Latest Advances Towards Ras Inhibition: A Medicinal Chemistry Perspective

Owing to their high occurrence rate across many human cancers and their lack of druggability so far, mutant forms of the signaling protein Ras are currently among the most attractive (and elusive) oncology targets. This strong appeal explains the sustained effort in the field, and the ensuing progress has rekindled optimism regarding the discovery of Ras inhibitors. In this Minireview, we discuss the most recent advances towards irreversible inhibitors, and highlight approaches to inhibitors of Ras–effector interactions that have been overshadowed by the current focus on direct Ras inhibition. At the same time, we provide a critical assessment from a medicinal chemistry perspective.     

The oxa-Michael reaction: from recent developments to applications in natural product synthesis

In marked contrast to Michael reactions, oxa-Michael reactions have not been used as standard transformations in organic synthesis until quite recently. This was mainly due to a lack of reactivity and selectivity, although the potential products of such reactions are valuable intermediates. This tutorial review presents recent major advances in the field of oxa-Michael (sometimes called oxo-Michael or oxy-Michael) reactions and applications in the total synthesis of complex natural products.     

Recent developments in the total synthesis of fungicidal natural products--a crop protection perspective

Natural products play an important role as lead structures for the identification of novel active ingredients in crop protection. As it is the case in the pharmaceutical industry, however, many crop protection companies have substantially decreased their in-house efforts in natural product exploration. Therefore, joint projects with academic research groups become more and more important in the field. This review describes several examples for successful collaborations in the field of fungicidal natural products.     

Diastereoselective synthesis of highly functionalized tetrahydroxanthenols--unprecedented access to privileged structural motifs

Tetrahydroxanthenones, which can be easily prepared by a domino oxa-Michael aldol condensation, offer various possibilities for diastereoselective functionalization, giving access to the stereocontrolled synthesis of stereochemical triades or tetrades, which represent privileged structural motifs. In most cases, the relative stereochemistry was unequivocally established by crystal structure analysis.     

Recent developments in the field of oxa-Michael reactions

Oxa-Michael reactions, i.e. addition reactions of oxygen nucleophiles to conjugated systems, have traditionally received much less attention from the scientific community compared to the addition of carbon nucleophiles to conjugate acceptor systems (Michael reaction). This was mainly due to lack of reactivity and selectivity of these reactions. Within the last few years however, there has been a remarkable increase in publications focussing on method development as well as applications to natural product synthesis. This tutorial review discusses instructive examples that have substantially broadened the scope of oxa-Michael reactions.     

Recent Advances in Modern Static Devolatilization

Summary: The present paper deals with state-of-the-art static devolatilization technology for polymer melts. Recent results obtained by CFD-studies as well as by experimental testing at pilot scale are presented for the devolatilization of technical thermoplasts like polystyrene, poly (methyl methacrylate) and polycarbonate. It is shown that with the correct design of preheater and devolatilization chamber, volatiles like monomers and solvents can be efficiently removed from the polymer melt, both from the economical and technological point of view. As design criteria for the preheater, maldistribution and heat transfer efficiency are explained in detail.