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.     

On the interpretation of fluorescence anisotropy decays from probe molecules in lipid vesicle systems

Measurements of fluorescence depolarization decays are widely used to obtain information about the molecular order and rotational dynamics of fluorescent probe molecules in membrane systems. This information is obtained by least-squares fits of the experimental data to the predictions of physical models for motion. Here we present a critical review of the ways and means of the data analysis and address the question how and why totally different models such as Brownian rotational diffusion and wobble-in-cone provide such convincing fits to the fluorescence anistropy decay curves. We show that while these models are useful for investigating the general trends in the behavior of the probe molecules, they fail to describe the underlying motional processes. We propose to remedy this situation with a model in which the probe molecules undergo fast, though restricted local motions within a slowly rotating cage in the lipid bilayer structure. The cage may be envisaged as a free volume cavity between the lipid molecules, so that its position and orientation change with the internal conformational motions of the lipid chains. This approach may be considered to be a synthesis of the wobble-in-cone and Brownian rotational diffusion models. Importantly, this compound motion model appears to provide a consistent picture of fluorescent probe behavior in both oriented lipid bilayers and lipid vesicle systems.     

Der Richtungsabstand

In the study of chemical structural phenomena, the idea of mixedness appears to provide most valuable information if this notion is understood as a quantity that counts for a natural distinction between more or less mixed situations. The search for such a concept was initiated by the need of a corresponding valuation of chemical molecules that differ in the type-composition of a system of varying molecular parts at given molecular skeleton sites. In other words, an order relation for the partitions of a finite set was sought that explains the extent of mixing in a canonical way. This and related questions led to the concepts of themixing character andmixing distance. Success in applying these concepts to further chemical and physical problems, to graph theory, to representation theory of the symmetric group, and to probability theory confirmed the hope that there is a common background in some basic mathematics that allows a systematic treatment.The expected concept summarizing the above-mentioned experience is called thedirection distance and the mathematics concerned is linear geometry with a normspecific metric or structural analysis of normed vector spaces, respectively. Direction distance is defined as a map that represents the total metric information on any pair of directions (= pair of half-lines with a common vertex or a corresponding figure in normed vector spaces). Generally, that metrical figure changes when the half-lines are interchanged. As a consequence thereof, Hilbert's congruence axioms do not permit a metric criterion for the congruence of angles except in particular cases. The metric figures of direction pairs, however, may be classified according to metric congruence, and the normspecific metric induces an order in the set of congruence classes. This order, as a rule, is partial; it proves to be total if and only if the vector spaces are (pre-) Hilbert spaces (Lemma 8). A thorough comparison of the direction distance with the conventional distance deepens the understanding of the novel concept and justifies the terminology. The results are summarized in a number of lemmata. Furthermore, so-calledd-complete systems of order-homomorphic functional (so-calledd-functionals) establish an alternative formulation of the direction distance order. If and only if the order is total,d-complete systems can be represented by singled-functionals. Consequently, the case that normed vector spaces are (pre-) Hilbert spaces is pinpointed by the fact that the negative scalar product is already ad-complete system. These particular circumstances allow a metric congruence relation for angles.Another family of normed vector spaces is traced out by the conditions under which the direction distance takes the part of the mixing distance. Roughly speaking, a subset of vectors may be viewed as representing mixtures if it has two properties. First, with any two vectors of this subset all positive linear combinations are vectors of it as well. Second, the length of these vectors is an additive property. Correspondingly, the definition of the mentioned family, the family of so-calledmc-spaces, is based on the concepts of ameasure cone (Def. 5 and Def. 5) and an associated class ofmc- (= measure cone)norms being responsible for length additivity ofpositive vectors (= vectors of the measure cone) (Def. 6). Such norms provide congruence classes for positive vectors and positive direction pairs marked by the propertieslength andmixing distance, respectively. These congruence classes do not depend on the choice of the particularmc-norm within the class associated with a given measure cone, however, the mixing distance does. The consistency of the stipulated mathematical instrumentarium becomes apparent with Theorem 1 stating: The mixing distanceorder doesnot depend on the choice of a particular norm within the measure cone specific class; this order, together with the stipulated length of positive vectors, are properties necessary and sufficient for fixing the measure cone specific class ofmc-norms.Decreasing (or constant) mixing distance was found to describe a characteristic change in the relation between two probability distributions on a given set of classical events, a change in fact necessary and sufficient for the existence of alinear stochastic operator that maps a given pair of distributions into another given pair. This physically notable statement was originally proved for the space ofL ¹-functions on a compact -interval, it was expected to keep its validity for probability distributions in the range of classical physics and, as a consequence of that, for measures of any type. Theorem 2 presents the said statement in terms ofmc-endomorphisms ofmc-spaces; after an extension of the original proof to a more general family ofL ¹-spaces another method presented in a separate paper confirms Theorem 2 for bounded additive set functions and, accordingly, secures the expected range of validity. The discussion below is without reference to the validity range and primarily devoted to geometrical consequences without detailed speculations about physical applications.A few remarks on applications, however, illustrate the physical relevance of the mixing distance and its specialization, theq-character, in the particular context of Theorem 2. With reference to measure cones with such physical interpretations as statistical systems,mc-endomorphisms effect changes that can be described by linear stochastic operators and result physically either from an approach to some equilibrium state or from an adoption to a time-dependent influence on the system from outside. Theorem 2 provides a necessary and sufficient criterion for such changes. The discussion may concern phenomena of irreversible thermodynamics as well as evolving systems under the influence of a surrounding world summarized asorganization phenomena. Entropies and relative entropies of the Renyi-type ared-functionais which do not establishd-complete systems. The validity of Theorem 2 does not encompass the nonclassical case; the reason for it is of high physical interest. The full range of validity and its connection with symmetry arguments seems a promising mathematical problem in the sense of Klein'sErlanger Programm. From the point of mathematical history, the Hardy-Littlewood-Polya theorem should be quoted as a very special case of Theorem 2.

     

A bound for minimal graphs with a normal at infinity

It is shown that a minimal graph with a normal at infinity is in a-priori bounded vertical distance from its approximating halfcatenoid. This is used to show that the exterior contact angle problem is wellposed under natural geometric conditions on the domain, while the exterior Dirichlet problem can be solvable only for data which satisfy an oscillation bound.This paper was written under the support of the Deutsche Forschungsgemeinschaft while the author was visiting the department of mathematics at Stanford University.This article was processed by the author using the LaT_EX style filepljour1 from Springer-Verlag.     

Diffusion in Lorentz lattice gas automata with backscattering

The probability of first return to the initial intervalx and the diffusion tensorD _x are calculated exactly for a ballistic Lorentz gas on a Bethe lattice or Cayley tree. It consists of a moving particle and a fixed array of scatterers, located at the nodes, and the lengths of the intervals between scatterers are determined by a geometric distribution. The same values forx andD _x apply also to a regular space lattice with a fraction of sites occupied by a scatterer in the limit of a small concentration of scatterers. If backscattering occurs, the results are very different from the Boltzmann approximation. The theory is applied to different types of lattices and different types of scatterers having rotational or mirror symmetries.