Synthesis of isotopically labelled [3‐¹⁴C]‐ and [3,3‐²H₂]‐5‐fluoro‐1,3‐dihydro‐1‐hydroxy‐2,1‐benzoxaborole (AN2690), a new antifungal agent for the potential treatment of onychomycosis

Abstract

Abstract5‐Fluoro‐1,3‐dihydro‐1‐hydroxy‐2,1‐benzoxaborole (AN2690) is a new antifungal agent for the potential treatment of onychomycosis. During the preclinical development phase, it was necessary to synthesize the radioisotope [3‐14C]‐5‐fluoro‐1,3‐dihydro‐1‐hydroxy‐2,1‐benzoxaborole and the deuterium isotope [3,3‐2H2]‐5‐fluoro‐1,3‐dihydro‐1‐hydroxy‐2,1‐benzoxaborole for in vitro studies. We report the synthesis of these two isotopically labelled derivatives. Copyright © 2007 John Wiley & Sons, Ltd.

Benzoxaboroles – Old compounds with new applications

“…After the discovery of its antifungal properties [10,11,59], systematic investigations of biological activity of substituted benzoxaboroles were carried out [12,60]. Some general rules concerning their activity against onychomycosis were determined:…”

Influence of the Substituents on the Structure and Properties of Benzoxaboroles

“…10,11 After the discovery of its antifungal properties, [12][13][14] systematic investigations of biological activity of substituted benzoxaboroles were carried out. 15,16 Recently, 5-chlorosubstituted benzoxaborole, AN2718, is being developed for topical treatment of tinea pedis. 15 Benzoxaborole with cyanophenoxy substituents in five-position reveals anti-inflammatory activity against psoriasis, a common skin disease characterized by chronic inflammation.…”

“…Only recently has great attention been paid to a new application of these compounds in medicine. 5-Fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, AN2690, is a broad-spectrum antifungal drug that easily transits through the nail plate. , After the discovery of its antifungal properties, – systematic investigations of biological activity of substituted benzoxaboroles were carried out. , Recently, 5-chloro-substituted benzoxaborole, AN2718, is being developed for topical treatment of tinea pedis . Benzoxaborole with cyanophenoxy substituents in five-position reveals anti-inflammatory activity against psoriasis, a common skin disease characterized by chronic inflammation.…”

Recent developments in carbonylation chemistry using [13C]CO, [11C]CO, and [14C]CO

“…During the design of new synthetic routes toward carbon‐14 labeled pharmaceuticals, carbonylation chemistry with [ 14 C ]CO holds a key position. Installation of carbon‐14 by means other than carbonylation is available, including the classical examples of carboxylation with [ 14 C ]CO 2 or cyanation via nucleophilic [ 14 C ]cyanide . However, carboxylation often involves activation of the starting materials by halide to lithium exchange or though the generation of Grignard reagents, approaches that compromise the functional group compatibility of the synthetic intermediate.…”