Aminoboronic acid

Peptide a-oxo acids, a-oxo esters, and a-oxoamides are also potent inhibitors of cysteine and serine proteases. Oxidation of peptide a-substituted carboxylic acid derivatives provides a general route to these compounds (Section 15.1.5). Peptide hydroxamic acids have been shown to be inhibitors of metalloproteinase and some have been reported to have antibiotic, anticarcinogenic, and antiviral activities. Peptide hydroxamic adds may be prepared by solution and solid-phase methods using a variety of resins (Section 15.1.6). a-Aminoboronic acids may be prepared by several routes and are reported to be inhibitors of aminopepti-dases. Procedures have been developed for their incorporation into peptides (Section 15.1.7). 

The effectiveness of a-aminoboronic acids with neutral side chains as inhibitors of proteases has prompted the preparation of inhibitors with functionalized side chains. These include those with a basic side chain (boroOrn, boroArg, and boroLys), sulfur-containing side chain (boroMet), a pyrrolidine (boroPro), and a 3-cyano-substituted benzyl side chain. The synthesis and properties of the neutral side-chain boronic acids are discussed first followed by descriptions of the preparation of more specialized a-aminoboronic acids. 

Table 1 lists various a-aminoboronic acids and peptides that have been synthesized. Within this section, a-aminoboronic acids are denoted from the relevant amino acid three-letter code preceded by boro, e.g. boroPhe is H2NCH(Bzl)B(OH)2. 

Scheme 1 a-Aminoboronic Acids by Reaction of Alkylboronic Acids15 61... 

Leueyl aminopeptidase Aminopeptidase I, Zinc, a-Aminoboronic acid... 

Hussain, M.A., et al. 1989. The use of alpha-aminoboronic acid derivatives to stabilize peptide drugs during their intranasal absorption. Pharm Res 6 186. 

Enzyme inhibitors can reduce the metabolic barrier to nasal delivery. The selection of an inhibitor is made on the basis of its ability to inhibit effectively the enzyme primarily responsible for the degradation of a particular compound. The coadministration of peptidase and protease inhibitors such as bacitracin, bestatin, amastatin, and aminoboronic acid derivatives has been found to promote the absorption of LHRH and growth hormone [42,43]. Aminopeptidase inhibitors in particular are effective in improving the bioavailability of enkephalins [44]. 

The functionalized boronic acids (15 and 16) are useful for sensing fluoride ion in aqueous solution. Electrochemical redox is used for the detection of fluoride ion with ferrocenyl-boronic acid (15) [8] and for fluorescence detection with aminoboronic acid (16) [9]. Molecule (16) can effectively detect concentration of fluoride ion in the range of 5-30 mM, where the fluoride adduct is stabilized by the additional hydrogen bonding with protonated amine at pH 5.5 as shown in structure 17 (Scheme 3.35). 

Dembitsky, V. M., Srebnik, M. Synthesis and biological activity of -aminoboronic acids, amine-carboxyboranes and their derivatives. Tetrahedron 2003, 59(5), 579-593. 

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