Stability of Boronic Esters to Hydrolysis: A Comparative Study

Abstract

Boronic esters are key intermediates in the synthesis of biologically active compounds such as thrombin and proteasome inhibitors. However, they have low hydrolytic stability both during synthetic reactions and in biological media. We report the preparation of several boronic esters and a comparative study of their stability to hydrolysis vs. the corresponding pinanediol boronic esters, which are among the most hydrolytically stable. We discovered that the boronic esters derived from (1,1′-bicyclohexyl)-1,1′-diol are the most stable among those examined.

Reversible Linkage of Two Distinct Small Molecule Inhibitors of Myc Generates a Dimeric Inhibitor with Improved Potency That Is Active in Myc Over-Expressing Cancer Cell Lines

“…Importantly, the dimerization constant can be adjusted via substituents. For example, the introduction of steric effects on either linker component disfavors boronate ester hydrolysis, shifting the monomer-dimer equilibrium towards dimer formation, which results in improved dimerization constants [ 7 , 8 ] and can translate into improved potencies of the resulting dimeric inhibitor. Both boronic acid and diol linkers can be appended to desired ligands through a wide range of connector moieties using facile synthetic methods.…”

Reaction‐Based and Single Fluorescent Emitter Decorated Ratiometric Nanoprobe to Detect Hydrogen Peroxide

“…To achieve a drastic change in polarity on treatment with H 2 O 2 , short‐chained alkylboronic esters with sterically bulky masking groups were chosen as the reactive moiety. In addition, the highly sterically hindered boronic esters have sufficient hydrolytic stability that they will not be hydrolyzed during the polymerization and the resulting HP‐3 HF polymers would possess long‐term stability in aqueous media (see Figure S3 in the Supporting Information) 18. As a negative control, the H 2 O 2 ‐insensitive cross‐linked polymeric nanoparticle HPin‐3 HF , in which DCBE was replaced by the H 2 O 2 ‐insensitive monomer CyAM , was also fabricated (see Scheme S2 in the Supporting Information for the detailed structure).…”

“…In addition, the highly sterically hindered boronic esters have sufficient hydrolytic stability that they will not be hydrolyzed during the polymerization and the resulting HP-3 HF polymers would possess long-term stability in aqueous media (see Figure S3 in the Supporting Information). [18] As a negative control, the H 2 O 2 -insensitive cross- linked polymeric nanoparticle HPin-3 HF, in which DCBE was replaced by the H 2 O 2 -insensitive monomer CyAM, was also fabricated (see Scheme S2 in the Supporting Information for the detailed structure). Detailed synthetic procedures and structural characterization of the monomers are given in the Experimental Section and Supporting Information, respectively.…”

Donor‐Acceptor Substituted 2‐Phenylpyridines by Means of Reductive C,C–Cross Coupling Reaction

“…The most functional groups in C,C ‐cross‐coupling reactions are tolerated in the Suzuki type reactions. Nevertheless, some draw‐backs of this type of cross‐coupling reactions are, for example, the requirement of a boronic acid or anhydride, mostly prepared from the corresponding halide, and, in some cases, the sensitivity of the boronic unit to electron donors like hydroxy groups or carboxylic acids. Those functionalities commonly require a protection even in Suzuki‐type of C,C‐cross‐coupling reactions.…”