One-Pot, Multi-Component Green Microwave-Assisted Synthesis of Bridgehead Bicyclo[4.4.0]boron Heterocycles and DNA Affinity Studies

Abstract

Anthranilic acids, salicylaldehydes and arylboronic acids reacted in EtOH/H2O (1/3) at 150 °C under microwave irradiation for 1 h to give, in excellent yields and purity, twenty-three bridgehead bicyclo[4.4.0]boron heterocycles via one-pot, three-component green synthesis. The scope and the limitations of the reactions are discussed in terms of the substitution of ten different anthranilic acids, three salicylaldehydes and three arylboronic acids. The replacement of salicylaldehyde with o-hydroxyacetophenone demanded a lipophilic solvent for the reaction to occur. Eight novel derivatives were isolated following crystallization in a toluene-containing mixture that included molecular sieves. The above one-pot, three-component reactions were completed under microwave irradiation at 180 °C within 1.5 h, thus avoiding the conventional prolonged heating reaction times and the use of a Dean–Stark apparatus. All derivatives were studied for their affinity to calf thymus DNA using proper techniques like viscosity and UV–vis spectroscopy, where DNA-binding constants were found in the range 2.83 × 104–8.41 × 106 M−1. Ethidium bromide replacement studies using fluorescence spectroscopy indicated Stern–Volmer constants between 1.49 × 104 and 5.36 × 104 M−1, whereas the corresponding quenching constants were calculated to be between 6.46 × 1011 and 2.33 × 1012 M−1 s−1. All the above initial experiments show that these compounds may have possible medical applications for DNA-related diseases.