Synthesis of a series of boronated unnatural cyclic amino acids as potential boron neutron capture therapy agents

摘要

New boronated unnatural cyclic amino acids, 1 -6, were synthesized for potential use in neutron capture therapy. In order to understand the effect of molecular lipophilicity on the biological activity, different linkers were introduced between the boronic acid and 1-aminocycloalkanecarboxylic acid moieties. The key step in the syntheses was the preparation of a series of alkenyl-substituted cycloalkanones, which were subsequently converted to amino acids via the Biicherer-Strecker reaction. The introduction of the boronic acid function into hydrantoins 19 - 24 was realized by hydroboration reactions using diisopinocampheylborane (lpc2BH). The target boronated amino acids were modeled after 1 -aminocyclobutanecarboxylic acid and 1 -amino-3-boronocyclopentanecarboxylic acid, which have previously demonstrated high uptake in tumors.