One-Step Assembly of Functionalized Morpholinones and 1,4-Oxazepane-3-ones via [3 + 3]- And [3 + 4]-Annulation of Aza-Oxyallyl Cation and Amphoteric Compounds

A new [3 + 3]- and [3 + 4]-annulation strategy involving azaoxyallyl cation and [1,m]-amphoteric compounds (m = 3,4) is presented. This concise method enables easy assembly of functionalized saturated N-heterocycles, comprised of six-and seven-membered rings and is of high significance in the context of drug discovery approaches. This reaction also represents a new trapping modality of the azaoxyallyl cation with amphoteric agents of different chain lengths that consist of a heteroatom nucleophilic site and a π-electrophilic site

Design And Synthesis of Ring-Expanded Analogues of Amino Sugars And Discovery of A Phosphine Catalyzed Tandem Cycloisomerization And [4+2] Cycloaddition Reaction Sequence

The preparation of 2-amino septanosides has been accomplished in two different processes. One route utilized a p-toluenesulfonic acid mediated cyclization of 1,6-hydroxyaldehydes at room temperature. Excess alcohol was necessary in this process for the formation of septanosyl glycosides. The other route used septanosyl fluorides, themselves prepared from the same 1,6-hydroxyaldehydes, as glycosyl donors in the presence of a variety of acceptors. This method provided more general and efficient access to different 2-amino septanosides. Based on the unique reactivities observed during intramolecular reactions of the septanosyl fluorides, we postulated that the transformation to septanosides for each process followed a different mechanistic pathway. Activation of septanosyl fluorides likely formed a cyclic oxocarbenium ion intermediate that then reacted with the acceptor to produce the corresponding glycosides; this is akin to reactions observed for pyranoses. In the case of hydroxyaldehyde cyclization and glycosylation, an acyclic oxocarbenium pathway was likely dominant. Glycosylations involving the septanosyl fluorides gave good reaction yields and high selectivity for formation of α-septanoside linkages. Both of the methods developed could serve as a starting point for more elaborate investigations with septanose-based glycoconjugates. ^ In a separate project, a phosphine catalyzed tandem process has been developed. Over the course of the tandem reaction. hemiketals (masked ynones) isomerize to cyclic keto enol ethers in the presence of a phosphine. The cyclic keto enol ethers serve as important building blocks and are amenable for functionalization either at the enol ether moiety or the keto group. Depending upon the nature of the alkyne-moiety present in original hemiketal, differential reactivity was observed for the formation of cyclic keto enol ether products. Hemiketals with a terminal alkyne gave the corresponding enone product, which was not isolable. It underwent a rapid dimerization that led to dimeric spiroketal products. Data collected in this study suggested that the dimerization occurs via a concerted hetero Diels-Alder process. In cases where a phenyl group was on the β carbon the cyclic keto enol ether, the product was stable and isolable. The utility of the methodology was further demonstrated by an one pot transformation of phenyl-substituted hemiketals to functionalized dihydropyrazoles. Overall, the tandem method allows for the rapid introduction of complexity in the products from relatively simple starting materials.

Institutional Imperfections and Buyer-Induced Holdout in Land Acquisition

We look beyond the well-studied issues of fair compensation, regulatory takings, and seller-induced holdout that arise in the government purchase of land for economic development. We argue that political rivalry distorts land acquisition negotiations between private sellers and a private buyer driven by profits.We determine these distortions endogenously and characterise conditions when the buyer’s optimal design to acquire land generates holdout. We analyse how bureaucratic corruption that increases transaction costs affects the degree and direction of political distortions and the incidence of holdout. We find that the size of corruption has nuanced nonmonotonic influences on holdout, seller welfare, and buyer’s profits

Lewis acid catalyzed annulation of spirocyclic donor-acceptor cyclopropanes with exo-heterocyclic olefins: Access to highly functionalized bis-spirocyclopentane oxindole frameworks

