1,720,997 research outputs found
Synthesis of N-heterocyclic compounds via ene-yne metathesis reactions
No full textPropargylamino and allylamino derivatives of cyclohexene and norbornene were subjected to tandem metathesis reactions with first and second generation Grubbs' catalysts 1 and 2. Results show that the method is compatible with suitably protected nitrogen-containing compounds. Cyclohexenes gave intriguing results in terms of the possibility to perform ring rearrangement metathesis (RRM) reactions, showing a difference with the analogous allyl and propargyl ether substrates. © 2007 Elsevier Ltd. All rights reserved
Nucleoside Phosphate-Conjugates Come of Age: Catalytic Transformation, Polymerase Recognition and Antiviral Properties
No full textOver the past few decades, different types of nucleoside phosphate-conjugates have been under extensive investigation due to their favorable molecular lability with interesting catalytic hydrolysis mechanisms, recognition as polymerase substrates, and especially for their development as antiviral/ anticancer protide therapeutics. The antiviral conjugates such as nucleoside phosphoesters and phosphoramidates that were discovered and developed in the initial years have been well reviewed by the pioneers in the field. In the present review, we will discuss the basic chemical and biological principles behind consideration of some representative structural classes. We will also summarize the chemical and biological properties of some of the more recent analogues that were synthesized and evaluated in our laboratory and by others. This includes new principles for their application as direct substrates of polymerases, nucleobasedependent catalytic and antiviral activity, and a plausible 'prodrug of a prodrug' strategy for tissue/organ-specific targeted drug delivery.sponsorship: The research leading to these results has received funding from FWO Vlaanderen, Belgium (G078014N). (FWO Vlaanderen, Belgium|G078014N)status: Publishe
Corrigendum to "Synthesis of N-heterocylic compounds via ene-yne metathesis reactions" [Tetrahedron 64(1) (2008) 204-218] (DOI:10.1016/j.tet.2007.10.076)
No full textAlkene and enyne metathesis reactions on allylic and propargylic amines
No full textTreatment of cis-4,5-diaminocyclohexene derivatives bearing allyl or propargyl groups on the nitrogen atoms, with first or second generation Grubbs metathesis catalysts, results in initiation of metathesis cascades which include ring-opening of the unstrained cyclohexene ring. This contrasts with the previous work on the analogous cyclohexene ethers where metathesis reactions occurred exclusively between the side-chains and no ring-opening of the cyclohexene unit was observed. © 2007 Elsevier Ltd. All rights reserved
Synthesis of cyclic and macrocyclic ethers using metathesis reactions of alkenes and alkynes
No full textThe metathesis transformations of cyclohexanes and cyclohexenes bearing allylic and/or propargylic ether substituents has been investigated. A range of products containing fused 6,8-bicyclic ring systems resulting from alkene and/or enyne metatheses were obtained using first and second generation, well defined alkylidene ruthenium catalysts. However, the unstrained cyclohexene unit did not participate in any of these metathesis processes, even though doing so would have led to a thermodynamically more stable product. This contrasts with previous results on similar compounds and on the corresponding amino-substituted cyclohexenes. The synthesis of dienes and dihydrofurans by metathesis processes involving the side chains of suitable cyclohexene ethers is also reported. When the unstrained cyclohexene unit was replaced by a norbornene group, the strained alkene did participate in a cascade of alkene and enyne metatheses. This chemistry was extended to alkyne metatheses of cyclohexene and norbornene esters, leading to 6,12-fused cycloalkynes which would subsequently undergo further enyne and/or alkene metatheses. This culminated in the development of the first one-pot metathesis process in which alkyne, enyne and alkene metathesis reactions initiated by two different catalysts all occur sequentially to form a 5,12-fused bicyclic diene product. © Wiley-VCH Verlag GmbH & Co. KGaA, 2007
Overview of Biologically Active Nucleoside Phosphonates
