Solid phase synthesis of oligomeric guanidiniums

Article abstract of DOI:10.1016/S0040-4020(98)00900-4

Oligomers containing guanidinium linkages prepared via solid phase organic synthesis are of interest as possible therapeutic agents and in the assembly of supramolecular architectures. Efficient routes to these oligomers must be developed before their potential may be fully realized. Herein, four routes for their stepwise solid phase synthesis are described. In the first, a resin-bound thiourea was converted to a guanidinium using 2-chloro-1- methylpyridinium iodide. The second method utilized aza-Wittig couplings to prepare guanidiniums from resin-bound carbodiimides. Next, highly activated monomers prepared from bis-tert-butyloxycarbonythioureas and 2,4- dinitrofluorobenzene formed guanidiniums upon reaction with terminal amines. The optimum route, however, relied upon the 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride promoted coupling of a protected thiourea monomer with a resin-bound amine to produce the guanidinium linkage. The thiourea monomers for this method are easily prepared from mono-protected diamines and benzoyl- or Fmoc-isothiocyanate. The procedure is straightforward, proceeds cleanly in a relatively short period of time, and is compatible with several functional groups.