Investigating the Solubility and Activity of a Novel Class of Ice Recrystallization Inhibitors

O-aryl-β-D-glucosides and N-alkyl-D-gluconamides are two classes of effective ice recrystallization inhibitors (IRIs), however their solubilities limit their use in cryopreservation applications. Herein, we have synthesized and assessed phosphonate analogues of small-molecule IRIs as a method to improve their chemical and physical properties. Four sodium phosphonate compounds 4–7 were synthesized and exhibited high solubilities greater than 200 mM. Their IRI activity was evaluated using the splat cooling assay and only the sodium phosphonate derivatives of α-methyl-D-glucoside (5-Na) and N-octyl-D-gluconamide (7-Na) exhibited an IC50 value less than 30 mM. It was found that the addition of a polar sodium phosphonate group to the alkyl gluconamide (1) and aryl glucoside (2) structure decreased its IRI activity, indicating the importance of a delicate hydrophobic/hydrophilic balance within these compounds. The evaluation of various cation-phosphonate pairs was studied and revealed the IRI activity of ammonium and its ability to modulate the IRI activity of its paired anion. A preliminary cytotoxicity study was also performed in a HepG2 cell line and phosphonate analogues were found to have relatively low cytotoxicity. As such, we present phosphonate small-molecule carbohydrates as a biocompatible novel class of IRIs with high solubilities and moderate-to-high IRI activities.

Synthesis of Phosphonomethylated Bromoacetylfurans and Their Reactions with 1,3-Dicarbonyl Compounds

Bromination of (diethoxyphosphorylmethyl)acetylfurans with dioxane dibromide in the mixture of chloroform and acetic acid in presence of traces of hydrogen bromide at room temperature proceeds selectively at the methyl group of ketone does not involving phosphonate group. Obtained bromoacetyl derivatives were used for alkylation of acetoacetic ester and cyclohexan-1,3-dione. Reaction of 1,4-diketone prepared from acetoacetic ester with hydrazine hydrate in ethanol at room temperature leads to formation of furylpyrazines due to aromatization of intermediate azines by means of air oxygen.

[3+2] Cycloaddition of N-Aminopyridines and Perfluoroalkynylphosphonates: Facile Synthesis of Perfluoroalkylated Pyrazolo[1,5-a]pyridines Containing a Phosphonate Moiety

1,3-Zwitterions generated from N-aminopyridines in the presence of base are trapped by perfluoroalkynylphosphonates to yield a variety of perfluoroalkylated pyrazolo[1,5-a]pyridine derivatives bearing a phosphonate group. The salient features of these [3+2] cycloadditions include operational simplicity, good tolerance of functional groups, and good to excellent yields at room temperature.

Dimethyl (7-hydroxy-4-methyl-2-oxo-2H-chromen-3-yl)phosphonate

In the title compound, C12H13O6P, the coumarin ring system is essentially planar [dihedral angle between the rings = 1.32 (16)°] and the methoxy groups and double-bonded O atom of the phosphonate group are disordered over two sets of sites [occupancy ratio 0.537 (2):0.463 (2)]. In the crystal, C—H...O hydrogen bonds involving the disordered phosphonate O atom as acceptor occur, which generate [100] chains. Weak C—H...O and aromatic π–π stacking interactions [minimum centroid–centroid separation = 3.713 (2) Å] are also observed.

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry. As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic compounds bearing a phosphonate group on the ring is given.