Efficient synthesis of various acycloalkenyl derivatives of pyrimidine using cross-metathesis and Pd(0) methodologies

Novel acyclonucleosides (9a-d, 10a-d, 18a,b and 19a,b) have been prepared using Pd(0) and cross-metathesis methodologies. The allylic N-alkylation under Tsuji-Trost conditions was used to introduce the nucleobase, while the Suzuki-Miyaura reaction afforded C-5 substituted uracil analogues. The cross-metathesis performed with a ruthenium catalyst was used to provide new acycloalkenyl nucleosides. The antiviral activities of all final compounds have been evaluated.     

Bitriazolyl acyclonucleosides with antiviral activity against tobacco mosaic virus

Bitriazolyl acyclonucleosides were synthesized via the Huisgen reaction and then subjected to ammonolysis. The antiviral activity of these nucleosides against tobacco mosaic virus (TMV) was assessed. Like the previously described bitriazolyl compounds, these new bitriazolyl acyclonucleosides were found to show anti-TMV activity. This suggests that the bitriazolyl moieties are important structural features involved in the antiviral activity of these compounds.     

Synthesis of 1-[(3-Halo-1-Hydroxy-2-Propoxy)methyl]uracil and Thymine as Potential Antiviral Agents

3′-Halogen acyclonucleoside analogs have been prepared. The starting material, benzyl glycidyl ether (5) , prepared from eplchlorohydrin and sodium benzyloxidc, underwent ring opening by soft halogen ions to give l-benzyloxy-3-fluoro-2-propanol (6) , l-bcnzyloxy-3-chloro-2-propanol (7) , and l-benzyloxy-3- bromo-2-propanol (8) respectively. The treatment of 5 with lithium iodide in the presence of acetic acid provided 1-benzyloxy-3-iodo-2-propanol (9) . The treatment of 8 with sodium iodide in anhydrous acetone also produced l-benzyloxy-3-iodo-2-propanol (9) . Chloromethylation of these halohydrins 6-9 using paraformaldehyde and hydrogen chloride gas produced the chloromcthyl ethers 10-13 . These chloromethyl ethers without further purification were allowed to react with the silylated bases 16-17 , previously prepared by silylating the bases 14-15 with HMDS in the presence of ammonium sulfate to give 1- [(l-benzyloxy-3-halogen-2-propoxy)methyl]uracils and thymines 19-25 . The target compounds 26-33 were obtained respectively after the debcnzylation of 18-25 . Compounds 26, 27, 30 and 31 had no significant cell toxicity in the range of concentrations 0.001-20 mM. Compounds 26, 27, 28 and 29 have no significant activity against HSV II (for less than 2 mM there is a cytopathic effect). Compounds 30, 31, 32 and 33 show no activity against HSV II virus even at the level 20 mM.     

Acyclic Analogues of Purine Nucleosedes: One- and Two-Dimensional 1H and 13C NMR Evidences for N-9 and N-7 Regioisomers

It has been established by means of one-and two-dimensional ¹H and ¹³C NMR Spectroscopy that adenine acyclonucleosides are substituted at either N-9 or N-7 with 2',3'-dihydroxyprop-1-yl (2 and 3) or 2'-hydroxyprop-1-yl (4 and 5) aliphatic chains. The N-3 isomer has not been formed, as claimed previously. This was deduced on the basis of chemical shifts, substituent induced chemical shifts, magnitude and multiplicity of C-H couplings as well as connectivities in 2D homo-and heteronuclear correlation spectra.     

Simple Analogues of Acyclonucleosides: Synthesis of N‐Substituted Pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine Derivatives

The synthesis of N‐substituted pyridothienopyrimidines bearing ethoxymethyl, benzyloxymethyl, methylthiomethyl, benzoylmethyl, allyl, sec‐butyl, and 2‐acetyloxyethyl chains as a sugar mimic was described. The O‐substituted pyridothienopyrimidines were obtained during some reactions.     

MAOS of D‐Gluconic Acid,D‐Glucono‐1,4‐ and 1,5‐Lactones,Esters, Hydrazides,and Benzimidazoles Thereof

Microwave‐assisted organic synthesis (MAOS) of D‐gluconic acid can be efficiently done by oxidation of D‐glucose with bromine water, upon irradiation with microwave (MW). It was also used for the conversion of D‐gluconic acid to ethyl D‐gluconate, D‐glucono‐1,4‐ and 1,5‐lactones, gluconyl hydrazide, and gluconyl phenylhydrazide in yields comparable to those obtained by conventional methods, but in much shorter times. A convenient microwave‐mediated condensation of D‐gluconic acid with o‐phenylenediamines provided the respective acyclonucleoside benzimidazole in short time and good yield.