A multidetachable sulfamate linker successfully used in a solid-Phase strategy to generate libraries of sulfamate and phenol derivatives

The sulfamates and phenols constitute two families of compounds with numerous interesting biological properties. Using the ability of a new multidetachable sulfamate linker to generate these two families of compounds from the same resin, we designed and synthesized libraries of estradiol derivatives, sulfamoylated or not. A C-16β side chain was then judiciously diversified to target two key steroidogenic enzymes, the steroid sulfates and the type 1 17β-HSD. Four libraries of sulfamate and phenol derivatives were easily obtained by solid-phase parallel synthesis in good crude overall yields (13–62%) and HPLC purities (85–96%). Such strategy using the new two-in-line sulfamate linker could be also extended to other therapeutic targets than steroidogenic enzymes, thus adding to its potential.