A Facile High-Yield Synthesis of [10 B]-8-Dihydroxyboryl Harmine, a Potential Agent for Boron Neutron Capture Therapy

Abstract

The resurgence of interest in Boron Neutron Capture Therapy (BNCT) as a treatment for malignant lesions has resulted in the synthesis of numerous boron compounds as candidates for clinical use. BNCT is a selective radiotherapy using boron-10 which absorbs thermal neutrons and releases high Linear Energy Transfer (LET) alpha particles by 10 B (n, α) 7 Li reaction. The alpha radiation kills cells in the range of 5-9 µm from the site of the α generation. Therefore, it is theoretically possible to kill tumor cells without affecting adjacent healthy tissues, if 10 B-compounds could be selectively deliv- . They have a well know brain distribution, so these compounds, labeled with 10 B are potential agents for BNCT. A general synthetic method has been developed for the rapid and efficient production of boronated Harmine. Results And Discussion IodinationThe methods for iodination have been used previously for indolealkylamine [4] and phenethylamines [4] using thallium trifluoroacetate as specific oxidizing agent of molecular iodine for iodination of aromatic compounds [5]. BoronationWe used the condensation of the Grignard reagent from 8-I-Harmine with trimethylborate. This method was previously used [6] for preparation of phenol from phenylbromide and trimethylborate with formation of phenylboronic acid as intermediate and for preparation of boronic analogue of cho-