V10 and short response times result in field-effect liquid crystal displays. The low ratios κ/Δ∊ of the heterocyclic representatives among the new compounds lead in twisted nematic displays to threshold vol...

Vinyl azides in heterocyclic synthesis. Part 10. Synthesis of the isoindolobenzazepine alkaloid lennoxamine

A total synthesis of the isoindolobenzazepine alkaloid lennoxamine (1), by a route involving vinyl azide chemistry, is described. Model studies on the azidocinnamates (12) and (13) revealed a striking difference between the (E)-and (Z)-isomers; whereas the (Z)-isomer (12) and gave largely the 1-benzylisoquinoline (15) on decomposition, the (E)-isomer (13) gave the 2-aryl-3-benzazepine (14) as the major product. Consequently, in the lennoxamine synthesis, the azidocinnamate (26) bearing the (E)-alkenyl side chain, prepared from 6-bromopiperonal via the (E)-stilbene aldehyde (25)(Scheme 4), was decomposed to give the key 2-aryl-3-benzazepine (27). Reduction of the double bonds in (27) was accompanied by cyclisation to the tetrahydroisoindolo[1,2-b][3]benzazepine (30), which was converted into lennoxamine (1) by reduction of the ester group to an aldehyde, and decarbonylation.

Mass spectrometric fragmentation patterns of isomeric 5-methyl-3-alkyl-2-alkenylpyrazines

The detailed mass spectral fragmentation pathways of a series of both naturally occurring and synthetic 5-methyl-3-alkyl-2-aIkenylpyrazines have been elucidated with the aid of deuterium labels placed specifically in the alkenyl side-chain. The influence on the fragmentation pattern of the stereochemistry of the alkenyl group as well as the relative placement of the groups on the pyrazine nucleus have also been evaluated. This provides information of some diagnostic value in the assignment of structures by mass spectrometry to new compounds within this class.

Invited Lecture. Material properties, structural relations with molecular ensembles and electro-optical performance of new bicyclohexane liquid crystals in field-effect liquid crystal displays

Abstract Several new classes of polar and non-polar bicyclohexane liquid crystals comprising alkenyl side chains are presented. The compounds exhibit low optical anisotropies, Δn, 12 × 10−12 N, to low viscoelastic ratios γ1/k and to short response times in field-effect liquid crystal displays (LCDs). Strong odd-even effects occur in the bend/splay elastic ratio k 3/k 1 upon shifting the alkenyl double bond from even into odd side chain positions. As a result the ratio k 3/k 1 can be tuned over the wide range 0·9 ≲ k 3/k 1 ≲ 3·0. Correlations between the electro-optical properties of twisted nematic, supertwisted nematic, optical mode interference LCDs and material parameters demonstrate the high degree of multiplexability of the new compounds. Roche interactive molecular modelling is applied to determine the possible equilibrium configuration not only of singl...

ChemInform Abstract: Chain Ordering in Cyanobiphenyls and Cyanophenylcyclohexanes

Two-dimensional carbon-13 n.m.r. has been used to study the chain ordering of two cyanobiphenyls (6CB and 7CB) as a function of temperature. The C—H bond order parameters of 6CB and 7CB were calculated with the method of the potential of mean torque, using parameters obtained from 5CB and 8CB. The results agree very well with the experimental data. The orientational ordering of three 4′-cyanophenylcyclohexanes, two of which contain alkenyl side chains, has also been investigated. Trends of calculated C—H order parameters agree with those of experimental values, but the numerical agreements are less satisfactory than those for the cyanobiphenyls. The discrepancies are attributed to simplifications in the model. The two major contributing factors are the assumption of a cylindrical core and a simplified potential form for the rotation about the C—C bond joining the cyclohexane ring and the aliphatic chain. Calculated C—C bond order parameters of the three cyanophenylcyclohexanes and four cyanobipnenyls are also presented, and their trends are discussed.

Studies on the effect of stigmatellin derivatives on cytochrome b and the Rieske iron-sulfur cluster of cytochrome c reductase from bovine heart mitochondria.

Stigmatellin and its derivatives represent a third class of Qo site inhibitors besides the hydroxyquinone derivatives and the E-beta-methoxyacrylate (MOA) inhibitors [von Jagow and Link (1986) Methods Enzymol. 126, 253-271]. The stigmatellins consist of a chromone ring system connected to an substituted alkenyl side chain. Alterations in the side chain, i.e. saturation of the C = C double bonds, shift of a methoxy group or loss of the methyl groups, specifically affect the binding characteristics. Besides changing the red shift spectrum of reduced cytochrome b566 and the EPR spectrum of the Rieske iron-sulfur cluster, the side chain alterations diminish the binding affinity and the extent of the midpoint potential shift of the iron-sulfur protein. Thus, the side chain of the molecule makes an essential contribution to the binding energy and is not necessary solely for partitioning the molecule into the hydrophobic phase, as assumed so far.