Full text linkThe use of the phosphonate motif featuring a carbon-phosphorous bond as bioisosteric replacement of the labile P-O bond is widely recognized as an attractive structural concept in different areas of medicinal chemistry, since it addresses the very fundamental principles of enzymatic stability and minimized metabolic activation. This review discusses the most influential successes in drug design with special emphasis on nucleoside phosphonates and their prodrugs as antiviral and cancer treatment agents. A description of structurally related analogs able to interfere with the transmission of other infectious diseases caused by pathogens like bacteria and parasites will then follow. Finally, molecules acting as agonists/antagonists of P2X and P2Y receptors along with nucleotidase inhibitors will also be covered. This review aims to guide readers through the fundamentals of nucleoside phosphonate therapeutics in order to inspire the future design of molecules to target infections that are refractory to currently available therapeutic options.status: Publishe
Ene-yne metathesis of polyunsaturated norbornene derivatives
Full text linkNorbornene derivatives bearing endo-substituents in the 5- and 6-positions were studied as substrates for ene-yne metathesis cascades. Substrates which contained an internal alkyne and a terminal alkene or alkyne in each sidechain were found to undergo a metathesis cascade leading to pentacyclic bis-dienes and bis-trienes. Attempts to extend the chemistry further to sidechains containing two internal alkynes or two internal alkynes and a terminal alkene were not successful with the first generation Grubbs' catalyst. However, the substrate containing two internal alkynes did react with the second generation Grubbs' catalyst to give a tetra-diene containing product. Ruthenium based metathesis initiators have been used to convert readily available norbornene derivatives bearing polyunsaturated sidechains into highly functionalised polycyclic compounds. © 2004 Elsevier Ltd. All rights reserved
Synthesis of oxygen-containing medium and large rings using one-pot combinations of sequential alkene, enyne and alkyne metathesis reactions
No full textThe first and second generation Grubbs' catalysts are shown to convert cyclohexane and cyclohexene bis-allyl and allyl propargyl ethers into 6,8-fused bicyclic derivatives by alkene and enyne metathesis reactions, respectively. The corresponding cyclohexane and cyclohexene bis-propargyl ethers are converted into 6,8-fused bicyclic trienes by enyne metathesis when treated with the second generation Grubbs' catalyst. Cyclohexene and norbornene esters bearing two alkyne units undergo alkyne metathesis when treated with molybdenum hexacarbonyl and 2-fluorophenol to give 12-membered ring containing alkynes which subsequently undergo alkene and enyne metathesis reactions when treated with first or second generation Grubbs' catalysts. Both Grubbs' catalysts are shown to be compatible with the reagents and conditions used for the molybdenum alkyne metathesis catalyst, thus allowing the two catalysts to be used in a one-pot process involving alkyne, enyne and alkene metathesis transformations. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA
Uncommon Three-, Four-, and Six-Membered Nucleosides
No full textOver the past two decades, nucleoside analogues exhibiting uncommon sugar moieties rather than natural ribo‐ and 2′‐deoxyribofuranose rings have received growing attention because of the increased recognition of their various biological roles. In particular, countless reports have been published that describe the value of ring‐contracted analogues based on a three or four‐membered pseudo‐sugar unit in the treatment of viral infections. Within this latest context, the pursuit of carbocyclic nucleosides structurally related to natural furanose units has been driven by their distinguishing stability toward chemical and metabolic degradation, due to the absence of an anomeric center. In an effort to generate more effective therapeutics through modifications of the carbohydrate moiety of nucleosides, many powerful and innovative transformations have been accomplished, which led to the creation of an important structural variety, including three‐, four‐, and six‐membered ring analogues
Synthesis of Phosphonoglycine Backbone Units for the Development of Phosphono Peptide Nucleic Acids
No full textA series of phosphono-modified backbone mimics based on achiral and chiral N-(dihydroxypropyl)glycine units were obtained by sequential addition of phosphonate and nucleobase moieties to suitably protected dihydroxypropylamines. Simple synthetic strategies enabled the preparation of various target derivatives that will be useful as building blocks for the preparation of new synthetic polymers containing a phosphonate internucleotide linkage in place of the standard phosphodiester bond.status: Publishe
- …
