Highly Efficient and Practical Syntheses of Lavendamycin Methyl Ester and Related Novel Quinolindiones

The novel 7-(N-formyl-, 7-(N-acetyl-, and 7-(N-isobutyrylamino)-2-methylquinoline-5,8-diones were synthesized in excellent overall yields in three steps via the nitration of the commercially available 8-hydroxy-2-methylquinoline followed by a reduction-acylation step and then oxidation. Acid hydrolysis of 7-(N-acetylamino)-2-methylquinoline-5,8-dione (14a) afforded the novel 7-aminoquinoline-5,8-dione 7 in excellent yields. Due to our efficient preparation of dione 14a, we now report a short and practical method for the total synthesis of the potent antitumor agent lavendamycin methyl ester (1b) with an excellent overall yield.     

Application of the shape group method to conformational processes: Shape and conjugation changes in the conformers of 2-phenyl pyrimidine

The shape group method (SGM) and the associated (a,b)-parameter maps provide a detailed shape characterization of molecular charge distributions. This method is applied to the study of the variations of shape and conjugation of conformers of 2-phenyl pyrimidine in their electronic ground state. Within the SGM framework, the method of (a,b)-parameter maps provides a concise, nonvisual, algorithmic technique for shape characterization of molecules with fixed nuclear geometries. Moreover, shape codes derived from the (a,b)-parameter maps afford a practical means for efficiently storing the shape properties of molecules in an electronic database. The shape codes of two or more charge distributions can be compared directly, and numerical measures of molecular shape similarity can be computed using a technique that is simple, fast, and inexpensive, especially in relation to direct, pairwise comparisons of electronic charge densities. The quantitative and automated nature of the method suggests applications in the field of computer-aided molecular design. In this study, the method is used for the first time to determine detailed numerical shape codes and shape similarity measures for a nontrivial conformational problem involving changes in energy and in conjugation. Numerical shape similarity measures of eight conformers of 2-phenyl pyrimidine are determined and correlated with variations in conformational energy and conjugation. The competing effects of steric repulsion and conjugation lead to important correlations between conformational energy and shape. © 1995 John Wiley & Sons, Inc.     

Magnetic exchange interactions in tetrabromocuprate compounds

Magnetic and structural data for 28 compounds containing the tetrabromocuprate ion are presented. The parameters which affect the strength and sign of the magnetic superexchange interaction via non-bonding contacts between bromide ions are described and a system for describing the topology of the interaction between tetrahedra is proposed. Analysis of the data suggests that the primary factors affecting the magnetic exchange are the Br?Br distance, the Cu-Br?Br angle and the Cu-Br?Br-Cu dihedral angle.     

Chiral environments for asymmetric hydrogenation of model didehydro-amino acid residues

Dedicated to Professor John C. Sheehan on the occasion of his sixty-fifth birthday Nmr and glc analysis of diastereoisomeric mixtures of dipeptides has been used to study the asymmetric hydrogenation of model benzoyldidehydro- and trifluoroacetyldidehydro-dipeptide methyl esters. Chiral enhancement of one isomeric form appears to be independent of the N-terminal acyl group, but is significantly influenced by the choice of amino-acid in the C-terminal position. C-Terminal aromatic amino-acids and their derivatives give the best chiral enhancement during hydrogenation of a neighbouring dehydroamino-acid residue.     

A total synthesis of tarchonanthuslactone exploiting N-pyrrole carbinols as efficient stereocontrolling elements

[reaction: see text] A short stereoselective total synthesis of the polyketide natural product, tarchonanthuslactone, has been achieved. The key sequence involves the first reported catalytic enantioselective reduction of an N-acyl pyrrole and subsequent use of this stereocenter in a diastereoselective reductive cascade. This proceeded with unprecedentedly high stereocontrol and offered an elegant method of generating the desired syn stereochemistry present in the final target in one step.     

Determination of post-translational modifications of proteins by high-sensitivity, high-resolution Fourier transform ion cyclotron resonance mass spectrometry

The response of a cell to its extracellular environment is a multi-step process beginning with signal transduction that is governed by "subtle changes" often resulting in protein expression. Proteomics is the tracking of this protein expression. Post-translational modification (PTM) is a "subtle change" that has a major influence on signal transduction. Phosphorylation and glycosylation propagate signals by sequential, reversible modifications. High-sensitivity, high-resolution and multiple MS capabilities of Fourier transform ion cyclotron resonance mass spectrometry permit localization of the PTM(s) with electron-capture dissociation, and then structural determination of the PTM with infrared multiphoton dissociation.     

Dynamic behavior of potentiometric ammonia-sensing probes in samples of high osmolarity

Results are presented for potentiometric ammonia gas-sensors which show that the response times increase significantly with age of the sensor when ammonium picrate is used as internal electrolyte and the samples have greater osmolarities than the internal electrolyte solution. A build-up of ammonium picrate crystals on the inner side of the gas-permeable membrane is responsible for this increasein response time. The use of ammonium chloride as internal electrolyte provides constant response times indepent of sample osmotic strength, and is recommended as a means of ensuring that optimal dynamic response characteristics are maintained.     

On the role of solvent in complexation equilibria. I. The acid-base chemistry of some α,ω-diaminocarboxylic acids in water-dioxane mixed solvents

The macroscopic and microscopic acid-base chemistry of a series of α,ω-diaminocarboxylic acids, H₂N(CH₂)_nCH(NH₂)COOH [n=4, lysine (LYS);n=3, ornithine (ORN);n=2, 2,4-diaminobutyric acid (DAB);n=1, 2,3-diaminopropionic acid (DAP)], was determined in water and its binary mixtures with dioxane (20.5, 40.7, 60.7, and 80.5 mass % dioxane) using carbon-13 nuclear magnetic resonance spectroscopy. The macroscopic acid dissociation constants for the titration of the two ammonium groups decrease uniformly with increasing dioxane composition. The microscopic constants, however, which characterize the relative concentrations of the two tautomers of singly protonated amino acid (I and II) $$\begin{gathered} H_3 \mathop N\limits^ + (CH_2 )_n CHCOO^ - H_2 N(CH_2 )_n CHCOO^ - \hfill \\ || \hfill \\ NH_2 \mathop N\limits_ + H_3 \hfill \\ III \hfill \\ \end{gathered}$$ reveal that while tautomer I is favored in aqueous solution, tautomer II becomes more important with increasing dioxane composition for LYS and ORN. The relative concentrations of I and II remain unchanged with solvent composition for DAP. These results are explained in terms solute-solvent and solvent-solvent interactions.