The Scope and Future of Traceless Synthesis in Organic Chemistry

C.   W.   Phoon; M.   M.   Sim

doi:10.2174/1385272023373734

Abstract

Solid-phase organic synthesis has attracted considerable attention from the academic and industrial laboratories throughout the world in the last two decades. From peptides, to heterocycles, and then to the highly complex natural product combinatorial libraries, solid-phase organic synthesis has proven to be one of the most important fields in organic chemistry. One of the areas of exploding research is the use of traceless linkers to generate compounds which do not contain the undesired functional groups normally derived from the solid support. This review summarizes the solid-phase organic reactions published in the literatures and focuses primarily on those utilizing cleavage via traceless linkers or chemical reactions. The general routes to traceless cleavage include: [1] Electrophile- or Nucleophile-Induced Cleavage [2] Electrophile- or Nucleophile-Induced Cleavage with Modifications in Solution [3] Cyclorelease via Intramolecular Nucleophilic Attack [4] Metal-Mediated Cyclorelease [5] Activated Cleavage through Acylation [6] Cleavage via Cycloaddition or Cycloreversion [7] Reductive, Oxidative or Radical Cleavage [8] Photolytic Cleavage [9] Dissociation of Metal Complexes The review also describes our continual effort in the generation of cheaper and better traceless linkers, and combinatorial libraries with biological interest.

Keywords: Traceless Synthesis, Electrophile, Nucleophile-Induced Cleavage, benzimidazoles, dihydroisobenzofurans, pyrrolobenzodiazepines, quinoxalinones, fumiquinazoline derivatives, SULFONE-BASED LINKER, tetramethylguanidine