Chain ordering in cyanobiphenyls and cyanophenylcyclohexanes

Two-dimensional carbon-13 n.m.r. has been used to study the chain ordering of two cyanobiphenyls (6CB and 7CB) as a function of temperature. The C—H bond order parameters of 6CB and 7CB were calculated with the method of the potential of mean torque, using parameters obtained from 5CB and 8CB. The results agree very well with the experimental data. The orientational ordering of three 4′-cyanophenylcyclohexanes, two of which contain alkenyl side chains, has also been investigated. Trends of calculated C—H order parameters agree with those of experimental values, but the numerical agreements are less satisfactory than those for the cyanobiphenyls. The discrepancies are attributed to simplifications in the model. The two major contributing factors are the assumption of a cylindrical core and a simplified potential form for the rotation about the C—C bond joining the cyclohexane ring and the aliphatic chain. Calculated C—C bond order parameters of the three cyanophenylcyclohexanes and four cyanobipnenyls are also presented, and their trends are discussed.

ChemInform Abstract: Mercury(II)‐Promoted Cyclization of Some 2‐Alkenylphenols and Some Cyclic 2‐Alkenyl‐1,3‐diketones, 3‐Keto Esters, and 3‐Keto Amides: Synthesis of 2,3‐Dihydrofuran, 3,4‐Dihydro‐2H‐pyran, and 2,3,4,5‐Tetrahydrooxepin Rings Fused on Carbocyclic or on Oxygen and Nitrogen Heterocyclic Systems.

AbstractMercuration of the corresponding hetero or carbocyclic compounds bearing a hydroxyl and a proper alkenyl side chain in o‐position leads to the chloromercurymethyl substituted oligocyclic systems (II), (IV), (VI), and (VIII); furthermore, (IX) is obtained from the corresponding 4‐acetoxyphenol (yield 87%).

Carbon–carbon bond formation by intramolecular 1,4-dipolar cycloaddition: heterocyclic betaines generated in situ from amides and N-substituted amides

Reaction of benzamides and N-substituted benzamides with appropriate o-alkenyl and -alkynyl side-chains and (chlorocarbonyl)phenyl ketene gives transient anhydro-1,3-oxazinium hydroxides which readily undergo intramolecular 1,4-dipolar cycloaddition; loss of CO2 from these 1:1-cycloadducts, isolable with N-substituted systems and alkenyl side-chains, gives chromeno[4,3-b]pyridin-2-ones.

New Nematic Liquid Crystals: Influence of Rigid Cored, Alkenyl Side-Chains and Polarity on Material and Display Properties

Abstract From the design of non-polar molecular structures exhibiting different rigid cores and isolated C=C double bonds in different side-chain positions and from investigations into the static dielectric birefringence, viscous, and all three elastic constants k 1, k 2, k 3, new, negative dielectric anisotropic nenatic liqueid crystals result, namely apolar alkenyls, which are shown to cover a wide range of materail porpertie, including large twist constants k 2. The combination of double bonds in 4-position, with rigid cores comprising heterocyclic rings is shown to lead to exceptionally low elastic rations k 3/k 1 ∼ 0.4 with simultaeoulsy low optical anisotropies and low roatational viscosities γ1. Moreover, laterally substituted alkenyls are shown to exhibit large negative dielectric anisotropies rendering them applicable for low viscous, positive contrasat guest-host mixtures with high order parameters 0.72≤ S ≤ 0.78. The stability of the new nematics comprising isolated double bonds is shown to be ...

The cooperative effects of heterocycles, NCS-polar groups, and double bonds on the material properties of new nematic liquid crystals

