SOLID-PHASE SYNTHESIS OF OLIGOMERIC GUANIDINIUMS

Oligomers containing guanidinium linkages prepared via solid phase org anic synthesis are of interest as possible therapeutic agents and in t he assembly of supramolecular architectures. Efficient routes to these oligomers must be developed before their potential may be fully reali zed. Herein, four routes for their stepwise solid phase synthesis are described. In the first, a resin-bound thiourea was converted to a gua nidinium using 2-chloro-1-methylpyridinium iodide. The second method u tilized aza-Wittig couplings to prepare guanidiniums from resin-bound carbodiimides. Next, highly activated monomers prepared from bis-tert- butyloxycarbonythioureas and 2,4-dinitrofluorobenzene formed guanidini ums upon reaction with terminal amines. The optimum route, however, re lied upon the 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochlor ide promoted coupling of a protected thiourea monomer with a resin-bou nd amine to produce the guanidinium linkage. The thiourea monomers for this method are easily prepared from mono-protected diamines and benz oyl- or Fmoc-isothiocyanate. The procedure is straightforward, proceed s cleanly in a relatively short period of time, and is compatible with several functional groups. (C) 1998 Elsevier Science Ltd. All rights reserved.