[reaction: see text] A convergent synthesis of the E'FGH' ring fragment of ciguatoxin has been accomplished through (i) coupling between the E' ring-acetylide and the H' ring-aldehyde, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function, and (iv) reductive hydroxy-ketone cyclization to construct the G ring.
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http://dx.doi.org/10.1021/ol0256264 | DOI Listing |
Curr Top Dev Biol
January 2025
Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH, United States.
Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Molecular Synthesis Center, Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
2-Deoxy-β-glycosides are essential components of natural products and pharmaceuticals; however, the corresponding 2-deoxy-β-glycosidic bonds are challenging to chemically construct. Herein, we describe an efficient catalytic protocol for synthesizing 2-deoxy-β-glycosides via either IPrAuNTf-catalyzed activation of a unique 1,2--positioned C2--propargyl xanthate (OSPX) leaving group or (PhO)PAuNTf-catalyzed activation of a 1,2--C2--alkynylbenzoate (OABz) substituent of the corresponding thioglycosides. These activation processes trigger 1,2-alkyl/arylthio-migration glycosylation, enabling the synthesis of structurally diverse 2-deoxy-β-glycosides under mild reaction conditions.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Marine Microbiology and Biogeochemistry, Royal Netherlands Institute for Sea Research (NIOZ), Den Burg 1790 AB, The Netherlands.
Heterocytes, specialized cells for nitrogen fixation in cyanobacteria, are surrounded by heterocyte glycolipids (HGs), which contribute to protection of the nitrogenase enzyme from oxygen. Diverse HGs preserve in the sediment and have been widely used as evidence of past nitrogen fixation, and structural variation has been suggested to preserve taxonomic information and reflect paleoenvironmental conditions. Here, by comprehensive HG identification and screening of HG biosynthetic gene clusters throughout cyanobacteria, we reconstruct the convergent evolutionary history of HG structure, in which different clades produce the same HGs.
View Article and Find Full Text PDFSchizophr Bull
January 2025
Psychotic Disorders Division, McLean Hospital, Belmont, MA, United States.
Background And Hypothesis: Convergent evidence shows the presence of brain metabolic abnormalities in psychotic disorders. This study examined brain reductive stress and energy metabolism in people with psychotic disorders with impaired or average range cognition. We hypothesized that global cognitive impairment would be associated with greater brain metabolic dysregulation.
View Article and Find Full Text PDFBackground: Targeting glutamine metabolism has emerged as a promising strategy in cancer therapy. However, several barriers, such as anti-tumor efficacy, drug toxicity, and safety, remain to be overcome to achieve clinical utility. Prior preclinical studies had generated encouraging data showing promises of cancer metabolism targeting drugs, although most were performed on immune-deficient murine models.
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