Concerted Ring Opening and Cycloaddition of Chiral Epoxy Enolsilanes with Dienes.

Silyl-triflate-catalyzed (4+3) cycloadditions of epoxy enolsilanes with dienes provide a mild and chemoselective synthetic route to seven-membered carbocycles. Epoxy enolsilanes containing a terminal enolsilane and a single stereocenter undergo cycloaddition with almost complete conservation of enantiomeric purity, a finding that argues against the involvement of oxyallyl cation intermediates which have been previously proposed for these types of reactions. Reported are theoretical and experimental investigations of the cycloaddition mechanism. The major enantiomers of the cycloadducts are derived from S(N)2-like reactions of the silylated epoxide with the diene, in which stereospecific ring opening and formation of the two new C-C bonds occur in a single step. Calculations predict, and experiments confirm, that the observed small losses of enantiomeric purity are traced to a triflate-mediated double S(N)2 cycloaddition pathway.

Intermolecular (4+3) cycloadditions of aziridinyl enolsilanes.

Upon activation by strong Brønsted acids, aziridinyl enolsilanes undergo (4+3) cycloadditions with dienes to afford aminoalkylated cycloheptenones as products. The use of a highly polar medium such as nitroalkane facilitates high cycloaddition yields of up to 99%. Optically pure aziridinyl enolsilanes react to yield (4+3) cycloadducts with up to 99% ee.

Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis.

Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product. Across several cancer cell lines, we showed that alisol B-treated cells displayed an increase of autophagic flux and formation of autophagosomes, leading to cell cycle arrest at the G(1) phase and cell death. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, we showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase. This study provides detailed insights into the cytotoxic mechanism of a novel antitumor compound.

Inter- and intramolecular [4 + 3] cycloadditions using epoxy enol silanes as functionalized oxyallyl cation precursors.

Using epoxy enol triethylsilanes as oxyallyl cation precursors, [4 + 3] cycloadditions with various dienes occur under catalysis by silyl triflates and acids in good yields. The intramolecular [4 + 3] cycloaddition proceeds under mild conditions and generate hydroxylated cycloadducts with high diastereoselectivity and yields. Enantiomerically pure epoxy enol silanes have been shown to give excellent yields of the optically pure cycloadduct bearing multiple stereocenters.

Asymmetric total synthesis of (-)-indicol by a carbene cyclization-cycloaddition cascade strategy.

The first total synthesis of a secodolastane, (-)-indicol, has been accomplished. The key reaction is a rhodium(II)-mediated carbene cyclization-cycloaddition cascade, by which the core bicyclo[5.4.0]undecane skeleton was assembled. In this one-pot reaction, a domino series of transformations resulting in the construction of three sigma bonds and three stereocenters was realized in good yield.

Time-resolved resonance Raman observation of the 2-fluorenylnitrenium ion reaction with guanosine to form a C8 intermediate.

Time-resolved resonance Raman spectroscopy was used to directly observe the reaction of the 2-fluorenylnitrenium ion with guanosine to produce a C8 intermediate species. Comparison of the Raman spectra with results of density functional theory calculations indicates the C8 intermediate forms two C=N conjugated bonds in ring 1 of the guanosine moiety.