Drug discovery from Nature: automated high-quality sample preparation

Secondary metabolites from plants, animals and microorganisms have been proven to be an outstanding source for new and innovative drugs and show a striking structural diversity that supplements chemically synthesized compounds or libraries in drug discovery programs. Unfortunately, extracts from natural sources are usually complex mixtures of compounds:: often generated in time consuming and for the most part manual processes. As quality and quantity of the provided samples play a pivotal role in the success of high-throughput screening programs this poses serious problems. In order to make samples of natural origin competitive with synthetic compound libraries, we devised a novel, automated sample preparation procedure based on solid-phase extraction (SPE). By making use of a modified Zymark RapidTrace® SPE workstation an easy-to-handle and effective fractionation method has been developed which allows the generation of highquality samples from natural origin, fulfilling the requirements of an integration into high-throughput screening programs

Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib) and Other Salinosporamides

The salinosporamides are potent proteasome inhibitors among which the parent marine-derived natural product salinosporamide A (marizomib; NPI-0052; 1) is currently in clinical trials for the treatment of various cancers. Methods to generate this class of compounds include fermentation and natural products chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis. The end products range from biochemical tools for probing mechanism of action to clinical trials materials; in turn, the considerable efforts to produce the target molecules have expanded the technologies used to generate them. Here, the full complement of methods is reviewed, reflecting remarkable contributions from scientists of various disciplines over a period of 7 years since the first publication of the structure of 1

Eignung der IFRS für Controllingzwecke – Ergebnisse einer empirischen Befragung nicht kapitalmarktorientierter Unternehmen

Mit der Entwicklung eines modifizierten IFRS für kleine und mittelgroße Unternehmen (IFRS for SMEs) durch das IASB soll nicht kapitalmarktorientierten Unternehmen die Anwendung der IFRS erleichtert werden. Da auch in mittelständischen Unternehmen die Integration von externem und internem Rechnungswesen ein wichtiges Motiv für die freiwillige Umstellung der Rechnungslegung von HGB auf IFRS ist, untersucht der vorliegende Beitrag, wie nicht kapitalmarktorientierte Unternehmen den Nutzen spezifischer Rechnungslegungsmethoden des vom IASB in Entwurfsfassung vorgelegten ED-IFRS for SMEs für unternehmensinterne Informations- und Steuerungszwecke einschätzen