Boronic esters, formation

Covalent polymers with reversible properties arising from dynamic covalent bonds such as disulfide exchange reaction [47 9], transesterification [50,51], transetherification [52], and boronate ester formation [53] were reported without respect to DCC. These studies should involve DCLs in... 

Rheault et al. [21] accessed a variety of heteroaryl linked benzimidazole (xii) derivatives following a convenient and mild microwave-assisted boronate ester formation. 

Rheault TR, Donaldson KH, Cheung M (2009) Convenient synthesis of heteroaryl-linked benzimidazoles via microwave-assisted boronate ester formation. Tetrahedron Lett 50 1399-1402... 

Other results involving liquid chromatography separations with imprinted metal oxides have been published in recent years. Norrlow et al. prepared surface imprinted silica gels functionalised with boronic acids that could form covalent linkages with riboses via boronate ester formation [43]. The gels were imprinted with templates containing two (nicotinamide adenine dinucleotide (NAD)) or four ribose units (bis-NAD 1, bis-NAD II). Columns were packed with the imprinted... 

Figure 7,14 The boronic ester formation can be used to prearrange appropriate building blocks. By ring closing metathesis, the non-macrocyclic precursor is turned into a bimacrocycle. When the norbornane template is removed (by ester hydrolysis or carbon-boron bond cleavage), er do-functionaHzed macrocycles are produced ...

Figure 3.1 Boronate ester formation. (Reprinted from Tetrahedron, 58, G. Springsteen, B. Wang, 5291. Copyright (2002), with permission from Elsevier.)...

Figure 3.7 Tetrahedral boronate ester formation. (Reprinted with permission from Journal of the American Chemical Society, 126, 52. Copyright (2004) American Chemical Society.)...

Boronic ester formation is an alternative process suitable for dynamic covalent chemistry. Nishimura and Kobayashi made use of the reversible condensation between an aryl-boronic acid and catechol in the development of dynamic hemicarcerand 42. Heating a 2 4 mixture of a tetra-boronic acid cavitand and biscatechol 43 resulted in the quantitative formation of 42. Again, the high efficiency is a result of the proper choice of the building blocks. Biscatechol 43, which in its lowest energy conformation is a perfect 120° ditopic bis-l,2-diol unit, is complementary to the orientation of the boronic acids in the cavitand building block to yield 42 with little or no strain. 

A fluorescein boronic acid derivative was prepared to function as the fluorescent partner and a series of methyl-red-inspired diols were synthesized as qnencher partners to probe the FOrster resonance energy transfer (FRET) quenching sensing regime based on boronate ester formation (Fignre 11). ... 

A detailed stndy of the combination of flnorescein boronic acid with diol-appended quenchers a-c and comparison with the fluorescence outputs of nonboron or nondiol-containing systems (i.e., fluorescein or methyl red were employed directly) revealed that the boronate ester formation results in enhanced quenching in each case, and that compound c is the best overall quencher. Nncle-osides were also shown to bind to the same fluorescein boronic acid derivative. While the quenching ability of each nucleoside tested was different, the same ratiometric quenching enhancement was observed in each case, sng-gesting similar binding affinities. 

Figure 9 Schematic depiction of a Peptide Borono-Lectin (PBL) binding to a glycan or glycoprotein via boronate ester formation. Inset to the right depicts the structure of the boronic acid-peptide linkage.

Scheme 2.1 Boronate ester formation reaction pathways studied by Pizer and Tihal.

The rules affecting modes of interaction between boron and nitrogen were further studied by Anslyn et al in 2009. They conducted analyses with the boronate ester formation of several o-aminomethylphenylboronic acids with different degrees of substitution around the nitrogen atom (Scheme 2.8). The experimental results showed that in polar protic solvents increasing the number of substituents on the amine group correlated with a slight increase in the ratio of N-B dative bond to solvent insertion in polar protic solvents. 

Scheme 2.8 Boronate ester formation from o-aminomethylphenylboronic acids.

The signal transduction in this system is thought to be derived from two separate, reversible complexations o-BBV /HPTS and o-BBV Vmonosac-charide. In the absence of sugar o-BBV and HPTS form a photo-inactive complex while in the presence of sugar o-BBV forms a boronate ester-complex. The boronate ester formation converts the dicationic viologen... 

Glucose Binding, Boronate Ester Formation and Complex Dissociation... 

Figurel.lO Specific examples of boronic ester formation with cyclic diols.

As discussed in the Introduction, boronic ester formation is a readily reversible process. Therefore, most of the inhibitors are used in their free acid form. However, if one uses a diol that can form a very tight covalent adduct with a boronic acid, one can make an ester inhibitor that is stable enough to hydrolysis on the time scale needed for the inhibitory activities. 

Figure 2. Transport Mediated by Transient Trigonal Boronate Ester Formation. Dopamine Transport...

Scheme 7 The equilibria for boronate ester formation couple to generate a thermodynamic cycle. The formation of the diol boronate anion complex is defined as Ktet and the formation of the diol boronic acid complex is defined as K,rig, where it is observed that > K ig. The acidity constant of the unbourid complex is defined as Ka and the acidity constant of the bound complex is defined as Kf, where it is observed that pKa > pKj.

Nishimura N, Kobayashi K (2008) Self-assembly of a cavitand-based capsule by dynamic boronic ester formation. Angew Chem Int Ed 47 6255-6258... 

Boronate ester formation precludes the involvement of the boron containing moiety serving as a hydrogen bond donor in hydrogen bonding interactions. 

FIGURE 5. Bis-diol functionalized porphyrins assemble into macrocycles based on boronate ester formation coupled with metal ligation to a Lewis basic pyridine. 

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