Cholesteryl cation

The displacement of homoallylic tosylates follows an entirely different course with a strong tendency for the formation of cyclo steroids. Thus, when the 3/ -tosylate of a A -steroid (187) is treated with lithium aluminum deuteride, the product consists mainly of a 3l3-di-A -steroid (188) and a 6c-dj-3,5a-cyclo steroid (189). The incorporation of deuterium at the 3 -position in (188) indicates that this reaction proceeds via a 3,5-cyclo cholesteryl cation instead of the usual S, 2 type displacement sequence. This is further substantiated by the formation of the cyclo steroid (189) in which the deuterium at C-6 is probably in the p configuration. ... 

The term homoconjugation (a through-space interaction of orbitals) was introduced by Winstein and Adams (1948) in connection with the cholesteryl cation [1]. Applequist and Roberts (1956) were the first to progress to the concept of homoaromaticity in considering the homocyclopropenium cation [2], Soon after this Doering et al. (1956) invoked pseudoaromatic ... 

We may consider the formation of the mesomeric cholesteryl cation to be a case of w-bond participation in solvolysis of the C 3> tosylate well before the transition state is reached. The process is best pictured in terms of overlap between the atomic -orbital at C(S) and the a-lobe of the electron-deficient orbital at C(3) (6). The effectiveness of orbital overlap is altered by various structural changes in a qualitatively predictable manner, as revealed by reaction rates, including those in Table 21. Another example is provided by B-nor-cholesteryl tosylate [2y], which reacts at only half the rate of cholesteryl tosylate.. The effect of the contracted ring B is to flatten the... 

The structure (2) commonly written for the cholesteryl cation is adequate to explain the observations mentioned so far, but further refinements to the detailed structure must now be considered. Winstein, in 1956 [35], discussed the alternative formulations A, B and C, as possible contributors to the mesomeric cation ... 

Miscellaneous Rearrangements.—Solvolysis rates for cholesteryl tosylate in different solvents show an excellent correlation with rates for cyclopropyl-carbinyl tosylate, indicating similarity of mechanism. Two distinct correlation curves were obtained, depending upon solvent classification. Stereoelectronic restrictions in the cholesteryl cation permit only a single structure for charge dispersal between positions C-3, C-5, and C-6, but several non-classical structures seem plausible for the cyclopropylcarbinyl cation. It is suggested that two such structures, depending upon solvent character, may account for the observation of two correlation curves. 

Cholesteryl myristate [1989-52-2] M 597.0. Crystd from n-pentanol. Purified by column chromatography with MeOH and evaporated to dryness. Dissolved in water and ppted with HCI (spot 1) or passed through a cation-exchange column (spot 2). Finally, dried in vacuum over P2O5. [Malanik and Malat Anal Chim Acta 76 464 7975]. 

J. D. Roberts,seems to have first used the term nonclassical ion when he proposed the tricyclobutonium ion structure for the cyclopropylcarbinyl cation. See J. D. Roberts and R. H. Mazur, J. Am. Chem. Soc. 73, 3542 (1951). Winstein referred to the nonclassical structure of norbornyl, cholesteryl, and 3-phenyl-2-butyl cations. See S. Winstein and D. 

In a subsequent study [30], cholesteryl-substituted 18C6 derivative 11 and diaza [18]crown-6 12 (Scheme 6) were used to create solid-supported bilayer lipids. The liquid crystalline crown derivatives 11,12 were dissolved in chloroform and mixed with squalene or squalene saturated with cholesterol. The solid-supported bilayers were prepared in freshly cut stainless steel wires. A 10-4 to 10-1 mol L-1 solution of MCI (M = Li, Na, K, Rb, Cs) or MgCl2 was used as aqueous phase. Measurement of the membrane potential revealed a Nemst response to the concentration of M+ in solution. It was possible to differentiate between the different cations which might be used for the preparation of new ion sensors. For the detection of K+ and Rb+, aza crown derivative 12 proved to be the most selective. A problem was the presence of traces of Fe2+/3+ that made the measurements difficult. It was also not... 

A systematic analysis to determine the biophysical characteristics of some cationic lipid/DNA complexes from this series was undertaken (Eastman et al., 1997). Product 1 (Figure 15.7) is currently being used in clinical trials as a carrier of CFTR gene in cystic fibrosis. The synthesis of these cholesteryl derivatives is similar to that of DC-Chol cholesteryl chloroformate is reacted with spermine or spermidine as polycation (Lee et al., 1996). 

Ghosh YK, Visweswariah SS, Bhattacharya S (2000) Nature of linkage between the cationic headgroup and cholesteryl skeleton controls gene transfection efficiency. FEBS Lett 473 341-344... 

The concept of a stable mesomeric cation cannot be inferred solely from kinetic results, but follows from analysis of reaction products, and studies of the reactions of "i-cholesterol and its derivatives. Most important was the demonstration by Winstein [35] that identical product mixtures are produced by the methanolysis of either cholesteryl tosylate or 6 trichloroacetoxy-3a,5a-cyclocholestane (15 X O-COCCls), from which it was argued that these steroids solvolyse through a common cation. Furthermore i-cholesteryl methyl ether (15 X = OMe) is converted by absolute ethanol into a mixture of i-cholesteryl ethyl ether (15 X — OEt) and cholesteryl ethyl ether [36]. i-Cholesteryl acetate (15 ... 

