6301-87-7Relevant articles and documents
Synthesis and conversion of primary and secondary 2-aminoestradiols into A-ring-integrated benzoxazolone hybrids and theirin vitroanticancer activity
Kovács, Ferenc,Gopisetty, Mohana K.,Adamecz, Dóra I.,Kiricsi, Mónika,Enyedy, éva A.,Frank, éva
, p. 13885 - 13896 (2021/04/22)
Hybrid systems are often endowed with completely different and improved properties compared to their parent compounds. In order to extend the chemical space toward sterane-based molecular hybrids, a number of estradiol-derived benzoxazol-2-ones with combined aromatic rings were synthesizedviathe corresponding 2-aminophenol intermediates. 2-Aminoestradiol was first prepared from estrone by a two-step nitration/reduction sequence under mild reaction conditions. Subsequent reductive aminations with different arylaldehydes furnished secondary 2-aminoestradiol derivatives in good yields. The proton dissociation processes of the aminoestradiols were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pK1and pK2values are attributed to the+NH3or+NH2R and OH moieties, and both varied by the different R substituents of the amino group. Primary and secondary 2-aminoestradiols were next reacted with carbonyldiimidazole as a phosgene equivalent to introduce a carbonyl group with simultaneous ring-closure to give A-ring-fused oxazolone derivatives in high yields. The novel aminoestradiols and benzoxazolones were subjected toin vitrocytotoxicity analysis and were found to exert cancer cell specific activity.
