Enantioselective synthesis of diversely substituted quaternary 1,4-benzodiazepin-2-ones and 1,4-benzodiazepine-2,5-diones

Benzodiazepines are privileged scaffolds in medicinal chemistry, but enantiopure examples containing quaternary stereogenic centers are extremely rare. We demonstrate that installation of the di(p-anisyl)methyl (DAM) group at N1 of 1,4-benzodiazepin-2-ones and 1,4-benzodiazepine-2,5-diones derived from enantiopure proteinogenic amino acids allows retentive replacement of the C3-proton via a deprotonation/trapping protocol. A wide variety of carbon and nitrogen electrophiles function well in this reaction, providing the corresponding quaternary benzodiazepines with excellent enantioselectivity. Deprotonation/trapping experiments on a pair of diastereomeric 1,4-benzodiazepine-2,5-diones provide evidence for a key role of conformational chirality in these enantioselective reactions. Acidic removal of the DAM group is fast and high-yielding and can be performed selectively in the presence of a N-Boc indole. Thus the synthesis of quaternary benzodiazepines with diverse N1 functionality can now be accomplished.     

Nanosized polymetallic resorcinarene-based host assemblies that strongly bind fullerenes

Polymetallic nanodimensional assemblies have been prepared via metal directed assembly of dithiocarbamate functionalized cavitand structural frameworks with late transition metals (Ni, Pd, Cu, Au, Zn, and Cd). The coordination geometry about the metal centers is shown to dictate the architecture adopted. X-ray crystallographic studies confirm that square planar coordination geometries result in "cagelike" octanuclear complexes, whereas square-based pyramidal metal geometries favor hexanuclear "molecular loop" structures. Both classes of complex are sterically and electronically complementary to the fullerenes (C(60) and C(70)). The strong binding of these guests occurred via favorable interactions with the sulfur atoms of multiple dithiocarbamate moieties of the hosts. In the case of the tetrameric copper(II) complexes, the lability of the copper(II)-dithiocarbamate bond enabled the fullerene guests to be encapsulated in the electron-rich cavity of the host, over time. The examination of the binding of fullerenes has been undertaken using spectroscopic and electrochemical methods, electrospray mass spectrometry, and molecular modeling.     

Dynamical forcing of circular groups

In this paper we introduce and study the notion of dynamical forcing. Basically, we develop a toolkit of techniques to produce finitely presented groups which can only act on the circle with certain prescribed dynamical properties.

As an application, we show that the set consisting of rotation numbers which can be forced by finitely presented groups is an infinitely generated -module, containing countably infinitely many algebraically independent transcendental numbers. Here a rotation number is forced by a pair , where is a finitely presented group and is some element, if the set of rotation numbers of as varies over is precisely the set .

We show that the set of subsets of which are of the form

where varies over countable groups, are exactly the set of closed subsets which contain and are invariant under . Moreover, we show that every such subset can be approximated from above by for finitely presented .

As another application, we construct a finitely generated group which acts faithfully on the circle, but which does not admit any faithful action, thus answering in the negative a question of John Franks.

     

Promoting essential laminations

We show that a co-orientable taut foliation of a closed, orientable, algebraically atoroidal 3-manifold is either the weak stable foliation of an Anosov flow, or else there are a pair of very full genuine laminations transverse to the foliation.     

The admissibility of M11 over number fields

A group G is $\mathbb{Q}$-admissible if there exists a G-crossed product division algebra over $\mathbb{Q}$. The $\mathbb{Q}$-admissibility conjecture asserts that every group with metacyclic Sylow subgroups is $\mathbb{Q}$-admissible. We prove that the Mathieu group $M_{11}$ is $\mathbb{Q}$-admissible, in contrast to any other sporadic group.     

High-resolution STM imaging of novel poly(G)-poly(C) DNA molecules

High-resolution scanning tunneling microscopy (STM) imaging of single double-stranded poly(G)-poly(C) DNA molecules, made by a novel synthesis method, shows the molecules morphology. The STM images reveal a periodic structure of approximately 4 nm, seen as repeating "bulbs" along the molecules. These "bulbs" are associated with the molecule helix (the major grooves). "Nicks", two per 100 nm on the average, are observed along the DNA as well. The STM measurements were supported by a morphological statistics of the DNA molecule groove length and apparent height relative to the surface.     

A Characterization of the degree sequences of 2‐trees

A graph G is a 2‐tree if G = K₃, or G has a vertex v of degree 2, whose neighbors are adjacent, and G/ v is a 2‐ tree. A characterization of the degree sequences of 2‐trees is given. This characterization yields a linear‐time algorithm for recognizing and realizing degree sequences of 2‐trees. © 2008 Wiley Periodicals, Inc. J Graph Theory 58:191‐209, 2008     

Synthesis of the 7-deaza and 5-aza-7-deaza purine analogs of the antiherpes agent 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG)

Synthesis of 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3-d]pyrimidin-4-one (3) a 7-deaza purine analogue and 2-amino-8-[(1,3-dihydroxy-2-propoxy)methyl]imidazo[1,2-a]-s-triazin-4-one (4) a 5-aza-7-deaza purine analogue of DHPG (2) are reported.     

Immunofiltration as sample cleanup for the immunochemical detection of beta-agonists in urine

Despite the ban of the European Union on use of drugs to improve animal growth, occasionally beta-agonist drugs are still found in samples from cattle. Over time, the specified limits for the detection of these illegal drugs have been lowered. To improve the immunochemical screening of urine samples to detect lower levels of several beta-agonists, immunofiltration (IF) was applied for sample cleanup in combination with a beta-agonist-ELISA. In the applied IF format, free (non-immobilised) anti-salbutamol polyclonal antibodies were mixed with the urine sample in an ultra-filtration device (cut off 30 kDa) and the sample was removed by centrifugation. The antibody bound beta-agonists were freed from the antibodies by the addition of a mixture of methanol and 0.1 M acetic acid (1:1; v/v) and centrifugation. The filtrate, containing the free beta-agonists, was evaporated to dryness and the residue dissolved in buffer, an aliquot of which was analysed with the beta-agonist ELISA. Compared with the direct beta-agonist ELISA, this IF cleanup procedure resulted in a 30-times lower limit of detection (LOD) of 0.14 ng ml(-1) (salbutamol equivalents). The anti-salbutamol antibodies recognised several beta-agonists and the combination of IF with the beta-agonist ELISA was found suitable for the detection of at least ten beta-agonists in urine with comparable LODs.