We describe the successful synthesis of the phormidolide A macrocycle as a crucial step toward its total synthesis and configurational assignment. Exhaustive exploration of macrocyclization strategies revealed the detrimental effects of a bulky protecting group on the C17 hydroxyl function, leading to the successful use of a C17 -methoxybenzyloxymethyl (PMBM) ether in the macrolactonization reaction. Further elaboration of the macrocycle with a truncated C18-C23 side chain afforded an advanced C1-C23 fragment of phormidolide A.
View Article and Find Full Text PDFPhenotypic changes to endometrial epithelial cells underpin receptivity to embryo implantation at the onset of pregnancy but the effect of hyperglycemia on these processes remains poorly understood. Here, we show that physiological levels of glucose (5 mM) abolished receptivity in the endometrial epithelial cell line, Ishikawa. However, embryo attachment was supported by 17 mM glucose as a result of glucose flux through the hexosamine biosynthetic pathway (HBP) and modulation of cell function via protein O-GlcNAcylation.
View Article and Find Full Text PDFBackground: clinically silent cardiac sarcoidosis (CS) may be associated with adverse outcomes, hence the rationale for screening patients with extracardiac sarcoidosis. The optimal screening strategy has not been clearly defined.
Methods: patients with extra-cardiac sarcoidosis were prospectively included and underwent screening consisting of symptom history, electrocardiography (ECG), transthoracic echocardiogram, Holter, and signal-averaged ECG (SAECG).