Heptyl Side Chain Research Articles

Biocatalyzed Reactions towards Functional Food Components 4-Alkylcatechols and Their Analogues

Catechols are antioxidants and radical scavengers with a broad medical potential. 4-Methylcatechol (1b) and 4-ethylcatechol (2b) (occurring in some traditional fermented and smoked foods) activate the cell defense against oxidative stress. We examined the biocatalyzed reactions towards 4-n-alkylcatechols with different side chains length, which is a factor important for the biological activities of catechols. 4-n-Alkylcatechols with methyl through heptyl side chains (1b–7b) were obtained in one pot by (i) oxidation of phenols 1a–7a with tyrosinase from Agaricus bisporus followed by (ii) reduction of ortho-quinones (intermediates) with L-ascorbic acid sodium salt. The conversions decreased with increasing side chain length. The preparative reactions were carried out with substrates 1a–5a. The isolated yields of the purified products decreased from 59% in 2b to 10% in 5b in correlation with logP of the substrates. Homology modeling indicated that the affinities of two tyrosinase isoforms (PPO3 and PPO4) to the substrates with side chains longer than C2 decreased with increasing side chain length. This was probably due to steric limitations and to missing interactions of the extended side chains in the active sites. We envisage using the model to predict further substrates of tyrosinase and testing the products, catechols, for radical-scavenging and biological activities.

π-Conjugated polymers with pendant coumarins: design, synthesis, characterization, and interactions with carbon nanotubes

A series of new fluorene-based π-conjugated polymers having coumarin derivatives as part of dendritic side chains were designed and prepared using the Suzuki–Miyaura cross-coupling reaction. A new coumarin derivative bearing a heptyl side chain for solubility was utilized to ensure solubility of the final polymers. It was found that fluorescence resonance energy transfer (FRET) from the coumrains to the polyfluorene backbone was efficient, especially for the polymers decorated with lower-generation dendrons. Each of the polymers was found to interact strongly with the surface of single-walled carbon nanotubes (SWNTs) in THF, and their ability to selectively disperse specific SWNT chiralities was investigated. Photoluminescence studies revealed that the strong polymer emission is efficiently quenched in the corresponding supramolecular complexes with SWNTs. This high quenching efficiency indicates that the coumarin–polymer FRET system can be supramolecularly bound to the surface of (SWNTs to produce an energy transfer system in which the energy absorbed by the donor coumarin chromophores is channeled to the SWNTs.

Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent

Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy. These results suggest a promising strategy for developing novel sodium channel inhibitors with imaging capabilities.

Study of unsymmetrical dimesogens containing 4‐heptylazobenzene

Abstract4‐Heptylazobenzene (HAB) has been covalently attached to cholesterol (Ch) by varying the methylene spacers and to cyanobiphenyl (CB) moiety with an octyl methylene linkage. Enhancement of short‐range translational correlations in the chiral nematic (N*) phase has been observed by the introduction of HAB moiety. HAB–Ch dimesogens exhibit chiral smectic C (SmC*), chiral smectic A (SmA*) and N* phases depending on the methylene spacer length. The dimesogen containing HAB–CB shows a SmA and an N phase. The HAB–Ch dimesogen with octyl methylene spacer shows co‐existence of multiple periodicities in its SmA* as well as in SmC* phases. A dramatic increase of >150 nm in the N* reflected wavelength shift (Δλ) with change in temperature has been observed for the HAB‐Ch dimesogen containing an octyl spacer compared to the similar dimesogen that does not have a heptyl side chain. Ferroelectric switching has been studied for a representative dimesogen containing HAB‐Ch having hexyl spacer in its SmC* phase, the spontaneous polarization value was determined to be 150 nC cm−2 (at 125 °C) by applying a triangular wave field. A reversible photochemical switching between SmA and N phases also has been reported for the dimesogen containing HAB–CB. Copyright © 2007 John Wiley & Sons, Ltd.

Identification by flow cytometry of seiridin, one of the main phytotoxins produced by three Seiridium species pathogenic to cypress.

Seiridin (SE), one of the main phytotoxins produced in vitro by Seiridium species pathogenic to cypress, was oxidized and the corresponding ketone derivative covalently linked to bovine serum albumin (BSA). The conjugate (SE-BSA) was used to prepare an antiserum to SE. The antibodies were absorbed with BSA and their specificity was assayed by ELISA and flow cytometry against SE, iso-seiridin (ISE), a structural isomer of SE, and some derivatives of these two metabolites. The antibodies tested in a competitive indirect ELISA did not show any binding activity to SE, ISE and their derivatives. The cytometry test, instead, was successful. SE-BSA and SE showed the highest binding activity with the antibodies. SE derivatives having a shift on the adjacent carbon, oxidation, or acetylation of the hydroxy group of the heptyl side chain at C-4 or conversion of the gamma-lactone in the corresponding planar furane ring reacted less than SE. The 2'-dansylhydrazoneSE and the 3,4-dihydroSE having a bulky group attached to the heptyl side chain and a saturated lactone ring, respectively, showed a weak reactivity. SE derivatives in which the gamma-lactone ring was destroyed and ISE derivatives presenting the shift of the hydroxy group at C-3' and another structural modification had no binding activity.

