A-aminoboronates

Compound 51 was found to be unstable and difficult to purify, as described in the literature [93—95]. Therefore, 51 was not isolated, but was instead converted to the stable pinacol 1-acetamido-l-hexylboronate derivative 52. However, the acylated derivative 52 could not be purified by column chromatography as it was destroyed on silica gel and partially decomposed on alumina. Fortunately, we found that it dissolves in basic aqueous solution (pH > 11) and can then be extracted into diethyl ether when the pH of the aqueous layer is 5—6. Finally, pure 52 was obtained by repeated washing with weak acids and bases. It should be mentioned here that exposure to a strongly acidic solution, which also dissolves compound 51, results in its decomposition. Compared with other routes, the present two-step method involves mild reaction conditions (THF, ambient temperature) and a simple work-up procedure. It should prove very useful in providing an alternative access to a-aminoboronic esters, an important class of inhibitors of serine proteases. 

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... 

Scheme1.2 Application of the Matteson asymmetric homologation to the synthesis of chiral a-aminoboronic esters.

An optically pure y-silyloxyvinylboronate rearranged in the presence of thionyl chloride to afford the a-chloro-( )-crotylboronate with a high level of chirality transfer [122]. Important apphcations of this rearrangement are in the synthesis of polyke-tide natural products and a-aminoboronates [123,124). A few examples of transition metal catalyzed isomerizations of alkenylboronates have been reported, providing al-lylboronates in good yields [125,126). 

In general, the diboration of alkenes with [Pt(dba)2] required 50 while the use of [Pt(NBE)2] or [Pt(COD)2] (NBE = norbomene, COD = 1,5-cyclooctadiene) as precursors could diborate alkenes at room temperature." The reactions proceed smoothly to give 1,2-diborylaIkanes in high yield, and the catalysts were compatible with common functional groups. Further developments in the area by Baker showed that [Pt(COD)Cl2] could efficiently activate B2cat2 and promote the diboration of terminal alkenes, vinylarenes, alkynes, and aldimines (Scheme 9). The last example was a great advance because it represented the first direct approach toward a-aminoboronate esters. 

Mann G, John KD, Baker RT. Platinum catalyzed diboration using a commercially available catalyst diboration of aldimines to a-aminoboronate esters. Org Lett. 

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