Synthesis of Gelatin Methacryloyl Analogs and Their Use in the Fabrication of pH-Responsive Microspheres.

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering.

Diindolylamine Preparation and Stability Investigations.

The synthesis of diindolylamines via the palladium-catalyzed cross-coupling of aminoindoles and bromoindoles has been investigated, and efficient coupling conditions using BrettPhos, Pd(OAc), KCO, and tBuOH have been identified. The diindolylamines were found to be unstable in ambient conditions. Blocking the reactive 3-position of the bromoindole coupling partner with a -butyl group results in a diindolylamine with improved air stability.

Diastereomerically Differentiated Excited State Behavior in Ruthenium(II) Hexafluoroacetylacetonate Complexes of Diphenyl Thioindigo Diimine.

Mono- and diruthenium hexafluoroacetylacetonate (hfac) complexes of the thioindigo-N,N'-diphenyldiimine chelating ligand 3 have been prepared. The thioindigo diimine ligand binds to ruthenium in a bidentate fashion in the mononuclear compound 2 and serves as a bidentate chelating bridging ligand in the diruthenium complexes 1a and 1b. Compound 2 was isolated as a racemic mixture while the diruthenium complexes were isolated as the meso (ΔΛ) 1a and rac (ΔΔ and ΛΛ) 1b diastereomers.

Direct N-acetyl enamine formation: lithium bromide mediated addition of methyllithium to nitriles.

An improved protocol for N-acetyl enamine formation is disclosed which involves LiBr-mediated addition of MeLi to substituted nitriles. The resulting enamides are isolated in high yields and excellent purity which permits subsequent hydrogenation at very low catalyst loading.

Synthesis of a tetrahydropyran NK1 receptor antagonist via asymmetric conjugate addition.

Two asymmetric syntheses of the NK(1) receptor antagonist 1-[2-(R)-{1-(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(R)-(3,4-difluorophenyl)-4-(R)-tetrahydro-2H-pyran-4-ylmethyl]-3-(R)-methylpiperidine-3-carboxylic acid (1) were developed. In both routes, the core tetrahydropyran stereochemistry was established by asymmetric conjugate addition to an alpha,beta-unsaturated ester (6), using an amide of the chiral auxiliary pseudoephedrine. Selective ester reduction then allowed formation of lactone 2 with the thermodynamically preferred trans geometry.

Michael reactions of pseudoephedrine amide enolates: effect of LiCl on syn/anti selectivity.

The stereochemical outcome of the asymmetric Michael reaction of pseudoephedrine amide enolates changes dramatically in the presence of LiCl. Reaction of the enolate in the absence of LiCl results in formation of the anti Michael adduct with high selectivity, whereas in the presence of lithium chloride the syn adduct is favored. This method provides access to enantiomerically enriched trans-3,4-disubstituted delta-lactones from the anti Michael adducts by a two step reduction/lactonization sequence.

Pseudoephedrine as a chiral auxiliary for asymmetric Michael reactions: synthesis of 3-aryl-delta-lactones.

[reaction: see text] The asymmetric Michael reaction of pseudoephedrine amides is reported. The 1,5-dicarbonyl products are converted to 3-aryl-delta-lactones in a two-step reduction/lactonization sequence. This method provides access to enantiomerically enriched trans-3,4-disubstituted delta-lactones.