Recent development in the synthesis of unnatural boronated amino acids utilized for Cancer therapy.

Boron neutron capture therapy (BNCT) offers a highly selective approach to cancer treatment, its efficacy critically dependent on the design and delivery of boron-rich agents. Among the most promising candidates are unnatural boronated amino acids, which exploit endogenous amino acid transporters to achieve preferential tumor accumulation. This review surveys recent advances in the synthesis of carborane-bearing amino acid analogues, highlighting key strategies such as carborane cage alkylation, [2 + 2] cycloaddition with dichloroketene, Bucherer-Bergs hydantoin routes, and conjugate boronation with bis(pinacolato) diboron. Challenges related to stereoselectivity, diastereomer separation, and hydrolytic stability are critically discussed. Biological evaluation of these compounds in relevant tumor models demonstrates boron-delivery profiles that are competitive with and in the selected cases superior to the established clinical standard, L-p‑boronophenylalanine (BPA). Collectively, the progress outlined here reflects a maturing field with tangible prospects for broadening the clinical utility of BNCT.