Synthesis of a novel boronated 1‐aminocyclobutanecarboxylic acid as a potential boron neutron capture therapy agent

Abstract

A boronated aminocyclobutanecarboxylic acid was synthesized for potential use in neutron capture therapy. The synthesis involves the preparation of hydroxymethylcyclobutanone ketal, which is then converted to an amino acid using Bucherer-Strecker methodology. The molecule is modeled after the unnatural amino acid, 1-aminocyclobutanecarboxylic acid, which has demonstrated high uptake in brain tumors.

Evaluation of unnatural cyclic amino acids as boron delivery agents for treatment of melanomas and gliomas

“…Boronated analogues of unnatural cyclic amino acids (UNAA’s) belong to a new class of compounds that are gaining increasing attention as potentially more effective boron delivery agents for boron neutron capture therapy (BNCT) (Barth et al, 2012; Kabalka et al, 2001, 2011, 2004, 2003, 2006). The impetus for the design and synthesis of these compounds originated from the remarkable positron emission tomography (PET) observations in patients with the glioblastoma multiforme (GBM) and metastatic melanoma using fluorine-18 labeled boronophenylalanine (BPA) and carbon-11 labeled 1-aminocyclobutanecarboxylic acid.…”

Synthesis and characterization of nanosized polycarboranyl-porphyrazine conjugates

“…Several BNCT agents have been proposed so far, including boronated nucleosides [6,7], amino acids and peptides [8,9], phospholipids and liposomes [10][11][12][13], monoclonal antibodies, closomers [14,15], and dendrimers [16]. Due to their selectivity of accumulation in tumor over many normal tissues, porphyrins and phthalocyanines have also been proposed as boron carriers to target tumoral tissues in BNCT treatment, and indeed a number of papers reported the synthesis of carboranyl-porphyrins [17][18][19][20][21][22] and phthalocyanines [23,24] as model to develop novel radiosensitizers.…”

Carboranylporphyrazines for anti-cancer therapies: synthesis and physicochemical properties

“…In the past 15 years, several BNCT (Boron Neutron Capture Therapy) agents [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] have been proposed, including boronated nucleosides [5][6][7][8][9], amino acids and peptides [10,11], phospholipids [12], monoclonal antibodies, liposomes [13][14][15], closomers [16,17], and dendrimers [18,19]. Tetrapyrrolic macrocycles, a vast class of biologically relevant compounds often employed as sensitizers in anti-cancer photomedical treatments (including photodynamic therapy (PDT) [20][21][22][23][24] and photothermal therapy (PTT) [25][26][27][28]), have also been derivatized with boron-containing functions for possible use in BNCT [20,[29][30][31]…”