Here we describe a general method for the synthesis of 2,5-diaminoimidazoles, which involves a thermal reaction between α-aminoketones and substituted guanylhydrazines without the need for additives. As one of the few known ways to access the 2,5-diaminoimidazole motif, our method greatly expands the number of reported diaminoimidazoles and further supports our previous observations that these compounds spontaneously adopt the non-aromatic 4(H) tautomer. The reaction works successfully on both cyclic and acyclic amino ketone starting materials, as well as a range of substituted guanylhydrazines. Following optimization, the method was applied to the efficient synthesis of the advanced glycation end product (AGE) methylglyoxal-derived imidazolium crosslink (MODIC). We expect that this method will enable rapid access to a variety of biologically important 2,5-diaminoimidazole-containing products.
Keywords: advanced glycation end products; cyclization; diaminoimidazoles; sigmatropic rearrangement; total synthesis.
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.