ABSTRACT
The non-aldol aldol reaction of the isomeric epoxy silyl ethers is controlled by the conformation of the transition states leading to an internal hydride shift. One isomer rearranges to the ß-silyloxy ketone whereas the other isomer gives a ß-elimination product. Theoretical calculations show that the substrates with substituents that favor the formation of the chairlike transition state rearrange normally while those that do not undergo elimination instead.
Subject(s)
Aldehydes/chemistry , Epoxy Compounds/chemistry , Ketones/chemistry , Models, Theoretical , Molecular Structure , Silanes/chemistry , StereoisomerismABSTRACT
A new synthesis of dibenzopyranones 14 is reported via the Diels-Alder cycloaddition of 4-cyanocoumarins 12 with 1-silyloxydienes 10 to give the adducts 13 which are then converted into 14 in one step via treatment with base and loss of the cyano and silyloxy groups.
Subject(s)
Benzopyrans/chemical synthesis , Coumarins/chemistry , Alkenes/chemistry , Benzopyrans/chemistry , Cyclization , Molecular StructureABSTRACT
Silyl triflate-promoted rearrangement of cis-2,3-epoxycycloalkanols A, prepared by epoxidation of the cyclic allylic alcohol and then silylation, afforded good yields ( approximately 70-75%) of the cis-2-alkyl-3-silyloxycycloalkanones B, presumably via the intermediates C and D, even with quite large alpha-substituents, e.g., tert-butyl. Finally, it has been shown that the stereochemistry of the epoxy alcohol is crucial as one would expect from the mechanism.
Subject(s)
Epoxy Compounds/chemistry , Ketones/chemical synthesis , Silanes/chemical synthesis , Ketones/chemistry , Molecular Conformation , Silanes/chemistry , StereoisomerismABSTRACT
Efficient internalization of proteins from the cell surface is essential for regulating cell growth and differentiation. In a screen for yeast mutants defective in ligand-stimulated internalization of the alpha-factor receptor, we identified a mutant allele of TOR2, tor2G2128R. Tor proteins are known to function in translation initiation and nutrient sensing and are required for cell cycle progression through G1. Yeast Tor2 has an additional role in regulating the integrity of the cell wall by activating the Rho1 guanine nucleotide exchange factor Rom2. The endocytic defect in tor2G2128R cells is due to disruption of this Tor2 unique function. Other proteins important for cell integrity, Rom2 and the cell integrity sensor Wsc1, are also required for efficient endocytosis. A rho1 mutant specifically defective in activation of the glucan synthase Fks1/2 does not internalize alpha-factor efficiently, and fks1Delta cells exhibit a similar phenotype. Removal of the cell wall does not inhibit internalization, suggesting that the function of Rho1 and Fks1 in endocytosis is not through cell wall synthesis or structural integrity. These findings reveal a novel function for the Tor2-Rho1 pathway in controlling endocytosis in yeast, a function that is mediated in part through the plasma membrane protein Fks1.
Subject(s)
Cell Membrane/metabolism , Endocytosis/physiology , Guanine Nucleotide Exchange Factors , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/metabolism , rho GTP-Binding Proteins/metabolism , Cell Cycle Proteins , Cell Differentiation , Cell Membrane/physiology , Cell Wall/metabolism , Cell Wall/physiology , Cloning, Molecular , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/physiology , G1 Phase , Mutation , Phosphatidylinositol 3-Kinases , Phosphotransferases (Alcohol Group Acceptor)/physiology , Protein Biosynthesis , Saccharomyces cerevisiae/physiology , Signal Transduction , rho GTP-Binding Proteins/physiologyABSTRACT
Internalization of activated signaling receptors by endocytosis is one way cells downregulate extracellular signals. Like many signaling receptors, the yeast alpha-factor pheromone receptor is downregulated by hyperphosphorylation, ubiquitination, and subsequent internalization and degradation in the lysosome-like vacuole. In a screen to detect proteins involved in ubiquitin-dependent receptor internalization, we identified the sphingoid base-regulated serine-threonine kinase Ypk1. Ypk1 is a homologue of the mammalian serum- and glucocorticoid-induced kinase, SGK, which can substitute for Ypk1 function in yeast. The kinase activity of Ypk1 is required for receptor endocytosis because mutations in two residues important for its catalytic activity cause a severe defect in alpha-factor internalization. Ypk1 is required for both receptor-mediated and fluid-phase endocytosis, and is not necessary for receptor phosphorylation or ubiquitination. Ypk1 itself is phosphorylated by Pkh kinases, homologues of mammalian PDK1. The threonine in Ypk1 that is phosphorylated by Pkh1 is required for efficient endocytosis, and pkh mutant cells are defective in alpha-factor internalization and fluid-phase endocytosis. These observations demonstrate that Ypk1 acts downstream of the Pkh kinases to control endocytosis by phosphorylating components of the endocytic machinery.
