Dendrimers divergent growth approach

Scheme 22. a) The divergent growth approach for the preparation of dendritic polyesters. b) The divergent approach for the preparation of dendrimer having 16-hydroxy groups... 

Scheme 30.18 Accelerated synthesis of a fourth-generation bis-MPA dendrimer using CuAAC click coupling reactions in combination with esterification chemistry by the divergent growth approach. Reproduced with permission from Ref [132] 2007, The Royal Society of Chemistry.

Scheme 30.19 The rapid synthesis of a sixth-generation dendrimer using an orthogonal AB2 — CD2 divergent growth approach employing both thiol-ene and CuAAC click coupling reactions, (i) Thiol-ene coupling (ii) CuAAC (iii) Thiol-ene coupling (iv) CuAAC (v) Thiol-ene coupling (vi) CuAAC. Reproduced with permission from Ref [133] 2010, American Chemical Society.

The first and still dominant route to synthesize PAMAM dendrimers is via the divergent growth approach as reported by Tomalia etal in 1985. It involves a Michael addition reaction between a core, comprising primary amines, and an excess of methyl acrylate (Figure 17). Once the reaction has reached completion, an aminolysis step of the methyl esters with an excess of a-alkanediamines yields the first-generation PAMAM... 

In 1989, Fr chet and co-workers first reported the convergent growth approach [8,9]. In contrast to the divergent growth approach, dendrimer construction is initiated at what will eventually become the outer surface shell of the ideally branched macromolecule and proceeds inward, by a stepwise addition of branching monomers, followed by the final attachment of each branched dendritic sub-unit (or dendron ) to a poly-functional core. This synthesis generated a poly(aromatic ether) dendrimer and a repetitive sequence of Williamson ether coupling and bromination reactions were employed as shown in Scheme 8.1. 

Launay N, Caminade AM, Majoral JP (1995) Synthesis and reactivity of unusual phosphoms dendrimers—a useful divergent growth approach up to the 7th generation. J Am Chem Soc 117 3282-3283... 

Dendrimers produced by divergent or convergent methods are nearly perfectly branched with great structural precision. However, the multistep synthesis of dendrimers can be expensive and time consuming. The treelike structure of dendrimers can be approached through a one-step synthetic methodology.31 The step-growth polymerization of ABx-type monomers, particularly AB2, results in a randomly branched macromolecule referred to as hyperbranch polymers. 

The convergent growth approach to dendrimers [1] first introduced [2] in 1989 at the IUPAC meeting on macromolecules in Seoul, Korea, has provided a useful alternative to the divergent methods exemplified by the work of Tomalia et al. on PAMAM dendrimers [3] and Meijer et al. on polypropylene imine) dendrimers [4], Today several hundred papers have exploited the convergent approach to dendrimers to prepare a variety of synthetic functional macromolecules of unparalleled structural precision. 

The near monodispersity typically associated with dendrimers prepared by both the divergent or convergent growth approaches presents a number of interesting characterization traits when compared to traditional narrow polydisper-sity linear polymers. These features are further enhanced by the high degree of symmetry normally associated with dendritic macromolecules and permit an unprecedented amount of structural information to be obtained using standard characterization techniques. 

More recently an interesting dendron construction method was reported independently by Frechet et al. [102] as well as by Neenan and Miller [103] which has been referred to as the 1(B) Convergent Method. This method differs from the divergent dendron approach in that exponential proliferation of surface groups is accomplished by use of a limited number of growth reactions per sequence. Its advantages and limitation will be discussed later. With this method a variety of dendron families have been successfully synthesized and subsequently coupled to various point-like as well as hyper-branched cores, to produce dendrimers. This... 

Dendritic layer copolymers have also been prepared via the hypercore approach,87 and by divergent growth from the periphery of convergently prepared dendrimers,446 or dendronized polymers.398 This layered dendritic architecture has been used by a number of groups to probe the nature of chirality. 

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