Charge Transfer Complexes (CTCs) with Pyridinium Salts: Toward Efficient Dual Photochemical/Thermal Initiators and 3D Printing Applications.

In both organic and polymer synthesis, photochemistry of charge transfer complexes (CTCs) is considered as a powerful approach to expand visible-light-driven radical chemistry reaction. One reports herein on the development of a class of useful CTCs using pyridinium salts as efficient electron acceptors (combined with N, N, 3,5-tetramethylaniline, TMA) to achieve a multiwavelength (375-560 nm) metal-free LED photopolymerization process under mild conditions (open to air, without monomer purification and inhibitor removal). The UV-vis absorption spectra and molecular modeling simultaneously verify its potential blue-green absorbing wavelength range. Also, their good thermal initiation behavior at relatively low temperatures makes it easier to achieve thick samples and/or polymerization in the shadow region in practice. More importantly, with excellent photoinitiating capability, the formulation is successfully applied to direct laser write (DLW) and high-resolution 3D printing, yielding a series of objects with well-defined structures, such as letters, ring, solid squares, and chess pieces. These new pyridinium salt acceptors further extend the applicability to visible photopolymerizable resins and additive-containing formulations for efficient surface and deep curing.

Glucose-based spiro-isoxazolines: a new family of potent glycogen phosphorylase inhibitors.

A series of glucopyranosylidene-spiro-isoxazolines was prepared through regio- and stereoselective [3+2]-cycloaddition between the methylene acetylated exo-glucal and aromatic nitrile oxides. The deprotected cycloadducts were evaluated as inhibitors of muscle glycogen phosphorylase b. The carbohydrate-based family of five inhibitors displays K(i) values ranging from 0.63 to 92.5 microM. The X-ray structures of the enzyme-ligand complexes show that the inhibitors bind preferentially at the catalytic site of the enzyme retaining the less active T-state conformation. Docking calculations with GLIDE in extra-precision (XP) mode yielded excellent agreement with experiment, as judged by comparison of the predicted binding modes of the five ligands with the crystallographic conformations and the good correlation between the docking scores and the experimental free binding energies. Use of docking constraints on the well-defined positions of the glucopyranose moiety in the catalytic site and redocking of GLIDE-XP poses using electrostatic potential fit-determined ligand partial charges in quantum polarized ligand docking (QPLD) produced the best results in this regard.

Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase.

Glucopyranosylidene-spiro-1,4,2-oxathiazoles were prepared in high yields by NBS-mediated spiro-cyclization of the corresponding glucosyl-hydroximothioates. In an effort to synthesize analogous glucopyranosylidene-spiro-1,2,4-oxadiazolines, with a nitrogen atom instead of the sulphur, attempted cyclizations resulted in aromatization of the heterocycle with opening of the pyranosyl ring. Enzymatic measurements showed that some of the glucose-based inhibitors were active in the micromolar range. The 2-naphthyl-substituted 1,4,2-oxathiazole displayed the best inhibition against RMGPb (K(i)=160 nM), among glucose-based inhibitors known to date.

Synthesis and structure-activity relationships of C-glycosylated oxadiazoles as inhibitors of glycogen phosphorylase.

A series of per-O-benzoylated 5-beta-D-glucopyranosyl-2-substituted-1,3,4-oxadiazoles was prepared by acylation of the corresponding 5-(beta-D-glucopyranosyl)tetrazole. As an alternative, oxidation of 2,6-anhydro-aldose benzoylhydrazones by iodobenzene I,I-diacetate afforded the same oxadiazoles. 1,3-Dipolar cycloaddition of nitrile oxides to per-O-benzoylated beta-D-glucopyranosyl cyanide gave the corresponding 5-beta-D-glucopyranosyl-3-substituted-1,2,4-oxadiazoles. The O-benzoyl protecting groups were removed by base-catalyzed transesterification. The 1,3,4-oxadiazoles were practically inefficient as inhibitors of rabbit muscle glycogen phosphorylase b while the 1,2,4-oxadiazoles displayed inhibitory activities in the micromolar range. The best inhibitors were the 5-beta-D-glucopyranosyl-3-(4-methylphenyl- and -2-naphthyl)-1,2,4-oxadiazoles (K(i)=8.8 and 11.6 microM, respectively). A detailed analysis of the structure-activity relationships is presented.

Synthesis and evaluation of sulfamide-type indolizidines as glycosidase inhibitors.

A practical synthesis of reducing sulfamide-derived iminosugar glycomimetics related to the indolizidine glycosidase inhibitor family is reported. The polyhydroxylated bicyclic system was built from readily accessible hexofuranose derivatives through a synthetic scheme that involves 5,6-cyclic sulfamides. Further intramolecular nucleophilic addition of the sulfamide nitrogen atom to the masked aldehyde group of the monosaccharide in the open chain form afforded the target sugar mimics. By starting from d-glucose and d-mannose precursors, 2-aza-3,3-dioxo-3-thiaindolizidine derivatives with hydroxylation profiles that matched those of (+)-castanospermine and 6-epi-(+)-castanospermine were obtained. In vitro screening against a panel of glycosidases evidenced a high selectivity towards alpha-mannosidase.