Intramolecular cycloadditions of keteniminium salts. A practical asymmetric synthesis of prostaglandins.

The intramolecular [2 + 2] cycloaddition of keteniminium salt 5 derived from (2S, 5S)-dimethylpyirolidine is the key step of a short synthetic route toward prostaglandins.     

Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrones.

Efficient routes to the synthesis of norbornadiene-tethered nitrones have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in moderate to good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.     

Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrile oxides.

Efficient routes to the synthesis of norbornadiene-tethered nitrile oxides have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.     

Intramolecular cycloadditions of cyclobutadiene with olefins

Intramolecular cycloadditions between cyclobutadiene and olefins can provide highly functionalized cyclobutene-containing products. The outcome of the reaction depends on the nature of the tether connecting the two reactive partners in the cycloaddition. Electronically unactivated olefins attached to cyclobutadiene through a three-atom, heteroatom-containing tether yield successfully the desired cycloadducts, whereas the corresponding substrates without a heteroatom linkage or with a longer tether are less prone to undergo the intramolecular cycloaddition. Calculations were used to help uncover some of the factors that influence the course of the cycloaddition. Successful intramolecular reactions usually require either electronic activation of the dienophile, conformational restriction of the tether, or a slower oxidation protocol. In general, a facile intermolecular dimerization of cyclobutadiene is the major process that competes with the intramolecular cycloaddition.     

Intramolecular diels-alder cycloadditions of bis-diene substrates

Unique internal competition in the intramolecular cycloaddition of bis-diene substrates occurs with high stereoselectivity. Aqueous reaction conditions promote coiling of the lipophilic chain which alters the observed regioselectivity.     

Intramolecular oxime olefin cycloadditions. Stereospecific formation of functionalized pyrrolidines.

Allylamines possessing a properly positioned aldoxime or ketoxime chain undergo thermally induced dipolar cycloaddition to bicylic isoxazolidines, with stereospecific introduction of three stereo centers. This provides an entry into stereospecifically functionalized pyrrolidines.     

A novel approach to the synthesis of 8-methyl prostaglandins

A synthesis of 8-methyl prostaglandins is described. Starting from a chiral cyclic keto lactone, C₁-homologation with dimethyl oxosulfonium methylide is used as key reaction in the sequence. 8-Methyl prostaglandin C₂ and its methyl ester proved to be quite unstable due to double-bond migration and dehydration.     

Synthetic studies toward diazonamide A. A novel approach for polyoxazole synthesis

[Reaction in text]The indole-bisoxazole fragment of diazonamide A was prepared by a Chan-type rearrangement of a tertiary amide. This approach represents a remarkably direct strategy for polyoxazole synthesis.     

Intramolecular diels-alder cycloadditions of vinylketenimines. A convergent route to carbazoles and pyridocarbazole alkaloids

The intramolecular Diels-Alder cycloaddition of acetylenic vinylketenimines is the key step of a highly convergent synthesis of carbazoles. A facile synthesis of N-methyl-tetrahydroellipticine has been completed in five isolated steps from N-methyl piperidone.     

Intramolecular azide-diene cycloadditions. An approach to fused bicyclic 3-pyrrolines based on a one-pot nitrene-diene cycloaddition equivalent.

Cyclization of heterosubstituted ω-azidodienes 11 provides fused bicyclic 3-pyrrolines 12 in one operation. These pyrrolines are potentially useful intermediates for natural products synthesis, as illustrated by further functionalization.     

Intramolecular 1,3-dipolar cycloadditions of aliphatic nitrile oxides

Treatment of functionalized 1-chloro-oximes ( 3c and 4a,b ) with triethylamine originates nitrile oxides ( 1c and 2a,b ) which undergo an intramolecular cycloaddition providing fused-ring isoxazole derivatives ( 7c and 8a,b ). The latter reaction was not observed for one substrate ( 2c ).     

A novel approach toward low optical band gap polysquaraines

[reaction: see text] Polycondensation of 2,5-dialkoxydivinylbenzene-bridged bispyrroles and squaric acid resulted in extensively conjugated polymers with strong near-infrared (NIR) absorption around 800-1000 nm, which is a signature of their low band gap (E(g)). Conjugated polymers with such a strong NIR absorption are rare. One of the synthesized polysquaraines showed a significantly low E(g) of 0.79 eV with an intrinsic conductivity of 5.3 x 10(-4) S/cm.     

Intramolecular cycloadditions of nitrones joined by amides to olefins

Six nitrones joined by amides to olefins were prepared in situ from the related ketones 1–3 with N-methy]- and benzylhydroxylamines. The nitrones added intramolecularly to the olefins, and the cycloadditions gave the 6-lactams 4–9 stereoselectively and regiospecifically. Chemical correlations, CMR spectroscopy and two X-ray crystallographic analyses established that the relative stereochemistries of the six cycloadducts 4–9 were identical.     

Intramolecular photochemical dioxenone-alkene [2 + 2] cycloadditions as an approach to the bicyclo[2.1.1]hexane moiety of solanoeclepin A.

A synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes, was approached via an intramolecular [2 + 2] photocycloaddition. Aldehyde 12 containing the dioxenone chromophore served as a useful starting material, allowing the synthesis of a variety of photocycloaddition substrates via Grignard addition or via a Nozaki-Hiyama-Kishi reaction. Photolysis of the unsubstituted alkene 14 led to the expected crossed cycloadduct bicyclo[2.1.1]hexane 15 according to the so-called rule of five. However, several functionalized alkenes 18, 20, and 31 exhibited a complete reversal of cycloaddition regioselectivity, providing straight cycloadducts bicyclo[2.2.0]hexanes 21-26 and 4, respectively. Their structures were proved by a combination of extensive NMR measurements, X-ray analyses, and subsequent retro-aldol reactions. The latter de Mayo process allowed the formation of spiro-[3.5]nonane 35 and spiro[3.4]octane 36 as well as the cyclobutanes 37 and 38. Finally, the cyclization of the more rigid lactone precursor 28 occurred in high yield in the desired fashion with complete regio- and stereoselectivity to give 3 containing the core bicyclo[2.1.1]hexane skeleton of the natural product.     

A multilayer screening approach toward the discovery of novel Pf-DHFR inhibitors

A small yet diverse xanthone library was build and computationally docked against wild type Pf-DHFR by Molegro Virtual Docker (MolDock). For analysis of results an integrated approach based on re-ranking, scaling (based on heavy atom counts), pose clustering and visual inspection was implemented. Standard methods such as self-docking (for docking), EF analysis, average rank determinations (for size normalization), and cluster quality indices (for pose clustering) were used for validation of results. Three compounds X5, X113A and X164B displayed contact footprints similar to the known inhibitors with good scores. Finally, 16 compounds were extracted from ZINC data base by similarity based screening, docking score and drug/lead likeness. Out of these 16 compounds, 11 displayed very close contact footprints to experimentally known inhibitors, indicating there potential utility in further drug discovery efforts.     

Intramolecular cycloadditions of bis-o-xylyenes. an extremely short route to [2.2.2]cyclophanes.

Benzocyclobutenes linked by two-carbon bridges undergo flashpyrolytic conversion to [2.2.2]cyclophanes.