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Furo[3,4-b]benzodioxin 1 was found to undergo a doubleDiels–Alder reaction with several dienophiles. The diene reacts directly with the suitable dienophile to give the mono-adduct intermediate that unexpectedly leads to a second cycloaddition at the internal, electron-rich, oxabicyclic C4a–C10a double bond. The resulting bis-adducts were formed under relatively mild conditions with dienophiles ranging from maleic anhydride and dimethyl acetylenedicarboxylate to the extremely reactive arynes. With this methodology of two uninterrupted sequential cycloaddition reactions, interesting formation of stable bis-adducts was observed. The dienophile behavior of 1,4-benzodioxin is described for the first time in this work.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A set of disubstituted tetracyclic lactones has been synthesized and tested for potential antitumor activity. Several of them possess a noticeable cytotoxicity against L1210 and HT-29 colon cells in vitro. Relationships between chain nature and biological properties were sought. Lactones with a pentyl or hexyl substituent at C-11 are the most active ones. The introduction of a functional group at the side chain of C-11 modified the potency; carboxylic acid and primary amine decreased the cytotoxicity, whereas a cyano group increased the activity. An extensive structure-activity relationship study of these derivatives, including carbon homologues and bioisosteres has been performed. The synthesis and cytotoxicity of these compounds are discussed. Two lactones are recognized as potential lead compounds.

Aryl halides and aryl triflates (triflate = trifluoromethanesulfonyl) are coupled with N-compounds to give the corresponding arylamines or arylhydrazines in the presence of a palladium catalyst, a suitable ligand, and a base. Catalyst systems consisting of palladium (II) and BINAP or triphenylphos phine are generally effective for the amination of a wide range of aryl halides and aryl triflates with anilines and hydrazines.

Electron density protein alignments are analyzed in terms of their underlying similarity measure, the density overlap. These alignments are conceptually unrelated to biochemical structural elements and, therefore, are appropriate in structure-only similarity studies. The analysis is focused on the low sequence similarity subset of protein domains. A remarkable association is found between simple, density overlap measures and the expert designed Structural Classification of Proteins (SCOP) for which functional and evolutive analogies prevail. The association found validates the functional significance of electron density alignments.

We describe the implementation of the spin-unrestricted Laplace transform fourth-order perturbative triples correction. A reduction in the computational scaling with respect to canonical implementations is attained without relying on the large molecule asymptote. The intrinsic scaling difficulties that the Laplace equations exhibit upon increasing the size of the basis sets are properly addressed. The method is suited for medium-size molecules.

A reformulation of the perturbative triples correction to coupled cluster singles and doubles (CCSD) based on the numerical Laplace transform of the energy denominator is presented. Rearranged equations reduce the O(N7) canonical scaling to O(N6), where N is a size measure of the electronic system. Two to three quadrature points is adequate for chemical predictions. The Laplace ansatz permits simple, noniterative expressions in noncanonical orbital representations. Furthermore, substituting canonical by generalized CCSD natural orbitals, the Laplace ansatz exhibits scaling close to O(N5), while retaining accuracy and providing crossover with respect to canonical triples for small size systems. A developing atomic orbital formulation is also introduced.

Using the Hartree–Fock and MP2 methods with bases of up to 6-31++G(2d, 2p) quality, the optimum geometry of the 1:2 and 2:1 (H2O)n… (HF)m complexes of water and hydrogen fluoride is searched in a systematic way. Two minimum-energy conformations are found for the 1:2 complex connected through a low-energy transition state. For the 2:1 complex, only one minimum-energy structure is obtained. The analysis of the geometries of the minima and their vibrational frequencies shows that none of them can be used to explain the existence of the H …FH reverse complex detected experimentally. © 1994 John Wiley & Sons, Inc.

Several nonparametric regressors have been applied to modeling quantitative structure−activity relationship (QSAR) data. The simplest regressor, the Nadaraya−Watson, was assessed in a genuine multi...

Aryl bromides are coupled with N -compounds to give the corresponding arylamines in the presence of a palladium catalyst, a suitable ligand, and a weak base. The catalysts perform well for a large number of different starting material combinations at 100–150 °C with drops of toluene or without solvent, and with low catalyst levels (0.12 mol % Pd). The low catalyst amount makes the process environment friendly.

A new algorithm for quantitative assessment of similarity between two atoms in molecules is presented. Both the atomic similarity index and its derivatives with respect to the three Euler angles that describe the mutual orientation of the atoms under comparison are computed efficiently by taking advantage of the recently developed analytical representations for atomic zero-flux surfaces. The use of such representations makes it possible to substantially enhance the accuracy of the computed similarity indices without increasing the cost of their evaluation. Numerical tests involving oxygen atoms in several carbonyl compounds demonstrate the ability of the new algorithm to discern small changes in atomic similarity that are brought about by second-neighbor effects. Comparisons among hydrogen atoms in the acrolein molecule reveal the usefulness of the similarity index in detection and quantification of the effects of steric interactions on atomic shapes. © 1996 by John Wiley & Sons, Inc.

A quantum similarity measure between two molecules is normally identified with the maximum value of the overlap of the corresponding molecular electron densities. The electron density overlap is a function of the mutual positioning of the compared molecules, requiring the measurement of similarity, a solution of a multiple-maxima problem. Collapsing the molecular electron densities into the nuclei provides the essential information toward a global maximization of the overlap similarity function, the maximization of which, in this limit case, appears to be related to the so-called assignment problem. Three levels of approach are then proposed for a global search scanning of the similarity function. In addition, atom)atom similarity Lorentzian potential functions are defined for a rapid completion of the function scanning. Performance is tested among these three levels of simplification and the Monte Carlo and simplex methods. Results reveal the present algorithms as accurate, rapid, and unbiased techniques for density-based molecular alignments. Q 1997 by John Wiley & Sons, Inc. J Comput Chem 18: 826)846, 1997