Evaluating New Chemistry to Drive Molecular Discovery: Fit for Purpose?

As our understanding of the impact of specific molecular properties on applications in discovery-based disciplines improves, the extent to which published synthetic methods meet (or do not meet) desirable criteria is ever clearer. Herein, we show how the application of simple (and in many cases freely available) computational tools can be used to develop a semiquantitative understanding of the potential of new methods to support molecular discovery. This analysis can, among other things, inform the design of improved substrate scoping studies; direct the prioritization of specific exemplar structures for synthesis; and substantiate claims of potential future applications for new methods

Evaluierung neuer Reaktionen zur Steuerung der Wirkstoff‐Forschung: ein Eignungstest

Mit der Verbesserung unserer Kenntnisse zur Bedeutung bestimmter Moleküleigenschaften bei Anwendungen im Rahmen der Wirkstoffsuche wird das Ausmaß immer klarer, in dem veröffentlichte Synthesemethoden erwünschten Kriterien genügen (oder nicht genügen). Wir beschreiben hier, wie die Anwendung einfacher (und in vielen Fällen frei verfügbarer) Rechenprogramme genutzt werden kann, um ein semiquantitatives Verständnis des Potenzials von neuen Methoden in der Wirkstoff‐Forschung zu entwickeln. Diese Analyse kann sich unter anderem auf die Planung verbesserter Studien zum Substratspektrum auswirken, die Priorisierung von bestimmten Beispielstrukturen für die Synthese leiten und Ansprüche für potenzielle künftige Anwendungen von neuen Methoden begründen

Cyanoguanidine as a versatile, eco-friendly and inexpensive reagent for the synthesis of 2-aminobenzoxazoles and 2-guanidinobenzoxazoles

International audienc

Synthesis and X-ray structure analysis of cytotoxic heptacoordinate sulfonamide salan titanium(IV)-bis-chelates

A series of novel sulfonamide substituted heteroleptic salan titanium(iv)-bis-chelates complexed to 2,6-pyridinedicarboxylic acid were synthesized, structurally characterized and evaluated for their anticancer activity against two human carcinoma cell lines. All cytotoxic complexes showed complete inhibition of cell growth at active concentration, two complexes based on pyrrolidine and azepane substituted sulfonamides displayed IC50 values below 1.7 μM and are more cytotoxic than cisplatin in both tested cell lines. The azepane substituted complex exhibited excellent activity with an IC50 value of 0.5 ± 0.1 μM in Hela S3 and 1.0 ± 0.1 μM in Hep G2.publishe

Perspectives of Alkyl Introduction into Methylene-Containing Heterocycles

Two-step α-methylation via enamination with subsequent reduction was investigated on various methylene-containing heterocyclic carbonyl compounds including lactams, lactones, thiolactones etc. Outcomes or enamination with Bredereck’s reagent and DMF-DMA were compared. Optimal enamination and reduction protocols regarding solubility, reactivity and thermal stability of the substrates were elaborated. The construction of primary and secondary alkyl substituents through enaminone interaction with organometallic reagents was tested

Practical One Pot Synthesis of 2-Alkyl-substituted Benzothiazoles from Bis-(2-nitrophenyl)-disulfides.

2-Methyl benzothiazoles are widely used as key precursor for dyes, photosensitizers and fluorescent markers. Therefore, they are demanded in multigram and even kilogram amounts. Hereby, we propose a scalable single-step procedure for production of 2-alkylsubstituted benzothiazoles from corresponding bis-(2-nitrophenyl)-disulfides. Substrates containing various substituents including carboxylic and ester groups were introduced into reaction. Different sodium salts were tested as reducing agents, extensive optimization was performed. The products were obtained in the amounts of up to 350 g in a single run