78902-01-9Relevant academic research and scientific papers
Probing the specificity of the serine proteases subtilisin Carlsberg and α-chymotrypsin with enantiomeric 1-acetamido boronic acids. An unexpected reversal of the normal L -stereoselectivity preference
Martichonok, Valeri,Jones, J. Bryan
, p. 950 - 958 (2007/10/03)
Enantiomeric 1-acetamido boronic acids, which are N-acetyl transition state analog inhibitor analogs of L-and D-forms of the amino acids alanine, phenylalanine, p-fluorophenylalanine, p-chlorophenylalanine, and 1-naphthylalanine, have been evaluated as inhibitors of the serine proteases subtilisin Carlsberg (SC) and α-chymotrypsin (CT). All of the boronic acids are powerful competitive inhibitors of both enzymes, with, as expected, the L-enantiomers being generally more potent than the D-enantiomers. However, a dramatic reversal of the normal stereoselectivity preference was observed in the inhibition of CT by [1-acetamido-2-(1-naphthyl)ethyl]boronic acid, with the D-enantiomer becoming a 25-fold more potent inhibitor than the L-enantiomer. Furthermore, the K1 of 127 nM for CT inhibition by this D-enantiomer is the lowest of any of the boronic acids evaluated. Molecular modeling analyses of the possible binding modes of the inhibitors suggest that the stereoselectivity reversal is due to S1-pocket orientations of naphthyl groups that are different from those of the aromatic side chains of the phenylalanine analogs.
Synthesis of 1-amino-2-phenylethane-1-boronic acid derivatives
Matteson, Donald S.,Sadhu, Kizhakethil Mathew
, p. 614 - 618 (2008/10/08)
The boron analogue of N-acetylphenylalanine, (R)-1-acetamido-2-phenylethane-1-boronic acid (5b), has been synthesized from (+)-pinanediol phenylmethane-1-boronate (1b), which was converted by (dichloromethyl)lithium to the (S)-1-chloro-2-phenylethane-1-boronate (2b), then with N-lithiohexamethyldisilazane to the silylated 1-amino-2-phenylethane-1-boronic ester 3b, which was desilylated and acetylated in situ to (+)-pinanediol (R)-1-acetamido-2-phenylethane-1-boronate (4b) and then cleaved to the free boronic acid 5b with boron trichloride. 1-Amino-2-phenylethane-1-boronic esters (6) were found to be isolable but unstable, deboronating to 2-phenylethylamine under the influence of heat or hydroxylic solvents. 1-Amino-2-phenylethane-1-boronic acid, though not isolable, partially survives for an hour in cold aqueous solution. Attempts to synthesize the stable α-acetamido boronic esters (4) directly by reaction of lithioacetamide with 1-halo-2-phenylethane-1-boronic esters (2) have resulted in a major proportion of O-alkylation to form imino esters. Pinacol 1-acetamidino-2-phenylethane-1-boronate (8) has been obtained from the α-iodo boronic ester 2d and acetamidine.
