In the past a variety of electron binding motifs has been identified for sodium chloride cluster anions. As for all of these clusters the excess electron is predicted to be bound in self-consistent-field calculations, the different binding mechanisms can be understood in terms of a one-electron potential largely due to the permanent multipole moments of the neutral cluster. Here we investigate a new class of (NaCl)(N)(-) anion that is predicted to be bound only after electron correlation has been taken into account. Correlation-bound states of the trimer, (NaCl)(3)(-), and tetramer, (NaCl)(4)(-), are characterized using Green's function and an equation-of-motion coupled-cluster method, and the computed electron binding energies as well as the distributions of the excess electrons as inferred from natural orbitals of the coupled-cluster calculations are compared with that of dipole-bound, quadrupole-bound, and defectlike (NaCl)(N)(-) anions. For the (NaCl)(4)(-) tetramer anion the correlation-bound state is predicted to represent the most stable isomer. Our results provide a sensitive test case for the development of improved one-electron model potentials for excess electrons bound to alkali halide clusters, and suggest that cluster abundance as inferred from peak intensities of photoelectron spectra is not directly related to the relative stability of the clusters.

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A Cu(II)-catalyzed diastereoselective Michael/aldol cascade approach is used to accomplish concise total syntheses of cardiotonic steroids with varying degrees of oxygenation including cardenolides ouabagenin, sarmentologenin, 19-hydroxysarmentogenin, and 5-epi-panogenin. These syntheses enabled the subsequent SAR studies on 37 synthetic and natural steroids to elucidate the effect of oxygenation, stereochemistry, C3-glycosylation and C17-heterocyclic ring. Based on this parallel evaluation of synthetic and natural steroids and their derivatives, glycosylated steroids cannogenol-L-α-rhamnoside (79a), strophanthidol-L-α-rhamnoside (92), and digitoxigenin-L-α-rhamnoside (97) were identified as the most potent steroids demonstrating broad anticancer activity at 10–100 nM concentrations and selectivity (nontoxic at 3 μM against NIH-3T3, MEF and developing fish embryos). Further analyses indicate that these molecules show a general mode of anticancer activity involving DNA damage upregulation that subsequently induces apoptosis.

The real mechanism of the Skraup-Doebner-Von Miller quinoline synthesis remains controversial and not well understood despite several mechanistic studies reported on the matter. A series of unexpected and unusual 5,6,7,8,9,10-hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-tetrahydro-4,4-tetramethylene-1H-cyclopenta[c]quinolines have been obtained through the Skraup-Doebner-Von Miller quinoline synthesis. On the basis of these unexpected results and in agreement with some of the previously reported quinoline syntheses, an alternative mechanistic pathway is proposed for this variant of the reaction. It involves the formation of a Schiff base through a reaction between the ketone and the aniline derivative in the first step, followed by a cycloalkenylation at the ortho-position to the amine functional group of the aniline derivative, and an annulation in the final step to close the quinoline ring, leading to a dihydroquinoline derivative. To the best of our knowledge, this is the first report of such a mechanistic pathway being proposed for any variant of the Skraup-Doebner-Von Miller quinoline synthesis.

A concise and scalable enantioselective total synthesis of the natural cardenolides cannogenol and cannogenol-3-O-α-L-rhamnoside has been achieved in 19 linear steps. The synthesis features a Cu(II)-catalyzed enantioselective and diastereoselective Michael reaction/tandem aldol cyclization and a one-pot reduction/transposition, which resulted in a rapid (6 linear steps) assembly of a functionalized intermediate containing C19 oxygenation that could be elabo-rated to cardenolide cannogenol. In addition, a strategy for achieving regio- and stereoselective glycosylation at the C3 position of synthetic cannogenol was developed and applied to the preparation of cannogenol-3-O-α-L-rhamnoside.