Lewis acid catalyzed highly efficient [3+2] annulation of spirocyclic Donor-Acceptor cyclopropanes (DACs) with exo-heterocyclic olefins is reported to furnish various biologically relevant dispiro-2,3-dioxopyrrolidine[cyclopentane]oxindole and dispiropyrazolone[cyclopentane]oxindole frameworks. This report highlights the use of oxindole-activated spiro-DACs as potential synthons to access complex dispirocarbocyclic oxindoles via ring-enlargement of the former, with high yields and diastereoselectivity

Hypoxia-Activated Small Molecule-Induced Gene Expression

Hypoxia, conditions of reduced oxygen, occur in a wide variety of biological contexts, including solid tumours and bacterial biofilms, which are relevant to human health. Consequently, the development of chemical tools to study hypoxia is vital. Here we report a hypoxia-activated small molecule-mediated gene expression system using a bioreductive prodrug of the inducer isopropyl 1-thio-β-D-galactopyranoside (IPTG). As a proof-of-concept we have placed the production of a green fluorescent protein under the control of hypoxia. Our system has the potential to be extended to regulate the production any given protein of choice.</div

Institutional imperfections and buyer-induced holdout in land acquisition

We look beyond the well-studied issues of fair compensation, regulatory tak-ings, and seller-induced holdout that arise in the government purchase of land for economic development. We argue that political rivalry distorts land acquisition negotiations between private sellers and a private buyer driven by profits. We determine these distortions endogenously and characterise conditions when the buyer’s optimal design to acquire land generates holdout. We analyse how bureaucratic corruption that increases transaction costs affects the degree and di-rection of political distortions and the incidence of holdout. We find that the size of corruption has nuanced nonmonotonic influences on holdout, seller welfare, and buyer’s profits

Discovery of a Phosphine-Mediated Cycloisomerization of Alkynyl Hemiketals: Access to Spiroketals and Dihydropyrazoles via Tandem Reactions

Reported here are details on the discovery of a phosphine-catalyzed isomerization of hemiketals and subsequent reactions of the cyclic keto enol ether products. The new cycloisomerization complements a previously reported amine-catalyzed process that gave oxepinones from the same hemiketal starting materials. In the absence of functionality (R²) on the cyclic keto enol ether, a rapid and facile dimerization occurs, giving spiroketal products. When the enone is substituted (i.e., R² = Ph), the cyclic keto enol ether is sufficiently stable so that it can be isolated; it can then be further reacted in the same pot to provide the corresponding dihydropyrazoles. Both the spiroketal and dihydropyrazole products arise by a tandem reaction that begins with the novel cycloisomerization. The method allows for the rapid introduction of complexity in the products from relatively simple starting materials. It should find application in the synthesis of natural product-like molecules

Discovery of a Phosphine-Mediated Cycloisomerization of Alkynyl Hemiketals: Access to Spiroketals and Dihydropyrazoles via Tandem Reactions

Reported here are details on the discovery of a phosphine-catalyzed isomerization of hemiketals and subsequent reactions of the cyclic keto enol ether products. The new cycloisomerization complements a previously reported amine-catalyzed process that gave oxepinones from the same hemiketal starting materials. In the absence of functionality (R²) on the cyclic keto enol ether, a rapid and facile dimerization occurs, giving spiroketal products. When the enone is substituted (i.e., R² = Ph), the cyclic keto enol ether is sufficiently stable so that it can be isolated; it can then be further reacted in the same pot to provide the corresponding dihydropyrazoles. Both the spiroketal and dihydropyrazole products arise by a tandem reaction that begins with the novel cycloisomerization. The method allows for the rapid introduction of complexity in the products from relatively simple starting materials. It should find application in the synthesis of natural product-like molecules

Hypoxia-Activated Small Molecule-Induced Gene Expression

<div><div><div><p>Hypoxia, conditions of reduced oxygen, occur in a wide variety of biological contexts, including solid tumours and bacterial biofilms, which are relevant to human health. Consequently, the development of chemical tools to study hypoxia is vital. Here we report a hypoxia-activated small molecule-mediated gene expression system using a bioreductive prodrug of the inducer isopropyl 1-thio-β-D-galactopyranoside (IPTG). As a proof-of-concept we have placed the production of a green fluorescent protein under the control of hypoxia. Our system has the potential to be extended to regulate the production any given protein of choice.</p></div></div></div