Synthesis of an ethidium nucleoside and its acyclic analog

The protected ethidium nucleosides 8-(3′,5′-di-O-benzoyl-2′-deoxy-d-ribofuranosyl)-3-acetamido-5-ethyl-6-phenyl-phenanthridinium (5), 8-(3′,5′-di-O-acetyl-2′-deoxy-d-ribofuranosyl)-3-acetamido-5-ethyl-6-phenyl-phenanthridinium (6), and the acyclic analog 8-[(3R)-1,3-dihydroxy-4-yl]-acetamido-3-amino-5-ethyl-6-phenyl-phenanthridinium (3) were prepared. Based on to their different stability, only the acyclic derivative 3 seems to be suitable for oligonucleotide synthesis. Furthermore, the acyclic ethidium nucleoside analog 3 exhibits comparable absorption and emission properties of the underivatized ethidium (1).     

Synthesis of acyclic nucleoside phosphonates as antiviral compounds

Reaction of 6‐chloropyrimidines with diethyl [(2‐aminoethoxy)methyl]phosphonate allows for a ready access to acyclic nucleoside phosphonates. A series of 5‐substituted pyrimidines bearing a phosphonate side chain at position 6 were synthesized and tested against herpes simplex viruses (HSV‐1 and HSV‐2) and human immunodeficiency virus (HIV‐1). Some compounds showed weak antiviral activity against HSV‐1.     

A highly fluorescent nucleoside analog based on thieno[3,4-d]pyrimidine senses mismatched pairing

A highly emissive nucleobase analog, based on a thieno[3,4-d]pyrimidine core, is enzymatically incorporated into RNA oilgonucleotides that function as base discriminating fluorescent probes.     

Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety

With respect to the strong antiviral activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine various types of its side chain fluorinated analogues were prepared. The title compound, (S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]-5-azacytosine (FPMP-5-azaC) was synthesised by the condensation reaction of (S)-2-[(diisopropoxyphosphoryl)methoxy)-3-fluoropropyl p-toluenesulfonate with a sodium salt of 5-azacytosine followed by separation of appropriate N¹ and O² regioisomers and ester hydrolysis. Transformations of FPMP-5-azaC to its 5,6-dihydro-5-azacytosine counterpart, amino acid phosphoramidate prodrugs and systems with an annelated five-membered imidazole ring, i.e. imidazo [1,2-a][1,3,5]triazine derivatives were also carried out. 1-(2-Phosphonomethoxy-3,3,3-trifluoropropyl)-5-azacytosine was prepared from 5-azacytosine and trifluoromethyloxirane to form 1-(3,3,3-trifluoro-2-hydroxypropyl)-5-azacytosine which was treated with diisopropyl bromomethanephosphonate followed by deprotection of esters. Antiviral activity of all newly prepared compounds was studied. FPMP-5-azaC diisopropyl ester inhibited the replication of herpes viruses with EC₅₀ values that were about three times higher than that of the reference anti-HCMV drug ganciclovir without displaying cytotoxicity.     

Synthesis and characterization of highly fluorescent indenofluorenes

[structure: see text] Described here are the synthesis and optical and electrochemical properties of a series of indenofluorenes as new building blocks for electronic and optoelectronic materials.     

Synthesis of a highly fluorinated fatty acid analog

A five-step synthesis of Z-11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,18,18-heptadecafluoro-octadec-8-enoic acid is reported, starting from 1,8-octanediol and 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-heptadecafluoro-10-iododecane. The key step is a Wittig reaction to form the C8-C9 double bond with a Z:E isomeric ratio of 10:1. The route should be generally applicable to the synthesis of highly fluorinated monounsaturated fatty acids.     

Synthesis of highly fluorescent materials: Isoindole-containing polymers

A series of stable, highly fluorescent and highly phenylated isoindoles have been synthesized by treating the respective o-dibenzoylbenzenes with anilines at 200°C in the presence of a catalytic amount of p-toluenesulfonic acid. The correlation between the emission frequences and the structures of the isoindoles is described. The same reaction has also been used to transform a series of poly(o-dibenzoylbenzene)s into poly(isoindole)s. The resulting polymers have been studied by ¹H-NMR, DSC, TGA, and fluorescence spectra. They are highly fluorescent materials with high molecular weights, high glass transition temperatures, and high thermal stabilities. The tetraphenyl substituted isoindole-containing polymers have a maximum emission around 468 nm, whereas the diphenyl substituted isoindole-containing polymers have their maximum emission around 486 nm. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3293–3299, 1999     

Synthesis and stability of oligonucleotides containing acyclic achiral nucleoside analogues with two base moieties

[structure: see text] Nucleotide building blocks with two base moieties were synthesized and incorporated into oligonucleotides. One of the two bases is involved in base pairing within the double helix, while the other base is sticking out of the minor groove. This system may be used for presenting sequence information at the outside of the helix.     

