Synthesis of anthracyclines via a claisen-diels-alder sequence

Naphthalene 16, a key intermediate for the synthesis of nogalamycin, was prepared in a six step sequence in 25% overall yield. The key step was a tandem Claisen-Diels-Alder sequence wherein the B- and C-rings were introduced in a single step. The naphthalene subunit was introduced by selenenylation of a β-diketone.     

Spectroscopic, kinetic, and mechanistic study of a new mode of coordination of indole derivatives to platinum(II) and palladium(II) ions in complexes

Binding of tryptophan residue to intrinsic metal ions in proteins is unknown, and very little is known about the coordinating abilities of indole. Indole-3-acetamide displaces the solvent ligands from cis-[Pt(en)(sol)2]2+, in which sol is acetone or H2O, in acetone solution and forms the complex cis-[Pt(en)(indole-3-acetamide)]2+ (3) of spiro structure, in which the new bidentate ligand coordinates to the Pt(II) atom via the C(3) atom of the indolyl group and the amide oxygen atom. This structure is supported by 1H, 13C, 15N, and 195Pt NMR spectra and by UV, IR, and mass spectra. Molecular mechanical simulations by Hyperchem and CHARMM methods give consistent structural models; the latter is optimized by density-functional quantum chemical calculations. Dipeptide-like molecules N-(3-indolylacetyl)-L-amino acid in which amino acid is alanine, leucine, isoleucine, valine, aspartic acid, or phenylalanine also displace the solvent ligands in acetone solution and form complexes cis-[Pt(en) N-(3-indolylacetyl)-L-amino acid)]2+ (6), which structurally resemble 3 but exist as two diastereomers, detected by 1H NMR spectroscopy. The bulkier the amino acid moiety, the slower the coordination of these dipeptide-like ligands to the Pt(II) atom. The indolyl group does not coordinate as a unidentate ligand; a second donor atom is necessary for bidentate coordination of this atom and the indolyl C(3) atom. The solvent-displacement reaction is of first and zeroth orders with respect to indole-3-acetamide and cis-[Pt(en)(sol)2]2+, respectively. A mechanism consisting of initial unidentate coordination of the ligand via the amide oxygen atom followed by closing of the spiro ring is supported by 1H NMR data, the kinetic effects of acid and water, and the activation parameters for the displacement reaction. In the case of N-(3-indolylacetyl)-L-phenylalanine, the bulkiest of the entering ligands, the reaction is of first order with respect to both reactants. The bidentate indole-3-acetamide ligand in 3 is readily displaced by (CH3)2SO and 2-methylimidazole, but not by CNO-, CH3COO-, and CH3CN. Complexes cis-[Pd(en)(sol)2]2+ and cis-[Pd(dtco)(sol)2]2+ react with indole-3-acetamide more rapidly than their Pt(II) analogues do and yield complexes similar to 3. This study augments our recent discovery of selective, hydrolytic cleavage of tryptophan-containing peptides by Pd(II) and Pt(II) complexes.     

Efficient calculation of spectral density functions for specific classes of singular Sturm–Liouville problems

New families of approximations to Sturm–Liouville spectral density functions are derived for cases where the potential function has one of several specific forms. This particular form dictates the type of expansion functions used in the approximation. Error bounds for the residuals are established for each case. In the case of power potentials the approximate solutions of an associated terminal value problem at ∞$\infty$ are shown to be asymptotic power series expansions of the exact solution. Numerical algorithms have been implemented and several examples are given, demonstrating the utility of the approach.     

New characterizations of spectral density functions for singular Sturm–Liouville problems

A generalization is given for a characterization of the spectral density function of Weyl and Titchmarsh for a singular Sturm–Liouville problem having absolutely continuous spectrum in [0,∞)$[0,\infty )$. A recurrent formulation is derived that generates a family of approximations based on this scheme. Proofs of convergence for these new approximations are supplied and a numerical method is implemented. The computational results show more rapid rates of convergence which are in accord with the theoretical rates.