Cholesteryl chloroformate

Our laboratory mostly works with PEG-cholesterol. It is easily obtained in one step by addition of cholesteryl chloroformate and amino-methoxy-PEG (31). Introduction of a linker between the cholesterol and the PEG part would induce higher membrane fluidity and reduce more efficiently protein interactions as compared to PEG-cholesterol. A diaminobutane spacer was shown to improve significantly the sustained release of calcein from lipoplexes incubated in 30% serum (32). The spacer effect on bicatenar PEG-lipid has not been intensively studied because it can be expected that it would induce less effect on PEG-dioleoyl than on PEG-cholesterol, the lipidic anchor being predominant in the bilayer stabilization (Fig. 2). 

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). 

L-a-Dioleoyl Phosphatidylethanolamine (DOPE), and 1,2-Dipalmitoyl-OT-Glycero-3-Phosphocholine (DPPC) were purchased from Avanti Polar Lipids. The chol-PEGjj was obtained in one step from the reaction of cholesteryl chloroformate and a-amino-co-methoxy-PEG. The luciferase encoding gene was obtained as reported (22). Picogreen was purchased from Molecular Probes, USA, Baftlomycin from Sigma, France, the BCA kit from Pierce and the luciferase kit from Promega. 

Allylic alcohols Dimethylacetamide diethyl acetal. p-PhenylsuIfonylbenzoylchloride. Amines Carbobenzoxy chloride. Cholesteryl chloroformate. 2,4-Dinitrobenzaldehyde. Di-p-toluyl-D-tartrate. Ethylene sulfide. N-Hydroxymethylphthalamide. Oxalic acid. 

Cholesteryl chloroformate (10.11) is produced [1125] from reaction of cholesterol and... 

Dissolve cholesteryl chloroformate (7.5 g, 17 mmol) in 40 mL of THF and add this solution to the dropping funnel. Close the dropping funnel with a second guard tube (alternatively use a stoppered pressure-equalizing dropping funnel). 

To the dropping funnel, add a solution of cholesteryl chloroformate (18.0 g, 40 mmol) in dichloromethane. Add the solution of cholesteryl chloroformate drop-wise to the contents ofthe round-bottomed flask. 

Cholesteryl 4-vinylphenyl carbonate was synthesized by reacting 4-vinylphenol (obtained by hydrolyzing 4-acetoxystyrene) and cholesteryl chloroformate (commercially available) in dry THF. To the mixture of this carbonate ester (5 mol%) and ethylene glycol dimethacrylate (95 mol%) in hexane (2 mL/g, solvent/monomers), was added AIBN (1 mol% with respect to the C=C bonds). The solution was degassed and sealed at a reduced pressure. The polymerization was carried out at 65 °C for 24 h. The resulting polymer was washed with methanol, ground (average size 30 pm), extracted with methanol in a Soxhlet apparatus for 12-18 h, and dried in vacuo. In order to hydrolyze the carbonate esters, the polymer particles were suspended in 1 M NaOH/ methanol. After the suspension was refluxed for 6 h, it was added to dilute hydrochloric acid and filtered. The polymer was further washed with water, methanol, and ether, extracted with methanol and then with hexane, and finally dried in vacuo [3]. 

Cholesteryl chloroformate AnhydrousTHF Anhydrous triethylamine 2,6 -di- tert-butyl- 4 -methyl-phenol (BHT)... 

Copolymers with amorphous A block and liquid crystalline B block have been synthesized. The hydroboration of polybutadiene or butadiene styrene block copolymer with 9-BBN yields the intermediate, which on oxidation, followed by esterification with cholesteryl chloroformate, leads to the formation [4] of the said polymer. 

The hydrosilylation-allylation protocol is applicable to the syntheses of dendritic polyols . The hydroboration-oxidation of G0-G3 dendrimers prepared in accordance with the synthetic routes shown in Scheme 24 give the corresponding dendritic polyols, GO-OH-G3-OH, which are characterized by H NMR and MALDI-TOF analyses. Further modifications of the dendritic polyols with cholesteryl chloroformate yield unique dendrimers possessing 12, 36 and 108 cholesteryl units, providing the first examples of flexible dendrimers substituted with rigid mesogenic units that are expected to have unusual liquid crystalline properties . The second generation polyol dendrimer 264... 

Cholesterol has also been coupled to polymer chain ends after other chemical modifications on its OH position. The most-reported method uses cholesteryl chloroformate (CholCl), which is commercially available, to react with OH or NH2 end-functionaMzed polymers (i.e., PEG [118, 119] and polyacrylamide derivatives [120, 121]). Quantitative functionalization can be achieved with either 1 equiv. or... 

Cholesteryl chloroformate added at 35° to Nal in acetone followed by sufficient ether to make the soln. homogeneous, and the product isolated after 70 hrs. 

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