Chapter 8 α-Aminoboronic acids, amine cyanoboranes, amine carboxyboranes and their derivatives

Abstract

This chapter describes developments in the synthesis and biological activity of α-aminoboronic acids, amine cyanoboranes, amine carboxyboranes and their derivatives as potential therapeutic agents. α -Amino acid analogues are of considerable interest as inhibitors of enzymes involved in amino acid and peptide metabolism. In particular, α -amino alkylboronic acids, in which the carboxyl group of amino acids is replaced by boronic acid function, constitute a unique class of amino acid mimics from which a number of potent enzyme inhibitors have been synthesized. The inhibitory activity mainly stems from the fact that the tetrahedral adduct of electrophilic boronic acid is a good mimic of the putative tetrahedral transition state or intermediate encountered in the enzymatic hydrolysis or formation of peptides. Because, the peptide hydrolysis and formation invariably involves the tetrahedral high energy species in the course of the reaction, these amino acid mimics serve as a general key element for inhibitors of a broad spectrum of proteases and peptide ligases. Serine protease inhibitors provide promising compounds having a boronic acid chelating moiety and a high-inhibitory activity. Amine cyanoboranes, amine carboxyboranes, and amine carboxyborane amides and esters are intriguing groups of compounds. They can be regarded as isoelectronic and isostructural boron analogues of amino acids, neurotransmitters, nucleosides, nucleic acids, and boronated DNA and RNA. Such compounds have potent antitumor, anti-inflammatory, hypolipidemic, anti-ostoeoporotic, antineoplastic, and other promising biological activities.