Pharmacologically active boranes

TL;DR: The first reported antibacterial activity of amine carboxyborane derivatives was reported in this article, where the B-phenyl group induced bacterial adhesion in all tested compounds, while its effect diminished when the boron atom was incorporated in a fused heterocyclic ring.

Abstract: Novel methods are described for the preparation of alkyldimethylamine cyano- boranes and β-hydroxylalkyldimethylamine cyanoboranes by C-lithiation of trimethylamine cyanoboranes followed by reaction with alkyl halides, aldehydes, and ketones. Lithiation of the monobromo derivatives of amine cyanoboranes led to the synthesis of the first examples of diborane derivatives of amine cyanoboranes. Bromo derivatives of amine cyanoboranes and amine carboxyboranes have been synthesized by new simple and efficient methods. Amine fluorocyanoboranes and amine fluorocarboxyboranes, new classes of compounds, have been prepared from the bromo precursors by fluorine/bromine exchange using fluori- nating reagents such as AgF and Et 3 N� 3HF. Eight different derivatives of oxazaborolidines were synthesized and evaluated for their affect on Streptococcus mutans viability, adhesion, and biofilm formation using 3 (H)-thymidine labeled bacteria, and fluorescent stained bacte- ria. This is the first reported antibacterial activity of this class of compounds. The minimal inhibitory concentration (MIC) values ranged from 0.26 to 10 mM. Structure-activity rela- tionship was observed. The B-butyl moiety of the oxazaborolidines contributed an anti-ad- hesion effect for all derivatives, while its effect diminished when the boron atom was incor- porated in a fused heterocyclic ring. The B-phenyl group induced bacterial adhesion in all tested compounds. In a separate study for boronated saccahrides and enzymatic inhibition, the complex formation between N-butylboronic acid and a series of monosaccharides was in- vestigated by 1 H, 13 C, and 11 B NMR spectroscopy and gas chromatography-mass spec- trometry (GC-MS). Then, a series of boronic acid compounds with protease inhibition prop- erties were prepared. The effect of added mono-, di-, and polysaccharides on the inhibitory activity of these compounds was studied. Potassium organotrifluoroborates were found to be reversible competitive inhibitors of α-chymotrypsin and trypsin. Based on 19 F NMR, it was speculated that they inactivate the enzymes as a result of the formation of hydrogen bonds between fluorine atoms of the inhibitors and the serine protease.