Asymmetric synthesis of organoboron compounds bearing peptides and other nitrogen containing substituents (Immune deficiency).

摘要

Peptidyl boronic acids, alpha-amido boronic acid spiro chelates, and alpha-amido borinic acids were synthesized and their activities were tested against human immunodeficiency virus 1 (HIV-1) protease. In the synthesis of these compounds the C-terminus carboxy moiety of phenylalanine was replaced by hydroxyboron. Boron modification of these compounds increases their affinity toward enzymes. Peptidyl boronic acids are analogs of the phenylalanine terminal part of C-terminus scissile bond (Phe-Pro) of the HIV-1 encoded gag-pol polyprotein. Enzyme inhibitory profiles determined elsewhere showed that most of these compounds have both competitive and associative inhibitory activity against HIV-1 protease.; alpha-Amido boronic acid spiro chelates and alpha-amido borinic acids mimic amino acids on both sides of the scissile bond. alpha-Amido boronic acid spiro chelates proved less active toward HIV-1 protease than the corresponding peptidyl boronic acids, possibly because of their slow hydrolysis and unfolding. alpha-Amido borinic acids, a new class of boron compounds, have similar inhibitory activities with the corresponding boronic acids.; Moreover, reactions were carried out in which sterically hindered boronic esters of chiral diols were reacted with thionyl chloride and heterocyclic amines on borosilicate glass surface to form alkylhaloborane amine complexes and cyclic sulfite of the diols. In these reactions imidazole proved to be more efficient than pyridine and other heterocyclic amines. The product mixture of alkylhaloborane amine complexes contained compounds with one boron-bound chloride and two amine groups and other oligomeric species. Hydrolysis of alkylhaloborane amine complexes to boronic acids was carried out under mild, near neutral aqueous conditions. Under these conditions even sterically hindered boronic esters can be hydrolyzed, some of which cannot be hydrolyzed by other means.; Additionally, alkylazidoboronic esters were synthesized and their properties investigated. alpha-Azidoboronic esters were converted to the corresponding alpha-chloro (or alpha-bromo) beta-azido boronic esters, which were further subjected to several unsuccessful substitutions.