Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

Abstract

A copper-mediated radiobromination of (hetero)aryl boronic pinacol esters is described. Cyclotron-produced [ 76/77 Br]bromide was isolated using an anion exchange cartridge, wherein the pre-equilibration and elution solutions played a critical role in downstream deboro-bromination. The bromination tolerates a broad range of functional groups, labeling molecules with ranging electronic and steric effects. Bologically active radiopharmaceuticals were synthesized, including two radiobrominated inhibitors of poly ADP ribose polymerase, a clinically relevant chemotherapeutic target for ovarian, breast, and prostate cancers.

Production and Processing of the Radionuclide 76Br

“…The 76 Br was distilled from the target at 1055 • C within 10 min and concentrated at a QMA Plus Light cartridge. Differing from published data [21,23], we used a chloride solution instead of an ammonia solution for the extraction of 76 Br. The attempts to extract 76 Br with ammonia solution were not successful.…”

“…Recent publications discuss 76 Br as a suitable radio tracer for theranostic radiopharamaceuticals [21][22][23].…”

Radiochemistry: A Hot Field with Opportunities for Cool Chemistry

“…Thus, efforts are underway to adapt these chemistries to the production of novel radiobrominated radiopharmaceuticals. 39 The bromide anion is significantly more nucleophilic than…”

“…40 Additionally, interest in radiobromine labeling chemistry has seen a resurgence, and several groups are working on adopting modern metal radiohalogenation methods for use with radiobromine (Scheme 1). 39,41,42 2.5. 211 At: Chemistry of Elements without Stable Isotopes.…”

“…While the development of labeling methodologies specific to radiobromine has not received the attention afforded to the other radiohalogens, bromine chemistry is generally versatile and well-understood. Thus, efforts are underway to adapt these chemistries to the production of novel radiobrominated radiopharmaceuticals . The bromide anion is significantly more nucleophilic than fluoride for use in nucleophilic substitution reactions, while, like iodine, it can be oxidized to form high molar activity electrophilic bromine sources .…”