Eight new classes of positive dielectric anisotropic liquid crystals with polar NCS and CN end groups, comprising alkyl as well as alkenyl side-chains are presented. The isothiocyanates (NCS compounds) exhibit low bulk viscosities η(22°C) ∼ 11 cP as well as low rotational viscosities γ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> . The latter are up to 35 percent lower than those of structurally comparable CN compounds. We show that nematics with elastic ratios as low as <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k_{3}/k_{1} = 0.6</tex> result when combining suitable heterocyclic rings with four alkenyls and/or NCS groups. These unusually low <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k_{3}/k_{1}</tex> ratios as well as the low elastic expression <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">K = k_{1} + (k_{3} - 2k_{2})/4</tex> , combined with their large dielectric anisotropies Δε ∼ 20, render the compounds applicable for highly multiplexable low-threshold liquid-crystal displays. From numerical calculations, 160:1 multiplex ratios of TN-LCD's with a contrast of 5:1 appear feasible. While the new compounds reduce the low end of the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k_{3}/k_{1}</tex> range of positive dielectric nematics by ∼40 percent, thus improving the multiplexibility of TN-LCD's considerably, it is shown that supertwist birefringence mixtures comprising three alkenyls exhibit rather large <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k_{3}/ k_{1}</tex> ratios. An SBE mixture is presented that leads to multiplexing ratios exceeding 400:1 at a contrast of at least 10:1 between 0° and 50°C without external temperature compensation. The in situ temperature compensation is achieved by novel cholesteric additives.

Studies on intramolecular cycloaddition reactions of some isoquinolinium salts

Thermally-induced Intramolecular addition reactions of isoquinolinium derivatives bearing an alkenyl side-chain have been studied. Cycloadditions can occur across the isolated olefinic bond and the 1,4-positions of the isoquinolinium system to produce tetracyclic adducts. The chemistry of these adducts is compared with that of cyclo-adducts produced in intermolecular additions. Preparation of some of the isoquinoline derivatives involved alkylation of the parent base; 3-methylisoquinoline can be substituted either at the methyl group, upon reaction with aromatic nitrites or at C-4, using alkyl halides.

Lipid composition of SV40‐induced transplantable hamster tumor

The analysis of the lipid composition of the SV40-induced transplantable hamster tumor has shown that: (a) the total phospholipid content in the tumor is lower than that usually found in normal tissues and similar to that reported for other neoplasms; (b) except for a lower percentage of diphosphatidylglycerol, the phospholipid composition is comparable with that reported for normal tissues; (c) the fatty acid profiles of the various glycerophospholipid classes are characterized by high proportions of oleic acid; and (d) phosphatidylethanolamine contains proportions of alkenyl side chains which are consistent with the amounts of plasmalogenic phospholipids found in other neoplasms.

Thermal electrocyclic ring closure of alkenylhexa-1,3,5-trienes and the question of anchimeric π-bond participation

The anomalously fast electrocyclic ring closure of 3-vinylhexa-1,3,5-triene to yield 2-vinylcyclohexa-1,3-diene had previously been interpreted as involving anchimeric π-bond participation of the 3-vinyl group in the electrocyclization transition state. In order to determine whether this observation and interpretation was indeed characteristic of alkenyl side-chains, 3-allylhexa-1,3,5-triene and 3-propylhexa-1,3,5-trienes were synthesized and their electrocyclization rates and activation parameters compared both to each other and to the corresponding 3-ethyl and 3-vinyl trienes. The results conclusively show that the accelerative effect operative in 3-vinylhexa-1,3,5-triene ring closure does not extend to non-conjugated alkenyl side chains.

Isomerisation of 2-(alkenyl)pyridines by Group 6 metals

Reactions of 2-(alkenyl)pyridines with Group 6A hexacarbonyls and [M(CO)4(nbd)](M = Cr, Mo, or W; nbd = norbornadiene) are described. Isomerisation of the alkenyl side chain occurs with 2-(CR1MeCR2)-, 2-(CH2CR1CH2CH2)- and 2-(CH2CHCH2CH2CH2)-C5H4N (R1, R2= H or Me) to give complexes of the type [M(CO)4L][L = 2-(prop-2′-enyl)- or 2-(substituted prop-2′-enyl)-pyridine] which have, in some cases, also been prepared directly from L; L is always bidentate. The mechanism of isomerisation is discussed. Spectroscopic studies provide no evidence for conformational isomerism involving the plane of the co-ordinated olefin. Related reactions with Ph2P[CH2]2CHCH2 and Ph2P[CH2]3CHCH2 give [Mo(CO)4(Ph2PCH2CH2CHCH2)] and [Mo(CO)4(Ph2PCH2CH2CH2CHCH2)2] respectively.

Separation and structural determination of the olefinic components of poison ivy urushiol, cardanol and cardol.

THE noxious saps of numerous members of the Anacardiaceae, such as Japanese lac, poison ivy, cashew nut shell liquid, etc., contain phenolic bodies carrying long unsaturated side-chains attached to the benzene ring. Earlier investigators1 have in certain cases established the length and the position of these alkenyl side-chains; but prior to the present investigation only very limited information was available concerning the structural details of the unsaturation. There is no doubt, however, that the unsaturation in the side-chain plays an important part both in the physiological properties2 and industrial uses3 of these compounds.