| 摘要 |
In the present invention, there are disclosed spermin-type lipopolyamines of the general formula I, in which X represents a bond between a carbon atom of the CO terminus group of the hydrophobic domain Y and a polyamine moiety nitrogen atom, or aminopolyethyleneglycol carboxamide coupling of the general formula II, in which ni1 = 1 to 13, or {omega}-hydroxy-alkylcarboxamide coupling of the general formula III, wherein ni2 = 1 to 9, or {omega}-hydroxyalkyl carboxamide polyethyleneglycol carboxamide coupling of the general formula IV, wherein ni3 = 1 to 9 and ni4 = 1 to 13, and the hydrophobic domain Y is in position C(2) symmetrically branched acyl of the general formula V, wherein ni5 = 5 to 30, or (3{beta})-cholest-5-en-3-yl of the general formula VI. Provided , X represents a bond between the carbon atom of the CO terminus group of the hydrophobic domain and the polyamine moiety nitrogen atom, or the aminopolyethyleneglycol carboxamide coupling of the general formula II, then Y is in position of C(2) symmetrically branched acyl of the general formula V, and provided, the X represents {omega}-hydroxyalkyl carboxamide coupling of the general formula III or {omega}-hydroxyalkyl carboxamide polyethyleneglycol carboxamide coupling of the general formula IV, then the hydrophobic domain Y is (3{beta})-cholest-5-en-3-yl of the general formula VI. There is also disclosed a process for preparing the lipopolyamines of the general formula I by converting symmetrically branched in position C(2) fatty acid of the general formula VII, in which ni1 = 5 to 30, or the acid of the general formula VIII, in which ni1 = 1 to 13 and ni5 = 5 to 30, or the acid of the general formula IX, in which ni2 = 1 to 9, or the acid of the general formula X, wherein ni3 = 1 to 9 and ni4 = 1 to 13, by reacting thereof with bis(pentafluorophenyl)carbonate in the presence of an organic base in a polar aprotic solvent to pentafluorophenyl esters, which are then converted by reacting with Ne2Ne3Ne4-tri-(tert-butoxycarbonyl)spermin in the presence of an organic base ion an organic aprotic solvent to protected polycationic lipids of the general formula XI. Also disclosed is the use of the polycationic lipids of the general formula I when constructing polycationic systems, i.e. polycationic liposomes as carriers of medicaments based on negative charged fragments of nucleic acids, i.e. nucleotide and oligonucleotide therapeutics and therapeutic gene constructs. |
