Vicinal ketoesters - key intermediates in the total synthesis of natural products.

This review summarizes examples for the application of vicinal ketoesters such as α-ketoesters, mesoxalic esters, and α,β-diketoesters as key intermediates in the total synthesis of natural products utilizing their electrophilic keto group as reactive site. Suitable key reactions are, e.g.

Preussochromone Puzzle: Structural Revision of Preussochromones E and F by Total Synthesis.

A stereoselective synthesis of the proposed and actual structures of the natural products preussochromones E and F is reported. The key step is a ring-closing metathesis to close the five-membered ring and install the trans configuration of the annulated five-six ring system. The analysis of the NMR couplings of the isolated natural product with the synthesized compound revealed its real structure with a cis annulation, which could also be synthesized using an intramolecular aldol reaction of a -tricarbonyl compound.

Total Synthesis of (-)-Preussochromone A.

An enantioselective total synthesis of the natural product (-)-preussochromone A is reported. The tricyclic thiopyrane skeleton could be assembled via Lewis acid-mediated cycloisomerization of a precursor with a 2-thiochromenone substructure and an α-ketoester moiety. The chromenone core was synthesized by cyclization of a dithioketene acetal and oxidation to a 2-sulfonylchromenone to set up the subsequent thia-Michael--Michael addition of an aliphatic thiol producing the highly oxidized side chain.

CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study.

Objectives: The Preemptive Pharmacogenetic-guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) pilot trial aims to use existing institutional resources to develop a process for integrating CYP2D6 pharmacogenetic test results into the patient electronic health record, to develop an evidence-based clinical decision support tool to facilitate CYP2D6 genotype-guided metoprolol administration in the cardiac surgery setting, and to determine the impact of implementing this CYP2D6 genotype-guided integrated approach on the incidence of postoperative atrial fibrillation (AF), provider, and cost outcomes.

Design: One-arm Bayesian adaptive design clinical trial.

Setting: Single center, university hospital.

Electronic health record design and implementation for pharmacogenomics: a local perspective.

Purpose: The design of electronic health records to translate genomic medicine into clinical care is crucial to successful introduction of new genomic services, yet there are few published guides to implementation.

Methods: The design, implemented features, and evolution of a locally developed electronic health record that supports a large pharmacogenomics program at a tertiary-care academic medical center was tracked over a 4-year development period.

Results: Developers and program staff created electronic health record mechanisms for ordering a pharmacogenomics panel in advance of clinical need (preemptive genotyping) and in response to a specific drug indication.

The Pharmacogenomics Research Network Translational Pharmacogenetics Program: overcoming challenges of real-world implementation.

The pace of discovery of potentially actionable pharmacogenetic variants has increased dramatically in recent years. However, the implementation of this new knowledge for individualized patient care has been slow. The Pharmacogenomics Research Network (PGRN) Translational Pharmacogenetics Program seeks to identify barriers and develop real-world solutions to implementation of evidence-based pharmacogenetic tests in diverse health-care settings.