Solid‐Phase Synthesis of a Seventh‐Generation Inverse Poly(amidoamine) Dendrimer: Importance of the Loading Ratio on the Resin

Abstract

Here, this study overcomes the current barriers to efficient solid-phase synthesis of high-generation dendrimers by decreasing the loading ratio on the resin. G7 inverse poly(amidoamine) dendrimer is now prepared, for the first time, through a solid-phase synthesis using only 50% of the available reactive sites and by choosing a large resin. This preparation takes only 15 d to afford highly pure product in 80% yield with precipitation being the only purification procedure used. The results clearly show the amount of the initial monomer loaded on the resin to be a vital factor for the ability to use solid-phase synthesis to produce large dendrimers. This finding also sets stage for the applications of solid-phase synthesis for the preparation of other macromolecules.

Synthetic Methodologies for Chelating Polymer Ligands: Recent Advances and Future Development

“…[207] It should be noted the solid-phase synthesis of G7 inverse PAMAM dendrimer using only 50% of available reactive centers and by selecting a large resin. [208]…”

Solid-phase dendrimer synthesis: a promising approach to transform dendrimer construction

“…Careful consideration of all the issues mentioned above has enabled successful solid-phase synthesis of a variety of dendrimers up to generation 7 [43]. We will comment on all these issues using the specific examples presented below.…”

“…Thus, the corresponding 2nd-to 5th-generation dendrimers were delivered with yields of up to 93% within 1 week at a 0.10 mmol scale. Furthermore, by reducing the loading capacity of the solid support, it was possible to prepare a 7th-generation dendrimer via the same chemistry [43]; at full loading capacity, only defective dendrimers were obtained. Compared with conventional PAMAM dendrimers, these dendrimers have the amide bond linkage in the opposite direction (Fig.…”

Inverse Polyamidoamine (i‐PAMAM) Dendrimer Antimicrobials

“…Unfortunately, the blessing of this simple synthetic procedure is also its curse because the Michael addition is slowly reversible, such that PAMAM dendrimers can undergo retro‐ Michael reactions of the β‐alanine unit in their branches resulting in partial disassembly [13,14] . The labile β‐alanine unit was maintained in a PAMAM analog prepared on solid support by iterative Michael addition using ethyl acrylate and 1,3‐diaminopropane building blocks, [15] as well as in an inverse PAMAM obtained using solid‐phase peptide synthesis by iterative coupling of N,N ‐bis(N′‐Boc‐3‐aminopropyl)β‐alanine [16,17] …”