Synthesis of a new family of acyclic nucleoside phosphonates, analogues of TPases transition states

A 6-step procedure was developed for the synthesis of a new family of acyclic nucleoside phosphonates (ANPs), "PHEEPA" [(2-pyrimidinyl-2-(2-hydroxyethoxy)ethyl)phosphonic acids] in overall yields ranging from 4.5% to 32%. These compounds, which possess on one side a hydroxy function and on the other side a phosphonate group, can be considered either as potential antiviral agents or as transition state analogues of nucleoside phosphorylases such as thymidine phosphorylase.     

Synthesis of a solvent-sensitive highly fluorescent derivative of perfluorocyclopentene

A solvent-sensitive highly fluorescent compound, N-[2-(1′,3′,4′,4′,5′,5′-hexafluorocyclopentenyl)]-4-(5-methoxy-thiazolyl)pyridine (1D) was synthesized as an unexpected product of the reaction of 4-bromo-5-methoxy-2-(4-pyridyl)thiazole (1B) with perfluorocyclopentene in the presence of n-BuLi. Primary mechanism of this reaction was proposed, and the photophysical properties of 1D in different solvents were studied.     

Synthesis of acyclic nucleoside analogs of 6-substituted 2-aminopurines and 2-amino-8-azapurines

Several new acyclonucleoside purine and 8-azapurine analogs have been prepared from 2-amino-4,6-dichloropyrimidine ( 1 ) and 3-amino-1,2-propanediol ( 2a ) and 4-amino-1-butanol ( 2b ), respectively, as the starting materials. The new target compounds are: 2-amino-6-chloro-9-(2,3-dihydroxypropyl)purine ( 6a ), 2-amino-6-chloro-9-(4-hydroxybutyl)purine ( 6b ), 2-amino-6-chloro-9-(2,3-dihydroxypropyl)-8-azapurine ( 7a ), 2-amino-6-chloro-9-(4-hydroxybutyl)-8-azapurine ( 7b ), 9-(2,3-dihydroxypropyl)-8-azaguanine ( 8a ), 9-(4-hydroxybutyl)-8-azaguanine ( 8b ), 9-(2,3-dihydroxypropyl)-8-azathioguanine ( 9a ), and 9-(4-hydroxybutyl)-8-azathioguanine ( 9b ). Also, the requisite intermediate pyrimidine derivatives, 2,5-diamino-4-(2,3-dihydroxypropylamino)-6-chloropyrimidine ( 5a ) and 2,5-diamino-4-(4-hydroxybutylamino)-6-chloropyrimidine ( 5b ) are novel.     

Synthesis of highly fluorescent and water soluble perylene bisimide

Designed and synthesized a new highly water soluble N,N¹-bis（2-（（5-（（dimethylamino）methyl）furan-2-yl）methylthio）ethyl）-perylene -3,4,9,10-tetracarboxylic diimide from 2-（（5-（（dimethylamino）methyl）furan-2-yl）methylthio）ethanamine and perylene-3,4,9,10- tetracarboxylic dianhydride.The compound was characterized by ¹H,¹³C,2D NMR,mass and IR techniques.The compound is highly fluorescent with good solubility in water and other polar solvents.     

Synthesis of an antimony rhodamine analog

We describe the synthesis, structure and characterization of an antimony-rhodamine derivative with a phenyl-antimony moiety installed at the 10' position of the central ring. This compound is a red fluorophore (λ_em = 655 nm) with a quantum yield of 12% in acetonitrile.     

Synthesis and properties of 5-cyano-substituted nucleoside analog with a donor-donor-acceptor hydrogen-bonding pattern

6-Aminopyridin-2-ones form Watson-Crick pairs with complementary purine analogues to add a third nucleobase pair to DNA and RNA, if an electron-withdrawing group at position 5 slows oxidation and epimerization. In previous work with a nucleoside analogue trivially named dZ, the electron withdrawing unit was a nitro group. Here, we describe an analogue of dZ (cyano-dZ) having a cyano group instead of a nitro group, including its synthesis, pK(a), rates of acid-catalyzed epimerization, and enzymatic incorporation.