Synthesis of the cardiotonic bemarinone, 5,6-dimethoxy-4-methyl-2(1H)-quinazolinone,utilizing a directed metalation approach

Several methods for the synthesis of bemarinone, 5,6-dimethoxy-4-methyl-2(1H)-quinazolinone, were explored with the most successful being a directed metalation route. Details of the lithiation and the subsequent reaction with electrophiles of 3′,4′-dimethoxy-2,2-dimethylpropioanilide and other derivatives of 3,4-dimethoxyaniline are given.     

A fractional version of the Erdős-Faber-Lovász conjecture

LetH be any hypergraph in which any two edges have at most one vertex in common. We prove that one can assign non-negative real weights to the matchings ofH summing to at most |V(H)|, such that for every edge the sum of the weights of the matchings containing it is at least 1. This is a fractional form of the Erds-Faber-Lovász conjecture, which in effect asserts that such weights exist and can be chosen 0,1-valued. We also prove a similar fractional version of a conjecture of Larman, and a common generalization of the two.Supported in part by NSF grant MCS 83-01867, AFOSR Grant 0271 and a Sloan Research Fellowship     

Hadwiger's conjecture forK 6-free graphs

In 1943, Hadwiger made the conjecture that every loopless graph not contractible to the complete graph ont+1 vertices ist-colourable. Whent3 this is easy, and whent=4, Wagner's theorem of 1937 shows the conjecture to be equivalent to the four-colour conjecture (the 4CC). However, whent5 it has remained open. Here we show that whent=5 it is also equivalent to the 4CC. More precisely, we show (without assuming the 4CC) that every minimal counterexample to Hadwiger's conjecture whent=5 is apex, that is, it consists of a planar graph with one additional vertex. Consequently, the 4CC implies Hadwiger's conjecture whent=5, because it implies that apex graphs are 5-colourable.Research partially supported by NSF grants number DMS 8903132, and DMS 9103480 respectively. Both authors were also partially supported by the DIMACS Center at Rutgers University, and the research was carried out partially under a consulting agreement with Bellcore.     

EVIDENCE FOR THE FORMATION OF A CHLOROPHYLL a/ZEAXANTHIN COMPLEX IN LECITHIN LIPOSOMES FROM FLUORESCENCE DECAY KINETICS

The interaction of Chi a with zeaxanthin (Zea), which is an analogue of lutein, has been studied in soya bean lecithin liposomes using the fluorescence of Chi as monitor. The fluorescence emission spectrum at 4.2 K of Chi a showed characteristic changes in the presence of Zea: the emission maximum shifted from 688 nm to 680 nm, and a peak at 731 nm appeared. The fluorescence decay kinetics of Chi a alone could be described by the sum of two exponential components (T₁,≅0.8 ns, T₂≅2.5 ns). In the presence of Zea a component with a long lifetime, T≅5 ns, appeared with a large relative amplitude (40%). This indicated the formation of a Chl a /Zea complex, in which Chl a /Chl a interaction is negligible, presumably because of strong interaction between Chl a and Zea. The fluorescence anisotropy decay kinetics supported the hypothesis of the formation of a large Chl a containing complex in the presence of Zea. A rotational correlation time, φ≅14 ns at 4°C and φ≅21 ns at 30°C, was found, which is distinctly larger than for samples containing Chl a only. We interpret these results as further evidence for a strong interaction between Chl a and Zea in the hydrophobic environment of the lecithin liposomes. This interaction may also occur in the Chl-proteins of the Chi alb light-harvesting complex of plant photosynthesis.     

Study of the metabolism of testosterone, nandrolone and estradiol in cattle.

The current metabolism study was undertaken to identify key analytes in urine, plasma and bile following testosterone, nandrolone and estradiol administrations to cull cows, heifers and steers. This information will be used to develop confirmatory analysis procedures. In the present study, mixtures (1:1) of testosterone, nandrolone or estradiol and their deuterium labelled analogues were administered to cull cows, heifers and steers. Two analogues of deuterium labelled testosterone were synthesised and administered, to facilitate identification of metabolites. Following administration, urine, plasma and bile samples were collected and subjected to solid phase extraction. The extracts were derivatised and analysed by GC-MS. The major analytes derived from the administered steroids were identified on the basis of the twin ion peaks produced for their non-labelled and deuterium labelled analogues and their stereochemistries determined by comparison of retention times with appropriate reference standards. Using suitable internal markers, excretion profiles for the major analytes in urine and plasma have been determined and levels in isolated bile samples estimated. This work is on-going, and this paper is a summary of some of the studies completed to date.     

