Large-scale green chemical synthesis of adjacent quaternary chiral centers by continuous flow photodecarbonylation of aqueous suspensions of nanocrystalline ketones.

To demonstrate the ease of scale-up and synthetic potential of some organic solid state reactions, we report the synthesis, crystallization, and solid state photochemistry of acyclic, homochiral, hexasubstituted (+)-(2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-pentanone 1. We demonstrate that solid state photodecarbonylation of (+)-(2R,4S)-1 affords (+)-(2R,3R)-2-carbomethoxy-3-cyano-2,3-diphenyl-butane 2 with two adjacent stereogenic, all-carbon substituted quaternary centers, in quantitative chemical yield and 100% diastereoselectivity and enantiomeric excess. The efficient multigram photodecarbonylation of (+)-(2R,4S)-1 as a nanocrystalline suspension in water using a continuous flow photoreactor shows that the large-scale synthesis of synthetically challenging compounds using photochemical synthesis in the solid state can be executed in a remarkably simple manner.

Sources of information and factual knowledge in Europeans with inflammatory bowel diseases: a cross-cultural comparison between German and Irish patients.

Background: Disease related knowledge may be associated with quality of life, coping skills and medication adherence. However, little is known of cross-cultural variations regarding inflammatory bowel disease knowledge or sources of information and no study has assessed knowledge in diverse European IBD populations.

Aim: To assess sources of information and patient knowledge in Irish and German inflammatory bowel disease patients.

Discovery of a stable molecular complex of an API with HCl: a long journey to a conventional salt.

We report formation and characterization of the first pharmaceutically acceptable and stable molecular complex of a mono-HCl salt of Compound 1 with HCl. The novelty of this discovery is due to the fact that there is only one major basic site in the molecule. Thus this complex is reminiscent of other noncovalent crystalline forms including solvates, hydrates, cocrystals and others.

Effective gelation of water by an amphiphilic drug.

We report the formation of aqueous gels at low concentrations (less than 1 wt%) of an amphiphilic drug, a derivative of a chromane-2-carboxylic acid, at pH values 6.2-6.4.

Development of a pharmaceutical cocrystal of a monophosphate salt with phosphoric acid.

We report the first case of a pharmaceutical cocrystal formed between an inorganic acid and an active pharmaceutical ingredient (API), which enabled us to develop a stable crystalline and bioavailable solid dosage form for pharmaceutical development where otherwise only unstable amorphous free form or salts could have been used.

Supramolecular behavior of the amphiphilic drug (2R)-2-ethylchromane-2-carboxylic acid arginine salt (a novel PPARalpha/gamma dual agonist).

Purpose: This study was conducted to evaluate the aggregation properties of an amphiphilic drug.

Methods: Aggregation of the drug was studied by various methods including phase-contrast and polarized microscopy, spectrophotometry, surface tensiometry, atomic force microscopy, and dynamic light scattering. Lymph-cannulated rats were used to assess fractions of drug that were absorbed into lymphatics.

Enantiospecific synthesis of vicinal stereogenic tertiary and quaternary centers by combination of configurationally-trapped radical pairs in crystalline solids.

[reaction: see text] Photochemical irradiation of crystalline (2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-butanone 1 led to highly efficient decarbonylation reactions. Experiments with optically pure and racemic crystals showed that the intermediate radical pairs undergo a highly diastereo- and enantiospecific radical-radical combination that leads to the formation of two adjacent stereogenic centers in good chemical yield and with high chemical control. Reactions with chiral crystals occurred with quantitative enantiomeric yields and >95% diastereomeric yields.