Supports for Solid-Phase Organic Synthesis

Dendronized Solid-phase Supports for Organic Synthesis 

This dual linker approach allowed selective cleavage of the peptide from the dendrimer using 1% TFA/CH2CI2 without cleaving the dendrimer from the resin. Proceeding from the TentaGel resin the final product was obtained in 44% yield 

PS-PEG-PAMAM[G3.0] dendronized support with HMPB-linker 

A number of different reaction conditions were investigated for the Mitsunobu reaction and DIAD/PPh3 proved to be the most efficient combination of reagents. The dendronized support was then compared with the conventional TentaCel resin keeping the scaffold on the resin constant (glycine and 4-hydroxyphenylacetic acid) and employing four different alcohols. Much better yields were obtained 

Following this synthetic route two known active compounds of this substance class (Ro44-9883 and TAK-029) were synthesized. The overall isolated yields were comparable with those obtained in solution but this route did not require isolation and purification of the intermediates. 

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