Design, development, synthesis, and crystal structure of the prototype of a new class of deep blue-fluorescing boron heterocycle estrogen mimics

Abstract

To further the development of boron heterocyclic compounds that are useful to medicinal chemistry, we demonstrate how the class of compounds known as the diazaborines can be elaborated to produce an exceptionally close structural mimic of a natural estrogen. After building progressively closer models, a benzyloxy-substituted formylphenylboronic acid was ultimately condensed with a hydroxymethylated β-hydrazinocyclopentenone to give, after debenzylation, an isosteric mimic (diazaborine 1) of the naturally-occurring estrogen equilenin and the prototype of a new class of boron heterocycle estrogen mimics. X-ray crystallography revealed the prototype to be planar, with a transmolecular interoxygen distance virtually identical to that found in equilenin and with a strong hydrogen-bond-donating hydroxyl group. From this it can be anticipated that members of this unique class of boron heterocycle estrogen mimics will be found to possess useful biological properties. Furthermore, the prototype was found to fluoresce in the deep blue region of the visible spectrum, and so the development of members serving as light-emitting probes in biochemical and biological studies can also be anticipated.