A multi-gram-scale stereoselective synthesis of Z-endoxifen.

Z-Endoxifen is widely regarded as the most active metabolite of tamoxifen, and has recently demonstrated a 26.3% clinical benefit in a phase I clinical trial to treat metastatic breast cancer after the failure of standard endocrine therapy. Future pharmacological and pre-clinical studies of Z-endoxifen would benefit from reliable and efficient synthetic access to the drug.

Telescoped Process to Manufacture 6,6,6-Trifluorofucose via Diastereoselective Transfer Hydrogenation: Scalable Access to an Inhibitor of Fucosylation Utilized in Monoclonal Antibody Production.

IgG1 monoclonal antibodies with reduced glycan fucosylation have been shown to improve antibody-dependent cellular cytotoxicity (ADCC) by allowing more effective binding of the Fc region of these proteins to T cells receptors. Increased in vivo efficacy in animal models and oncology clinical trials has been associated with the enhanced ADCC provided by these engineered mAbs. 6,6,6-Trifluorofucose (1) is a new inhibitor of fucosylation that has been demonstrated to allow the preparation of IgG1 monoclonal antibodies with lower fucosylation levels and thus improve the ADCC of these proteins.

Model system-based mechanistic studies of black tea thearubigin formation.

Thearubigins are the most abundant pigments found in black tea, comprising polyphenolic oxidation products, whose composition and chemical nature have remained unresolved until recently. In the course of studying the mechanism of thearubigin formation from green tea flavan-3-ols, a model system, based on electrochemical oxidation of one of the main tea flavan-3-ol substrates, epigallocatechin gallate (EGCG), was employed. Reaction intermediates and products were subsequently analysed using mass spectrometry techniques, allowing for the identification of key intermediates and products.

Identification of novel homologous series of polyhydroxylated theasinensins and theanaphthoquinones in the SII fraction of black tea thearubigins using ESI/HPLC tandem mass spectrometry.

Thearubigins are the most abundant phenolic pigments found in black tea, produced by enzymatic oxidation of green tea flavan-3-ols in tea fermentation of until recently unknown composition. In this study electrospray ionization tandem LC-MS(n) experiments have been applied for the characterization of crude thearubigins isolated from black tea not exceeding 1000 Da. The aim of this study is to confirm the oxidative cascade hypothesis of tea fermentation.

Investigation of processes in black tea manufacture through model fermentation (oxidation) experiments.

Flavanol depleted whole fresh green tea leaf powder, as reported in the literature, was used as matrix for a systematic study of the endogenous oxidative enzymatic conversion of selected flavanol combinations to theaflavins and thearubigins. The activity of the two crucial enzymes polyphenol oxidase (PPO) and peroxidase (POD) was controlled individually through addition of H2O2 and/or O2. Using the endogenous peroxidase only it was shown that (-)-epicatechin alone did not react with POD.

The Family Approach to the Resolution of Racemates .

The resolution of racemates is revolutionized with the method presented here, in which mixtures ("families") of structurally and stereochemically related resolving agents are used to precipitate salts of acidic or basic racemates rapidly and dependably. The racemate is usually separated in a single operation into enantiomers-the enantiomeric excesses and yields are good to excellent. Reagent mixtures with racemic or achiral components have also been developed.