As already stated (p. 240), sr-bond participation does not occur in the solvolysis of e f-cholesteryl tosylate (i). Whatever the reaction conditions the major product is cholesta-3,5 diene, probably resulting from a normal raws-diaxial elimination with the 4/6-proton. Powerfully nucleophilic reagents like pyridine may also give a little of the g/S-substituted product by an Sn2 process [34], A curious side-reaction observed during buffered methanolysis [y ] or hydrolysis [y6] of efi cholesteryl tosylate has been interpreted as a rearrangement of the classical C(S) carbonium ion (2) by hydride migration from C(4), to give the resonance-stabilised ylic cation (3). The structure of this cation was revealed when the methanoly-... 

The "symmetrical ion (B), corresponding most nearly to the accepted symmetrical structure of the cyclopropylcarbinyl or bicyclobutonium cation (4) [22], represents delocalisation of the 4,5-bonding electrons as well as the sr-electrons. In its extreme form, 4,5-bond delocalisation is represented by the "unsymmetrical structure (C). Recent work indicates that structures involving 4,5-bond delocalisation may be important. Whitham [43] found that cholesteryl tosylate and 3jS-hy-droxymethyi A-norcholest-5-ene tosylate i8) solvolyse in buffered aqueous acetone to give i-cholesterol and cholesterol... 

Homoallylic participation was first invoked by Shoppee to account for the high rates and the stereospecificity of 3/3-(415) and i-cholesteryl (416) interconversions339). The double bond in (415) is clearly restricted to participation by one end. We cannot distinguish, however, between a homoallylic and a cyclopropylcarbinyl cation as the intermediate [cf. (387) and (355)] because both would be chiral. The same limitations apply to the 3-cyclohexenyl system. The tosylate (417) acetolyzes slightly more slowly than cyclohexyl tosylate340). The products include the acetate (418) corresponding to the starting material, the bicyclic acetate (419), and (420) as a result of hydro-... 

Folate-targeted LPD-II particles were generated by mixing anionic liposomes composed of DOPE/cholesteryl hemisuccinate (CHEMS)/ folate-polyethyleneglycol (PEG)-DOPE and the cationic DNA-polylysine (1 0.75, w/w) complexes. Structural analysis of LPD-II by negative-stain EM showed that the DNA-polylysine (which appears individually as rod shaped) and lipid complex seemed to be a highly electron dense, spherical core with a low-density coating. The mean diameter of these particles was 74 14 nm, i.e., smaller than the empty liposomes. 

J. D. Roberts was the first to use the term nonclassical ion when he proposed the tricyclobutonium ion structure for the cyclopropylmethyl cation. Winstein referred to the nonclassical structure of norbomyl, cholesteryl, and... 

Studies of cells in culture have provided considerable information about the control of this pathway [97]. In early studies, cultured skin fibroblasts were maintained for 24 h in a medium containing lipoprotein-deficient serum. These cells showed increased binding of LDL to cell surface receptors and increased HMG-CoA reductase activity. When LDL were added to the medium, binding, uptake, and degradation of the LDL followed. LDL CE were hydrolyzed, and decreased levels of both HMG-CoA reductase and the apo B/E receptor were seen. Furthermore, increased formation of cholesteryl oleate could be demonstrated. In subsequent studies, modified LDL with a net positive charge were used. These cationized LDL were internalized by a mechanism that did not depend on the apo B/E receptor, and that led to a substantial increase in cell cholesterol [103]. Under these conditions there was again increased synthesis of cholesteryl oleate. These findings support two principal conclusions (1) plasma lipoprotein CE is an important source of cholesterol for fibroblasts and similar cells and (2) the formation of intracellular... 

Kunieda s group reported numerous viscoelastic worm-like micellar systems in the salt-free condition when a lipophilic nonionic surfactant such as short hydrophilic chain poly(oxyethylene) alkyl ether, C EOni, or N-hydroxyethyl-N-methylaUcanolamide, NMEA-n, was added to the dilute micellar solution of hydrophilic cationic (dodecyltrimethylammonium bromide, DTAB and hexade-cyltrimethylammonium bromide, CTAB) [12-14], anionic (sodium dodecyl sulfate, SDS [15, 16], sodium dodecyl trioxyethylene sulfate, SDES [17], and Gemini-type [18]) or nonionic (sucrose alkanoates, C SE [9, 19], polyoxyethylene cholesteryl ethers, ChEO [10, 20], polyoxyethylene phytosterol, PhyEO [11, 21] and polyoxyethylene sorbitan monooleate, Tween-80 [22]) surfactants. The mechanism of formation of these worm-Hke stmctures and the resulting rheological behavior of micellar solutions is discussed in this section based in some actual published and unpublished results, but conclusions can qualitatively be extended to aU the systems studied by Kunieda s group. 

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