7 research outputs found
Homologation of the Fischer Indolization: A Quinoline Synthesis via Homo‐Diaza‐Cope Rearrangement
We disclose a new Brønsted acid promoted quinoline synthesis, proceeding via homo‐diaza‐Cope rearrangement of N‐aryl‐N′‐cyclopropyl hydrazines. Our strategy can be considered a homologation of Fischer's classical indole synthesis and delivers 6‐membered N‐heterocycles, including previously inaccessible pyridine derivatives. This approach can also be used as a pyridannulation methodology toward constructing polycyclic polyheteroaromatics. A computational analysis has been employed to probe plausible activation modes and to interrogate the role of the catalyst
Direct and Catalytic C-Glycosylation of Arenes: Expeditious Synthesis of the Remdesivir Nucleoside
Since early 2020, scientists have strived to find an effective solution to fight SARS-CoV-2, especially by developing reliable vaccines that inhibit the spread of the disease and repurposing drugs for combatting its effects on the human body. The antiviral prodrug Remdesivir is still the most widely used therapeutic during the early stage of the infection. However, the current synthetic routes rely on the use of protecting groups, air-sensitive reagents, and cryogenic conditions, impeding the cost-efficient supply to patients. We therefore focused on the development of a straightforward, direct addition of (hetero)arenes to unprotected sugars. Here we report a silylium-catalyzed and completely stereoselective C -glycosylation that initially yields the open-chain polyols, which can be selectively cyclized to provide either the kinetic α-furanose or the thermodynamically favored β-anomer. The method significantly expedites the synthesis of Remdesivir precursor GS-441524 after subsequent Mn-catalyzed C–H oxidation and deoxycyanation
Unified Approach to Imidodiphosphate-Type Brønsted Acids with Tunable Confinement and Acidity
We have designed and realized an efficient and operationally simple single-flask synthesis of imidodiphosphate-based Brønsted acids. The methodology proceeds via consecutive chloride substitutions of hexachlorobisphosphazonium salts, providing rapid access to imidodiphosphates (IDP), iminoimidodiphosphates (iIDP), and imidodiphosphorimidates (IDPi). These privileged acid catalysts feature a broad acidity range (pKa from ∼11 to 95:5 er) sulfoxidation of methyl n-propyl sulfide. Furthermore, the methodology delivers a novel, rationally designed super acidic catalyst motif, imidodiphosphorbis(iminosulfonylimino)imidate (IDPii), the extreme reactivity of which exceeds commonly employed super-Brønsted acids, such as trifluoromethanesulfonic acid. The unique reactivity of one such IDPii catalyst has been demonstrated in the first α-methylation of a silyl ketene acetal with methanol as the electrophilic alkylating reagent
Strong and Confined Acids in Asymmetric Catalysis
This work focuses on the conceptual development of highly confined, super acidic Brønsted acids and their application in asymmetric catalysis. A new synthetic strategy to access imidodiphosphate-derived Brønsted acids based on a toolbox principle has been developed. This methodology proceeds via consecutive chloride substitutions of hexachlorobisphosphazonium salts, providing rapid access to privileged catalyst motifs, such as imidodiphosphates (IDP), iminoimidodiphosphates (iIDP), and imidodiphosphorimidates (IDPi). Furthermore, this approach enables access to previously elusive catalyst scaffolds with particularly high structural confinement, allowing the highly enantioselective transformation of small and structurally unbiased substrates, as exemplarily demonstrated in the asymmetric sulfoxidation of propyl methyl sulfide. To access extremely acidic catalyst motifs, a new synthesis of arylbis(trifluoromethylsulfonylimino)sulfonamides has been developed, which upon implementation into the imidodiphosphate-framework led to the development of imidodiphosphorbis(iminosulfonylimino)imidates (IDPii). Combinatorial spectroscopic and experimental data reveal higher acidities of the novel IDPii motif than commonly employed super acids, such as trifluoromethanesulfonic acid or bis(trifluoromethanesulfonyl)imide. Most notably, IDPiis allow rendering alcohols into strong electrophilic alkylating reagents under silylium activation, as it has been exemplarily demonstrated in the α-methylation of silyl ketene acetals – transforming methanol into a strong electrophilic methyl surrogate. Although the IDPii catalyst class displays extreme reactivity and overcomes previous limitations regarding substrate activation, no sufficient enantioinduction was observed in the explored asymmetric transformations. Crystallographic analyses of several IDPii catalysts motifs illustrated insufficient BINOL-induced structural confinement. Considered as a solution, a monovalent chiral catalyst scaffold has been conceptually designed, which in combination with the new access of bis(trifluoromethylsulfonylimino)sulfonyl units was believed to give access to a novel extremely Brønsted acidic and highly selective catalyst class. This catalyst design focuses on the tetrahydroindacene motif with two adjacent appendages to confine the active site. Herein, a seminal contribution toward the conceptual design, the synthesis and potential application of this unprecedented catalyst scaffold is disclosed
A review of bioinformatics platforms for comparative genomics. Recent developments of the EDGAR 2.0 platform and its utility for taxonomic and phylogenetic studies
Yu J, Blom J, Glaeser SP, et al. A review of bioinformatics platforms for comparative genomics. Recent developments of the EDGAR 2.0 platform and its utility for taxonomic and phylogenetic studies. Journal of Biotechnology. 2017;261:2-9.The rapid development of next generation sequencing technology has greatly increased the amount of available microbial genomes. As a result of this development, there is a rising demand for fast and automated approaches in analyzing these genomes in a comparative way. Whole genome sequencing also bears a huge potential for obtaining a higher resolution in phylogenetic and taxonomic classification. During the last decade, several software tools and platforms have been developed in the field of comparative genomics. In this manuscript, we review the most commonly used platforms and approaches for ortholog group analyses with a focus on their potential for phylogenetic and taxonomic research. Furthermore, we describe the latest improvements of the EDGAR platform for comparative genome analyses and present recent examples of its application for the phylogenomic analysis of different taxa. Finally, we illustrate the role of the EDGAR platform as part of the BiGi Center for Microbial Bioinformatics within the German network on Bioinformatics Infrastructure (de.NBI)