Editing Synthesis Lipophilic Polyamines (section)

== TRENL for siRNA<br>  ==

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374058/<br> 

<br> 

[[Image:TRENL2.png]] 

<br> 

[[Image:TRENL1.png]] 

Cholesterol, 

oleic acid, <br>[[Image:Oleic acid.GIF]]<br> 

linoleic acid<br> 

[[Image:Linoleic acid.gif]]<br> 

<br> 

and linolenic acid,<br> 

[[Image:Linolenic acid.png]] 

tris(2-aminoethyl)amine (TREN) and 95% sodium hydride: Sigma-Aldrich (St. Louis, MO). 

(1,2-Dimyristoyl-sn-glycerol, methoxypolyethylene Glycol) (DMG-PEG):&nbsp;&nbsp; NOF America Corporation (White Plains, NY). 

Alkyl mesylates: Nu-Chek Prep, Inc. (Elysian, MN, USA).<br> 

mesylate: 

[[Image:Mesylate.png]] 

Oleyl Mesylate:&nbsp; http://www.trc-canada.com/detail.php?CatNum=O532965, 1g For $150(US)<br> 

[[Image:Oleyl Mesylate.png]]<br> 

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374058/figure/F1/ Synthesis] 

TREN is first alkylated by linoleic mesylate (LM) at different TREN:LM ratios, and the remaining amines of TREN can be methylated by a mixture of formic acid (HCOOH) and formaldehyde (HCHO) to obtain TRENL series lipids. <br> 

Add linoleyl mesylate (3.1g, 9 mmol) and 95% sodium hydride (0.075 g, 3 mmol) to a solution of TREN (0.44 g, 3 mmol) in 15 mL anhydrous chloroform.<br> 

Stir the mixture on a hot plate at 60°C for 12 h under nitrogen.<br> 

Cool the reaction mixture in an ice bath.<br> 

Add&nbsp; ethanol slowly. <br> 

Spin the reaction mixture at 2000 rpm for 5 min. <br> 

Transfer the organic phase&nbsp; to a new flask and evaporate under vacuum. <br> 

Dissolve the crude product of TREN-LM (1:3) in ethanol, filter to remove precipitates. <br> 

Add formic acid (2 g)&nbsp; add to a stirred aqueous solution of 1.5 g of TREN-LM (1:3) and 4 g of formaldehyde for 5 min in an ice bath. <br> 

Reflux under nitrogen for 24 h. <br> 

After cooling, the reaction mixture is neutralized by NaOH (10 N)<br> 

Wash twice using 30 ml of ethyl acetate.<br> 

Discard the aqueous layer and the organic phase is dried over magnesium sulfate at room temperature for 2 h.<br> 

Concentrate organic phase by rotary evaporation under vacuum. <br> 

Dissolve the oily residue in ethanol and evaporate again to get the final product TRENL3<br>