Total Asymmetric Synthesis of Glycomimetics and Polypropionates of Biological Interest

Using readily available chiral auxiliaries such as (+)- and (?)-camphanic acid, (R,R)- and (S,S)-tartaric acid derivatives (e.g. RADO(R)-COCl, SADO(R)-COCl) efficient diastereoselective syntheses of rare sugars and glycomimetics have been developed. They engage the 'naked sugar' (enantiomerically pure 7-oxanorbornene) methodologies in which the chiral auxiliaries are recovered at an early stage of the multistep syntheses. A new reaction cascade starting with the hetero-Diels-Alder addition of sulfur dioxide to 1-(1-phenylethoxy)-1,3-dienes derived from inexpensive (+)- and (?)-1-phenylethanol allows the one-pot, four-component synthesis of polyfunctional sulfones, sulfonamides and sulfonic esters containing up to three stereogenic centers. The method ensures a high molecular and stereochemical diversity. The reaction cascade can also produce polyketide and polypropionate fragments in one-pot operations. The latter contain up to three contiguous stereogenic centers and do not have to be modified (deprotection, activation) before using them as nucleophilic partners in diastereoselective cross-aldol reactions, thus permitting the quick access to complicated polypropionate antibiotics such as Baconipyrones, Ryfamicyn S and Apoptolidines

Research Topics

Quantum-mechanical calculations have been applied to predict thermodynamic and reactivity properties of unknown organic molecules, being stable compounds or reactive intermediates. Through synthesis some of the theoretical systems become real compounds that can be synthons (synthetic intermediates) or chirons (optically pure synthetic intermediates) useful in the preparation of natural products and analogues of biological interest (anti-cancer, anti-virus, antibiotic, anti-diabetes agents). Our interests concentrate on remote substituent effects as we want to play with them together with polyfunctional systems and reactions that constitute new synthetic approaches. These have to be convergent, highly stereoselective, and versatile (applicable to a large variety of derivatives: molecular diversity). We often rely on tandem reactions or/and reaction cascades. Sometimes the new compounds and their new reactions send us back to the theory and to mechanistic studies

Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved

Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The summary relative risk of colon cancer was 1.18 [95%C.I.: 1.06-1.32] for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative pre-cancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicit

La pollution par les composés fluorés et ses effets sur les arbres fruitiers du Valais

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A deep dive into fat: Investigating blubber lipidomic fingerprint of killer whales and humpback whales in northern Norway

In cetaceans, blubber is the primary and largest lipid body reservoir. Our current understanding about lipid stores and uses in cetaceans is still limited, and most studies only focused on a single narrow snapshot of the lipidome. We documented an extended lipidomic fingerprint in two cetacean species present in northern Norway during wintertime. We were able to detect 817 molecular lipid species in blubber of killer whales (Orcinus orca) and humpback whales (Megaptera novaeangliae). The profiles were largely dominated by triradylglycerols in both species and, to a lesser extent, by other constituents including glycerophosphocholines, phosphosphingolipids, glycerophosphoethanolamines, and diradylglycerols. Through a unique combination of traditional statistical approaches, together with a novel bioinformatic tool (LION/web), we showed contrasting fingerprint composition between species. The higher content of triradylglycerols in humpback whales is necessary to fuel their upcoming half a year fasting and energy-demanding migration between feeding and breeding grounds. In adipocytes, we assume that the intense feeding rate of humpback whales prior to migration translates into an important accumulation of triacylglycerol content in lipid droplets. Upstream, the endoplasmic reticulum is operating at full capacity to supply acute lipid storage, consistent with the reported enrichment of glycerophosphocholines in humpback whales, major components of the endoplasmic reticulum. There was also an enrichment of membrane components, which translates into higher sphingolipid content in the lipidome of killer whales, potentially as a structural adaptation for their higher hydrodynamic performance. Finally, the presence of both lipid-enriched and lipid-depleted individuals within the killer whale population in Norway suggests dietary specialization, consistent with significant differences in δ15N and δ13C isotopic ratios in skin between the two groups, with higher values and a wider niche for the lipid-enriched individuals. Results suggest the lipid-depleted killer whales were herring specialists, while the lipid-enriched individuals might feed on both herrings and seals