A practical total synthesis of hapalosin, a 12-membered cyclic depsipeptide with multidrug resistance-reversing activity, by employing improved segment coupling and macrolactonization

A practical total synthesis of hapalosin, a compound with multidrug resistance-reversing activity, has been carried out using an unprecedented macrolactonization strategy. One of the features of the new approach is the straightforward and fully stereocontrolled access to the key gamma-amino beta-hydroxy carboxylic acid subunit via an efficient acetate aldol addition reaction with N-methyl alpha-aminoaldehydes, which relies on a camphor-derived chiral lithium acetate enolate reagent. The scope of this aldol reaction is investigated and its potential application to the synthesis of other structurally related, biologically relevant compounds illustrated. Remarkably, the chiral tether in the resulting gamma-amino aldol adducts sterically protect the carbonyl group, thus avoiding intramolecular cyclization during the amino group deprotection and the subsequent segment coupling event. After successful segment coupling and smooth, clean release of the chiral auxiliary, a new macrolactonization protocol, based on the principle of double activation of both reactive sites, is applied, which leads to the 12-membered macrolactone hapalosin in unprecedented chemical efficiency.     

Improvements in the methylmercury extraction from human hair by headspace solid-phase microextraction followed by gas-chromatography cold-vapour atomic fluorescence spectrometry

Improvements in the methylmercury extraction from human hair by solid-phase microextraction followed by gas chromatography coupled to cold-vapour atomic fluorescence spectrometry (GC-CVAFS) have been carried out. They consisted in the optimisation of the digestion step prior to the aqueous-phase ethylation and in the GC-CVAFS interface set-up. The main digestion parameters such as acid type, concentration, temperature and time have been optimised for hair sample analysis, thereby avoiding methylmercury degradation. Moreover, the stability of the digested samples was evaluated to improve the sample throughput.     

Catalytic Michael reactions of ketoesters with a camphor-derived acrylate equivalent: stereoselective access to all-carbon quaternary centers

A camphor-based alpha'-hydroxy enone reagent acts as a chiral acrylate equivalent in copper-catalyzed Michael reactions of beta-keto esters and affords products that possess all-carbon quaternary stereocenters of high enantiomeric purity.     

Enantioselective Addition of Alkynyl Ketones to Nitroolefins Assisted by Brønsted Base/H-Bonding Catalysis

Various sets of enolizable alkynyl ketones (including methyl ynones with α-aryl, α-alkenyl, and α-alkoxy groups) were able to react smoothly with nitroolefins with the assistance of bifunctional Brønsted base/H-bond catalysts to provide adducts with two consecutive tertiary stereocenters in a highly diastereo- and enantioselective fashion. Further transformation of the obtained adducts into optically active acyclic and polycyclic molecules, including some with intricate carbon skeletons, was also demonstrated.     

Quantitative evaluation of bias in PCR amplification and next-generation sequencing derived from metabarcoding samples

Unbiased identification of organisms by PCR reactions using universal primers followed by DNA sequencing assumes positive amplification. We used six universal loci spanning 48 plant species and quantified the bias at each step of the identification process from end point PCR to next-generation sequencing. End point amplification was significantly different for single loci and between species. Quantitative PCR revealed that Cq threshold for various loci, even within a single DNA extraction, showed 2,000-fold differences in DNA quantity after amplification. Next-generation sequencing (NGS) experiments in nine species showed significant biases towards species and specific loci using adaptor-specific primers. NGS sequencing bias may be predicted to some extent by the Cq values of qPCR amplification.     

Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins

The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR. The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses. The interaction of the RBD ¹³C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR. In particular, ¹⁵N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed. Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case. Based on these findings, 3D models of the interacting complexes have been proposed.     

Alpha'-hydroxy enones as achiral templates for Lewis acid-catalyzed enantioselective Diels-Alder reactions

alpha'-Hydroxy enones react with dienes in the presence of (S,S)-[Cu(tBu-box)](OTf)2 or (S,S)-[Cu(tBu-box)](SbF6)2 (2 to 10 mol %) to afford the corresponding Diels-Alder adducts in high yield and selectivity. Isomeric ratios (regioselectivity, endo/exo or cis/trans) of up to >99:1 and ee values of up to >99% are obtained. Significantly, difficult dienes such as isoprene, 2,3-dimethyl butadiene and piperylene behave satisfactorily. Subsequent oxidative cleavage of the ketol in the resulting cycloadducts by treatment with cerium ammonium nitrate (CAN) yields the corresponding enantiopure carboxylic acids. Alternatively, carbonyl addition and subsequent diol cleavage with CAN produces the corresponding ketone adducts.     

Varied Meanings and Engagement in School Mathematics: Cross‐Case Analysis of Three High‐Achieving Young Adolescent Girls

This paper presents an in‐depth cross‐case analysis of three high‐achieving young adolescent girls who had contrasting mathematics learning experiences during the first year of middle school. In particular, this study examines the foundation for their motivation, as well as the dominant mode of learning and academic engagement in relation to three sociocultural factors, family background, the role of peers, and the level of teachers' understanding of the students and instructional support provided. Our data analysis revealed that the three girls possessed motivation structures and learning dispositions that are more or less prone to conceptual or procedural understanding in mathematics. This resulted in a significant variation in the mode of their academic engagement with the subject, and this provided a different set of challenges in each girl's pursuit of higher level of mathematics learning.