Generation Of Structural Diversity Research Articles

Generation of structural diversity in polyphosphazenes

Polyphosphazenes are macromolecules with a chain of alternating phosphorus and nitrogen atoms and with two (usually) organic side groups linked to each phosphorus. Although the earliest poly(organophosphazenes) were essentially linear polymers each bearing only one type of side group along the chain, research in our program in recent years has widened the scope to include mixed‐substituent polymers with two or more different side groups, block copolymers, comb structures, stars, and dendrimers, all with a wide variety of different properties. In addition, supramolecular systems have also been synthesized including vesicles, microspheres, and a variety of composite systems. This review provides a summary of these developments together with an introduction to the widening array of developing uses. Copyright © 2013 John Wiley & Sons, Ltd.

Insights into the Generation of Structural Diversity in a tRNA-Dependent Pathway for Highly Modified Bioactive Cyclic Dipeptides

The nocazines are a newly defined family of antibacterial and cytotoxic cyclic dipeptides produced by different actinobacterial species. Here, we identify a nocazine biosynthetic gene cluster in Nocardiopsis dassonvillei and describe the elucidation of the biosynthetic pathway leading to the nocazine family members nocazine E and XR334. Diketopiperazine (DKP) formation is carried out by a tRNA-dependent cyclodipeptide synthase (CDPS) showing an unknown product profile, while tailoring of the DKP-scaffold is achieved through the combined and combinatorialaction of a cyclodipeptide oxidase and two distinctSAM-dependent O-/N-methyltransferases. Our results help to illuminate the biosynthetic logic resulting in the structural diversity of the nocazine family and set the stage for exploring the biological function of modified cyclic dipeptides as possible mediators of host-pathogen and host-parasite interactions.

Synthesis and Biological Evaluation of a New Family of Constrained Azabicyclic Homocholine Analogues

A family of constrained acylated homocholine analogues have been synthesized, based on the azabicyclic ring scaffold derived from a double-Mannich annulation of cyclic ketones. The short synthetic route allows generation of structural diversity including, variation in the carbocyclic ring size, bridgehead substitution, nitrogen substitution and the ester sidechain. Biological assays on selected analogues demonstrate these compounds are nicotinic acetylcholine receptor (nAChR) antagonists. Several analogues also bind to other neuronal transporter and receptor targets.

Mutasynthesis of Geldanamycin by the Disruption of a Gene Producing Starter Unit: Generation of Structural Diversity at the Benzoquinone Ring

A not so familiar ring. We describe results obtained from a mutasynthetic study based on geldanamycin (1), and demonstrate that this technique can be used to extend the structural diversity of the benzoquinone ring of 1. Our results show that geldanamycin PKS modules tolerate polyketide intermediate chains that bear unnatural benzoate components, and that they extend these structures further to produce mature polyketides (see scheme). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2007/z700196_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.