By Gould R.F. (ed.)
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Partially-convergent strategies have been applied for the synthesis of unsymmetrical PAMAM dendrimers by reaction of divergently-synthesised PAMAM dendrons either via a 1,3-dipolar cycloaddition reaction [205, 206] or through a poly(ethyleneglycol) (PEG) core . In particular the PAMAM–PEG–PAMAM dendrimer showed high transfection efficiency, probably due to enhanced branch flexibility and DNA complexation . 0 Fig. 21 Synthesis of poly(L-lysine) dendrimers been used for the preparation of PAMAM dendrimers , this has not been employed in synthesising PAMAM-based transfection vectors.
5a) or synthesising the cationic lipid domain first and then linking two of these through a spacer at the end of the synthetic route  (see Fig. 5b). Aryl groups have been used as rigid spacers between the lipophilic groups and the cationic moieties [84, 111, 112] (see Fig. 5b). g. pyridine, imidazole, quinoline) have additionally been employed as headgroups of cationic lipids, in part because charge delocalisation is considered to diminish cellular toxicity [100, 113–125]. Among nitrogen-based heterocycles, quaternary pyridinium salts are the most widely used for the preparation of cationic lipids [118–125], being synthesised by quaternisation of the nitrogen atom [118–122] (see Fig.
23). PAMAM dendrons were assembled by treating deprotected scaffold-bound resin 24 first with an excess of methyl acrylate H N H 2N NH 2 O O Cl3 CH N O O O O O O O HN N O O O O N NO 2 2 2 O 1M NaOH:dioxane O Et3 N, CH 3 CN, 60°C O O N O O O O H 2N N O NH O 2 DIC, HOBt, DCM OH N O NH 2 2 O O O N H (24) Fig. 23 The synthesis of polyamine-bound resin 24 2 NH 2NH 2 H2 O EtOH, reflux O O N O O O O N O OH O N H 40 A. Unciti-Broceta et al. 0 (Base) NH O NH NH2 Fig. 24 Solid-phase synthesis of a G3 PAMAM dendrimer (1,4-addition) and then by reaction of the methyl ester with 1,3-propanediamine (see Fig.