Synthesis and properties of 1-(3′-dihydroxyboryl-2′,3′-dideoxyribosyl)pyrimidines

Abstract

Nucleoside analogues having a boronic acid in place of the 3-hydroxyl group of deoxyribose have been synthesized. The synthesis of 3'-dihydroxyboryl-2',3'-dideoxyribose was based on asymmetric homologation of boronic esters with (dihalomethyl)lithium, beginning from a (silyloxymethyl)boronic ester. A change of chiral director is required before introduction of the second stereocenter, and the direct displacement of (S,S)-1,2-dicyclohexyl-1,2-ethanediol by (1S,2S,3R,5S)-pinanediol was used for this purpose. Coupling of the pinanediol ester of the 1-acetoxy-3-dioxyboryl-5-tert-butylsilyloxy deoxyribose analogue with silylated pyrimidine bases was accomplished with trimethylsilyl bromide. The boronic acid nucleoside analogues were not cytotoxic toward Hep G2 (human hepatocarcinoma) cells. Decomposition occurred over a period of several hours at 37 °C, pH 7.4, with liberation of free pyrimidine base.

Synthesis of Sugar–Boronic Acid Derivatives: A Class of Potential Agents for Boron Neutron Capture Therapy

“…A careful literature survey was performed, revealing that such compounds are not described and very few examples of related structures are reported. 5 As the stability of boronic acids appears to be strongly dependent on the structural features of the whole molecule, the reported general information about their stability gives a broad overview. 6 A detailed review by Matteson systematically depicts the compatibility of boronic acids/esters in the presence of other functional groups.…”

“…Within a more general research program, we planned the synthesis of boronic acid derivatives of monosaccharides, where the boronic acid moiety substitutes one of the sugar’s hydroxyl groups. A careful literature survey was performed, revealing that such compounds are not described and very few examples of related structures are reported . As the stability of boronic acids appears to be strongly dependent on the structural features of the whole molecule, the reported general information about their stability gives a broad overview .…”

Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues

“…Cheng and co-workers reported an asymmetric synthesis of 2',3'-dideoxy-3'-boronic acid pyrimidine nucleosides [70]. The group used two highly diastereoselective reactions of chiral boronic esters with (dihalomethyl)lithium reagents to install the ultimate stereochemistry required at C3' and C4' (Scheme 15).…”

A Complementary Toolbox of Iterative Methods for the Stereo­selective Synthesis of Heteroatom-Rich Motives from C1-Building Blocks

“…This route was exploited by Cheng, Matteson, and co-workers for the synthesis of nucleoside analogues that contain a boronic acid moiety instead of the 3-hydroxy group of deoxyribose. 53 In this case only one more homologation/substitution sequence was necessary, to deliver the desired intermediate 55. Inversion of only one stereocenter without changing the chiral director was achieved after oxidative deprotection of the α-(3,4-dimethoxybenzyloxy)boronate 56.…”