Divergent syntheses

Synthesis of a dendrimer according to the divergent method (Fig. 2.1) proceeds stepwise starting from a multi-functionalised core building block, to whose reac- 

Dendrimer Chemistry. Fritz Vogtle, Gabriele Richardt and Nicole Werner Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32066-0 

An advantage of the divergent method - which was the first to be developed [1] - is the attainable high-molecular (nano)scaffold architecture as well as the possibility of automation of the repetitive steps. The divergent method is therefore the method of choice for - commercially available - POP AM and PAMAM dendrimers (see Section 4.1). 

One disadvantage of this synthetic methodology is seen in the exponentially increasing number of functional terminal groups (KxMn see Section 1.2), since they cannot always be made to react quantitatively and thus give rise to structural defects. Such defects cannot always be avoided, even on addition of large excesses of reactants. Moreover, purification and separation of structurally perfect from defective dendrimers are problematic because the compounds have very similar properties. 

The first known syntheses of dendritic molecules were divergent and were used by the working groups of Vogtle [1], Denkewalter [2], Tomalia [3], and Newkome [4], 

The choice of appropriate activating group for the carboxyUc acid function of the C(o building block 1 was the key to this synthesis. Effectively, the reaction conditions for the activation step may not be strongly acid or basic, to preserve the ester functions. Furthermore, the grafting onto the dendritic polyamines requires an extremely efficient reaction to obtain the corresponding functionaUzed derivatives with good yields and to avoid the formation of defective dendrimers. The prepara- 

Chemoselective reaction with a diamine followed by q anuric chloride in a subsequent step provides the next larger intermediate. Iteration leads to materials that can be dimerized. Dimerizing the molecule shown would provide a G2 dendrimer with eight end groups. 

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J.M.J. Frechet (C. J. Hawker, 1990) replaced the divergent synthesis by a convergent growth of a dendritic polymer. The repeatedly employed monomer, 5-hydroxymethyl-l, 3-benzenediol, was 1,3-O-dibenzylatcd with 3,5-bis(benzyloxy)benzyl bromide. The resulting benzyl alcohol containing 7 benzene rings was converted to the benzyl bromide which was... 

The first steps of a second process for divergent synthesis of dendritic polymers by ATRP are shown in Scheme 9.73.12S In this case, a caiixarcnc core... 

Scheme 10 Divergent synthesis of 2-amino-1,3,4-oxadiazoles and 2-sulfonamido-l,3,4-oxadiazoles...

A divergent synthesis of tropane alkaloid ferruginine was reported by Node and coworkers [59]. The P-ketoester intermediate was prepared by a novel PLE-catalyzed asymmetric dealkoxycarbonylation (hydrolysis followed by a decarboxylation) of a symmetric tropinone-type diester (Figure 6.12). Dimethyl sulfoxide was added to the phosphate buffer pH 8 (1 9) to reduce the activity of PLE and prevent over-deal-koxycarbonylation leading to tropinone. 

Scheme 13. Divergent synthesis of platinum-acetylide dendrimers...

Scheme 3.25 Improved efficiency through divergent synthesis.

Scheme 2. Tomalia s divergent synthesis of dendronized polyethylene imine (PEI)...

Keywords Macromolecules m Dendrimers m Fractal Structure m Hyperbranched Polymers m Nanostructure m Divergent Synthesis m Convergent Synthesis m Dendrylation... 

Dendritic growth hybrids are prepared using one or more functional groups of a preformed linear chain to effect the stepwise growth of one or more dendritic blocks via divergent synthesis. 

At the center of the dendrimer is the core that represents the first synthetic step in divergent synthesis, or the last step in convergent synthesis. Each concentric shell of branched units is a generation (X), designated (GX), of identical repeat units. Hundreds of chemical repeat units have been reported [3, 4], but our characterization has been focused primarily on poly(amidoamine) (PAMAM), -(CH2CH2CONHCH2CH2N) < [1], or poly(propyleneimine)... 

Tomalia, D. A. and Dvornic, P. R. Dendritic polymers, divergent synthesis (starburst polyamidoamine dendrimers) , in Salamone, J. C. (ed.), Polymeric Materials Encyclopedia, Vol. 3, CRC Press, Boca Raton, FL, 1996, pp. 1814-1830. 

We have recently developed a novel, highly efficient, divergent synthesis [25]... 

DIVERGENT SYNTHESIS OF PAMAM DENDRIMERS VIA EXCESS REAGENT METHOD PREPARATION OF ESTER TERMINATED PAMAM STAR-BRANCHED PRECURSOR [NH2-(CH2)2 6-NH21 (G = -0.5) STAR-PAMAMICO E) [1]... 

Scheme 3. Divergent synthesis of the polyphenylene dendrimers based on the Diels-Alder cycloaddition... 

For the divergent synthesis, the reaction sequence is amidification/chlorida-tion. Once the polychloride of the acid is obtained, a partial or total amidifica-tion reaction with an amino alcohol yields a MIM, which is either ionic or nonionic, respectively. 

Fig. 2-22 Divergent synthesis of PAMAM dendrimer. Generation is 1 for LXIV and 5 for LXV.

Goodman and co-workers177-3 have approached the divergent synthesis differently. In their syntheses of collagen models consisting of three copies of homomeric peptide chains, solid-phase schemes begin with monomers 44 and then the template, the Kemp tricarboxylic acid (KTA) 10,[80 is used to link three monomers, also on resin, to form the peptide dendrimers 46 via 45 (Scheme 12). 

Difficulties that have been encountered in divergent synthesis can be attributed to the clustered nature and sequences of peptide dendrimers that form interchain hydrogen bonds and occlude coupling reactions. Solvent combinations such as DMSO and NMP, as well as coupling at elevated temperatures (50-60 °C),[94] have been used to overcome these side reactions and should be used if a single coupling fails to complete the reaction. It is best not to dry the peptide resin at any stage of the synthesis because re-solvation of dried peptide dendrimer resin is difficult. 

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