Synthesis of homoceramides, novel ceramide analogues, and their lack of effect on the growth of hippocampal neurons.

The synthesis of a new series of D-erythro-homoceramide analogues is described. Several synthetic approaches were investigated. Homoceramides can be successfully synthesized from L-homoserine as chiral building block and a protected Weinreb-amide as a key intermediate. The synthesis of short-chain analogues with a heptyl side chain, as well as with a phenyl residue in the sphingoid part (instead of the naturally occurring tridecyl side chain), was effected. The homoceramides 15-17 and 24 were investigated for their potential to reverse the inhibitory effect of fumonisin B(1) on axonal growth. Unfortunately, none of the tested compounds showed any biological activity due to their lack of metabolism to glucosylhomoceramide.

Progress toward the development of a safe and effective agent for treating reentrant cardiac arrhythmias: synthesis and evaluation of ibutilide analogues with enhanced metabolic stability and diminished proarrhythmic potential.

A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

Indoloquinones, part 5. Palladium-catalyzed total synthesis of the potent lipid peroxidation inhibitor carbazoquinocin C

The efficient palladium-catalyzed oxidative coupling of an anilinoquinone and subsequent regioselective introduction of the heptyl side chain provide the antioxidative substance carbazoquinocin C in four steps and 36% overall yield from aniline.

Structural study of monolayers of alkyl side chain substituted polyimides

Monolayers of alkyl side chain substituted preformed polyimides (BACBP/BPDA) exhibit behaviour different from that of other `hairy-rod' polymers which were studied previously. This behaviour is thought to arise from the extreme rigidity of the backbone as well as the particular way in which the alkyl side chains extend from the biphenyl unit. These soluble polyimides can form metastable monolayers for which the pressure-area isotherms vary markedly with side chain length. This side chain length dependence suggests that the side chains can not readily project away from the water surface, but rather occupy considerable space at the interface at lower temperatures. For the polyimide with octadecyl side chains, a sharp reduction in zero pressure area occurs between 20 and 24°C, suggesting an important change in side chain mobility, while the polyimide with heptyl side chains shows no strong dependence of zero pressure area on temperature. These materials are promising for creating robust molecularly thin layers.

Studies on structure-activity relationship of seiridins, phytotoxins, produced by three species of Seiridium.

The phytotoxins seiridin (SEI) and iso-seiridin (ISE), two delta alpha,beta-butenolides produced in vitro by Seiridium cardinale, S. cupressi, and S. unicorne, as well as their derivatives obtained by chemical modification of each toxin, were analyzed for their bioactivity. The effects each compound on host and non-host plants and their antimicrobial activity on bacteria were investigated. The toxicity of both seiridins (SEIs) decreased in the derivatives with modifications of the gamma-lactone ring or with acetylation of the hydroxy group of the aliphatic side chain at C-4. Shoot tissues of Cupressus macrocarpa artificially infected by S. cardinale leached electrolytes more than those of C. sempervirens and C. arizonica. Electrolyte loss from shoot tissues of cypress plants treated with each derivative also decreased for most of them. Seed germination was not affected by SEI and ISE derivatives. Inhibition of root growth of three herbaceous test plants was studied. SEI and 3,4-dihydro SEI were active to germlings of lettuce. No ISE derivative affected root growth of lettuce and oat germlings. Reduction was observed on roots of radish germlings treated with acetyl ISE or 3,4-dihydro ISE. No derivative of SEI or ISE elicited hormone-like activity as SEI did. Antibacterial activity shown by SEI and ISE at 150 microM accounted for both hydrogenated derivatives of SEI. The integrity of the delta alpha,beta-unsaturated-gamma-lactone ring and the location of the hydroxy group in the heptyl side chain are features of importance in biological activity of the two butenolides.

New Applications of Crown Ethers. X. 13C NMR Relaxation Times Study of Cation-Binding Behavior of Monoazacrown Ethers and Bis(monoazacrown ether)s

Abstract 13C NMR relaxation times (T1s) have been determined for monoazacrown ethers (CA15C5 and CA18C6) and bis(monoazacrown ether)s (BCA15C5, BCA18C6, BOA15C5, and BOA18C6) in the absence and presence of Na+and K+ ions. For the monoazacrown ethers with heptyl side chain and the bis(monoazacrown ether)s with pentamethylene bridge chain marked changes in T1 values are observed upon the complexation, and the changes are dependent on the cation and on the structure of the ligands. The complexation with Na+ ion can give a larger effect on the T1 values for the bis(monoazacrown ether)s of 15- and 18-membered rings, especially on the mobility of the bridging chain carbons, which is indicative of the formation of an intramolecular sandwich complex. On the other hand, the present T1 study again shows the prominent effect of the oxygen in the bridging chain on the complexation of BOA15C5 and BOA18C6. Small differences in T1 values obtained between Na+ complexes and K+ complexes of these two bis(crown ether)s suggest that the complexes take an analogous partial structure for the two cations.