Mild Biamidine-Transfer Conditions for the Synthesis of Aliphatic Biguanides

Abstract

This study focuses on the development of new synthetic pathways to monosubstituted biguanides from amines. An exhaustive comparison of the conditions and reagents used for biamidine transfer was performed. New reagents were synthesized and optimized conditions for the synthesis of substituted biguanides under mild conditions were developed. Eventually, two high-yielding and straightforward protocols for the transfer of a biamidine group to various amines are proposed and their scope and limitations have been explored. These conditions include: i) a direct chromatography-free procedure and ii) an eco-friendly procedure in water compatible with bioinspired molecules. They are particularly efficient for the demanding conversion of aliphatic amines.

Diglycolamic Acid-Functionalized MWCNT-Augmented Polymeric Beads for Efficient Separation of Trivalent Lanthanides and Actinides

“…A previous report by Bardovskyi et al also indicated a similar trend of adsorption of Gd 3+ onto the diglycolamic acid-functionalized silica surfaces at various pH values. 31 Although the dissociation of diglycolamic acid is favorable at higher pH values, the observed decrease in the extraction of radionuclides at pH > 4 can be attributed to the hydrolysis of the radionuclides at higher pH values. Similar observations were observed by Gujar et al, 22 who reported a decrease in the uptake of Am 3+ and Eu 3+ by the GO-PES beads beyond pH 4.…”

Biguanide-Vancomycin Conjugates are Effective Broad-Spectrum Antibiotics against Actively Growing and Biofilm-Associated Gram-Positive and Gram-Negative ESKAPE Pathogens and Mycobacteria

“…Purification of 3a – e from the reaction mixture required silica-gel chromatography to remove unidentified side-products. Strategy 2 (Figure C), based on the work of Bardovskyi et al, involves a biguanide transfer reaction utilizing pyrazole-biguanides 9a – e to biguanidinylate amine 1 under mild-conditions which yields 3a – e upon precipitation from diethyl ether. Strategy 2 (Figure C) requires an additional synthetic operation to generate the activated intermediates 9a – e but removes a chromatographic purification and increases yields of 3a – e by 1.3- to 2.0- fold over strategy 1.…”

“…Pyrazole-biguanide 9a was synthesized in water following the published procedure, but further development was required to acquire functionalized pyrazole-biguanides 9b – e . N -alkylated pyrazole-biguanides 9b – d were synthesized from 8b – d with stoichiometric pyrazolium chloride in hot DMF.…”