Chiral recognition in solution and the gas phase. Experimental and theoretical studies of aromatic D- and L-amino acid-Cu(II)-chiragen complexes

This study was focused on distinguishing L- and D-enantiomers of amino acids using electrospray ionization mass spectrometry (ESI-MS) of ternary complexes with Cu(II) and chiral derivatives of bipyridine. A pinene-annulated derivative of 2,2'-bipyridine, (5R,7S,8S)-(--)-5,6,7,8-tetrahydro-6,6,8-trimethyl-2-(pyridin-2-yl)-5,7-methanoquinoline, called a chiragen, was used as the auxiliary ligand bound to Cu(II) to study the complexation of D- and L-phenylalanine and D- and L-tryptophan and their detection by MS. NMR studies showed that the D- and L-amino acid complexes can be distinguished in solution by the difference in the amount of band broadening of the alpha-carbon proton, with the D-complex showing greater broadening from a more intense interaction with the paramagnetic copper center. In ESI-MS studies, the ion abundances for the analyte complexes were compared with those of internal standards to investigate competition in binding to Cu(II)chiragen between the internal standard and D- and L-amino acids. The D-Phe complex showed stronger binding than the L-Phe complex, although differences in response related to solvent effects were also apparent. In studies involving two separate internal standards, the Trp enantiomers were practically indistinguishable in all but one solvent environment. In 100% methanol, the L-Phe and D-Phe complexes were readily distinguished and the L-Phe complex out-competed the L-Phe complex by a factor of two. Density functional theory calculations were performed on D- and L-complexes of Phe and Trp to determine the optimized geometries and the most energetically favorable structures. Calculations agreed with experiments, where the D-Phe complex was the most stable structure, while the L-Trp and D-Trp complexes were comparably stable in the gas phase.     

Acetylation of DMSO:PF solutions of cellulose

Three different techniques for esterifying solutions of cellulose dissolved in mixtures of dimethyl sulfoxide (DMSO) and paraformaldehyde (PF) were evaluated and are herein described. The evaluation and development of suitable synthetic procedures and the characteristics of the resulting acetylated cellulose are reported. Glacial acetic acid (glacial HOAc), acetyl chloride (AcCl), and acetic anhydride (Ac₂O) were compared as acetylating agents for solutions of cellulose in DMSO:PF, and it was demonstrated that mixtures of pyridine (Py) and Ac₂O rapidly acetylated the cellulose to yield beige to amber acetone-soluble cellulose acetates which were partially oxidized. These thermoplastic resins exhibited softening points between 80 and 110°C and thermal stabilities (in nitrogen atmospheres) similar to those of native celluloses (350 to 375°C). Degree of acetyl substitution (DS) values ranged from 0 to 2.0 as a function of acetylation time.     

Mass spectrometry of 1 phenyl-1, 2-dibromopropylphosphonic acid and its methyl ester

$\text{erythro}$-1-Phenyl-1,2-dibromopropylphosphonic acid is known to decompose rapidly into the monomeric metaphospbate-anion (PO₃), 1-phenyl-1-bromopropene, and bromide ion in protic or aprotic solvents in the presence of a hindered tertiary amine. The present study compares the behavior of this phosphonic acid in solution and in the gas phase. The gas-phase thermolysis of the acid involves mainly the loss of bromine and of the phosphoryl group, -P(O)(OR) (OR') (R = R' = H). The same type of pathway is followed in the ionization/excitation processes (“cationic reactions”) that follow from electron impact in mass spectrometry. The thermal and cationic reactions of the monomethyl and dimethyl esters of the phosphoric acids (R=H,R'= CH₃ and R = R' = CH₃, respectively, in -P(O)(OR)(OR')) are entirely analogous to those of the free dibasic acid.     

Preparation of block copolymers from occluded vinyl acetate macroradicals

Stable vinyl acetate macroradicals were produced by polymerization in a nonviscous poor solvent, a viscous good solvent and a viscous poor solvent. These macroradicals were then allowed to react with a second vinyl monomer to produce block copolymers. The formation of block copolymers was monitored for rate and yield data. The block copolymers produced were poly(vinyl acetate-b-methyl methacrylate), poly(vinyl acetate-b-acrylic acid), poly(vinyl acetate-b-vinylpyrrolidone), poly(vinyl acetate-b-acrylonitrile), poly(vinyl acetate-b-styrene), and poly(vinyl acetate-b-methyl acrylate). The block copolymers were characterized by yield, precipitation in selected solvents, pyrolysis gas chromatography, and differential scanning calorimetry.     

The Solutions of a Model Nonlinear Singular Perturbation Problem Having A Continuous Locus of Singular Points

Consider the boundary value problem εy″ =(y² ? t²)y′, ?1 ?t?0, y(?1) = A, y(0) = B. We discuss the multiplicity of solutions and their limiting behavior as ε→+0+ for certain choices of A and B. In particular, when A = 1, B = 0, a bifurcation analysis gives a detailed and fairly complete analysis. The interest here arises from the complexity of the set of "turning points."