Correction: π-Facial selectivity in the Diels-Alder reaction of glucosamine-based chiral furans and maleimides.

Correction for 'π-Facial selectivity in the Diels-Alder reaction of glucosamine-based chiral furans and maleimides' by Cornelis H. M. van der Loo et al., Org. Biomol. Chem., 2023, 21, 1888-1894, https://doi.org/10.1039/D2OB02221D.

Substituted anilides from chitin-based 3-acetamido-furfural.

The synthesis of aromatic compounds from biomass-derived furans is a key strategy in the pursuit of a sustainable economy. Within this field, a Diels-Alder/aromatization cascade reaction with chitin-based furans is emerging as a powerful tool for the synthesis of nitrogen-containing aromatics. In this study we present the conversion of chitin-based 3-acetamido-furfural (3A5F) into an array of di- and tri-substituted anilides in good to high yields (62-90%) via a hydrazone mediated Diels-Alder/aromatization sequence. The addition of acetic anhydride expands the dienophile scope and improves yields. Moreover, replacing the typically used dimethyl hydrazone with its pyrrolidine analogue, shortens reaction times and further increases yields. The hydrazone auxiliary is readily converted into either an aldehyde or a nitrile group, thereby providing a plethora of functionalized anilides. The developed procedure was also applied to 3-acetamido-5-acetylfuran (3A5AF) to successfully prepare a phthalimide.

π-Facial selectivity in the Diels-Alder reaction of glucosamine-based chiral furans and maleimides.

Furans derived from carbohydrate feedstocks are a versatile class of bio-renewable building blocks and have been used extensively to access 7-oxanorbornenes via Diels-Alder reactions. Due to their substitution patterns these furans typically have two different π-faces and therefore furnish racemates in [4 + 2]-cycloadditions. We report the use of an enantiopure glucosamine derived furan that under kinetic conditions predominantly affords the exo-product with a high π-face selectivity of 6.5 : 1. The structure of the product has been resolved unequivocally by X-ray crystallography, and a multi-gram synthesis (2.8 g, 58% yield) confirms the facile accessibility of this multifunctional enantiopure building block.

The dehydration of N-acetylglucosamine (GlcNAc) to enantiopure dihydroxyethyl acetamidofuran (Di-HAF).

The first multi-gram synthesis of enantiopure dihydroxyethyl acetamidofuran (Di-HAF) is reported. Under optimized conditions, GlcNAc dehydrates in pyridine in the presence of phenylboronic acid and triflic acid to afford Di-HAF in 73% yield and 99.3% ee in just 30 minutes. This protocol opens the door for further research on this bio-renewable building block which is now available as a chiral pool synthon. A plausible mechanism of its formation and of the subsequent dehydration of Di-HAF into well-known 3-acetamido-5-acetylfuran (3A5AF) is proposed.

Polycyclic Sulfoximines as New Scaffolds for Drug Discovery.

The design and synthesis of three novel polycyclic scaffolds containing sulfoximines are presented in this work, which exemplify that sulfoximines represent a real opportunity for the discovery of new drug candidates. Additionally, the structures present at least two points of diversification and contain a high level of sp3-character, hence being very interesting 3D scaffolds. The compounds synthesized were added to the compound collection of the European Lead Factory.

Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory Perspective.

High-throughput screening (HTS) represents a major cornerstone of drug discovery. The availability of an innovative, relevant and high-quality compound collection to be screened often dictates the final fate of a drug discovery campaign. Given that the chemical space to be sampled in research programs is practically infinite and sparsely populated, significant efforts and resources need to be invested in the generation and maintenance of a competitive compound collection. The European Lead Factory (ELF) project is addressing this challenge by leveraging the diverse experience and know-how of academic groups and small and medium enterprises (SMEs) engaged in synthetic and/or medicinal chemistry. Here, we describe the novelty, diversity, structural complexity, physicochemical characteristics and overall attractiveness of this first batch of ELF compounds for HTS purposes.

Resolution of praziquantel.

BACKGROUND: Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill. METHODOLOGY/PRINCIPAL FINDINGS: We have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself. CONCLUSIONS/SIGNIFICANCE: Both resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidation of the drug's mechanism of action.