A divergent route towards single-chemical entity triazine dendrimers with opportunities for structural diversity

Abstract

This manuscript describes the successful synthesis and characterization of five generations of dendrimers based on melamine. Early generations of these materials appear to be single chemical entities: upon purification, no detectable impurities are observed using NMR spectroscopy, mass spectrometry, and HPLC and GPC analysis. The analysis of larger generation materials precludes an unambiguous statement of purity. The synthetic route to these targets is divergent, relying on dichlorotriazine monomers that react with a polyamine dendrimer core of generation n to produce a poly(monochlorotriazine) dendrimer of generation n + 1. Subsequently, the poly (monochlorotriazine) is derivatized through nucleophilic aromatic substitution before additional nucleophilic amines are unmasked and the process iterated.

Identification of diamine linkers with differing reactivity and their application in the synthesis of melamine dendrimers

“…However, when using piperazine, dimerization of monochlorotriazines was observed under non-ideal reaction conditions that were usually attributed to concentration, rate of addition, ineffective stirring or lack thereof, temperature of addition and the magnitude of stoichiometric excess. 4,[8][9][10][11][12][13][14][15][16][17][18] Reactions with either p-aminobenzylamine or piperazine could be readily followed by NMR. The shift of the benzylic protons on reaction with the monochlorotriazine dendron or the desymmetrization of methylene groups of the piperazine group were diagnostic.…”

Synthesis and characterization of a triazine dendrimer that sequesters iron(III) using 12 desferrioxamine B groups

“…13 To functionalize these dendrimers, two different strategies have been pursued. The “functional monomer” approach relies on the incorporation of the drug of interest into a reactive dichlorotriazine.…”

Divergent synthesis of triazine dendrimers using a trimethylene-dipiperidine linker that increases efficiency, simplifies analysis, and improves product solubility

“…Initial success with monomer 2 relied on reacting the primary amines with dichlorotriazines. 14 The increased reactivity of dichlorotriazines (over the monochlorotriazines used here) overcomes the sluggish relative reactivity of the primary amine. Use of monomer 2 requires that the remaining chlorine atom be replaced prior to iteration.…”