Editing Synthesis Lipophilic Polyamines (section)

=== Preparation of guanidino spermidine cholesterol BGSC <br><br>  ===

'''Preparation of the Di-Boc Carbamate (1)''' 

A solution of cholesteryl chloroformate (0.9 g, 2 mmol) and triethylamine (0.214 g, 2 mmol) in CH2Cl2 (40 ml) is added to a solution of 1N,8N-Boc2-spermidine (0.690 g, 2 mmol) in CH2Cl2 (20 ml). After refluxing for 5 hours, the mixture is washed with water (2×50 ml), dried over Na2SO4 and the solvent is evaporated off. The crude product is purified by chromatography on a silica gel using CH2Cl2/MeOH 95/5 as eluent to give pure carbamate 

<br>'''2. Preparation of the Aminocarbamate (2)''' 

Compound (1) (1.3 g) is dissolved in 20 ml of CH2Cl2 and 2 ml of freshly distilled Trifluoroacetic acid (CF3CO2H) are added to this cooled solution (ice bed) in order to release the protective BOC groups. After stirring at room temperature for 3 hours, 50 ml of 1N NaOH are added and the mixture is extracted with CH2Cl2 The organic layers are washed with water, dried over Na2SO4 and evaporated so as to obtain the crude aminocarbamate (2) (0.945 g, 98%). 

The crude carbamate (2) (0.94 g) is dissolved in 30 ml of the Tetrahydrofuran(THF)/MeOH 85/15. Next, 1H-pyrazolecarboxamidine (0.495 g, 3.4 mmol) and diisopropylethylamine (0.436, 3.4 mmol) in 30 ml of Tetrahydrofuran(THF)/MeOH 85/15 are added. After stirring at room temperature for 18 hours, 250 ml of diethyl ether are slowly added and the precipitate obtained is separated by decantation. The crude compound is suspended three times in diethyl ether and separated by decantation to give pure GSC (0.570 g, 47%).