Regiospecific and highly stereoselective coupling of 6-(substituted-imidazol-1-yl)purines with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride. Sodium-salt glycosylation in binary solvent mixtures: improved synthesis of cladribine

Glycosylation of 6-(substituted-imidazol-1-yl)purine sodium salts with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride proceeds with regiospecific formation of the N9 isomers. Base substrates with lipophilic substituents on the C6-linked imidazole moiety are more soluble in organic solvents, and the solubility is further increased with binary solvent mixtures. Selective solvation also diminishes the extent of anomerization of the chlorosugar. Stirred reaction mixtures of the modified-purine sodium salts generated in a polar solvent and cooled solutions of the protected 2-deoxysugar chloride in a nonpolar solvent give 2'-deoxynucleoside derivatives with N9 regiochemistry and enhanced beta/alpha configuration ratios. Application of the binary-solvent methodology with 2-chloro-6-(substituted-imidazol-1-yl)purine salts in cold acetonitrile and the chlorosugar in cold dichloromethane gives essentially quantitative yields of the N9 isomers of beta-anomeric 2'-deoxynucleoside intermediates. Direct ammonolysis (NH(3)/MeOH) of such intermediates or benzylation of the imidazole ring followed by milder ammonolysis of the imidazolium salt gives high yields of the clinical anticancer drug cladribine (2-chloro-2'-deoxyadenosine).     

Energy levels of iodine-129 near the B state dissociation limit from two-photon spectroscopy

Two-photon sequential absorption spectroscopy has been used to selectively excite rotational structure in the B---X absorption transition of the ¹²⁹I₂ molecule up to within 2 cm⁻¹ of the dissociation limit. Vibrational and rotational constants have been obtained for the B state levels with υ = 71–79. Le Roy's equations for long-range behaviour are expressed in mass-reduced form, and it is shown that these equations can be successfully used to combine the spectroscopic constants for ¹²⁷I₂ and ¹²⁹I₂ to give improved values of the long range constants for the B state. The improved values are only slightly different from those previously obtained by the same technique for ¹²⁷I₂ alone.     

Synthesis and single-crystal X-ray diffraction analysis of 2-sulfamoyladenosine (6-amino-9-β-D-ribofuranosylpurine-2-sulfonamide)

2-Amino-9-β-D-ribofuranosylpurine-2-sulfonamide (2-sulfamoyladenosine, 4 ), a congener of sulfonosine ( 3 ), was synthesized by four different routes. Acid catalyzed fusion of 6-chloropurine-2-sulfonyl fluoride ( 5 ) with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose ( 8 ) gave a good yield of 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine-2-sulfonyl fluoride ( 9 ). Ammonolysis of 9 furnished 4 . Lewis acid catalyzed glycosylation of the trimethylsilyl derivative of either 6-chloropurine-2-sulfonamide ( 6 ) or 6-aminopurine-2-sulfonamide ( 7 ) with 8 gave the corresponding N9-glycosylated products, 10 and 11 , respectively, which on ammonolysis gave 4 . Amination of 2-thioadenosine ( 12 ) with chloramine solution gave the sulfenamide derivative 13 , which on subsequent oxidation with m-chloroperoxybenzoic acid furnished an alternate route to 4 . The structure of 4 was established by single-crystal X-ray diffraction studies. 2-Sulfamoyladenosine ( 4 ) is devoid of significant inhibitory activity against L1210 leukemia in mice.     

Atom lasers: Production,properties and prospects for precision inertial measurement

We review experimental progress on atom lasers out-coupled from Bose–Einstein condensates, and consider the properties of such beams in the context of precision inertial sensing. The atom laser is the matter-wave analogue of the optical laser. Both devices rely on Bose-enhanced scattering to produce a macroscopically populated trapped mode that is output-coupled to produce an intense beam. In both cases, the beams often display highly desirable properties such as low divergence, high spectral flux and a simple spatial mode that make them useful in practical applications, as well as the potential to perform measurements at or below the quantum projection noise limit. Both devices display similar second-order correlations that differ from thermal sources. Because of these properties, atom lasers are a promising source for application to precision inertial measurements.     

The Crystal Structure of 1,2-Didehydrocrotalanine Picrate: A Macrocyclic Pyrrolizidine Alkaloid Analogue

1,2-Didehydrocrotalanine ( 2 ) is the first synthetic macrocyclic pyrrolizidine alkaloid analogue to be studied by X-ray crystallography. The crystal structure was solved by multisolution direct methods and refined by full-matrix least-squares to R = 0.036 for 693 reflections. The alkaloid analogue has an 11-membered macrocycle containing two ester groups with their carbonyl groups nearly antiparallel.     

A facile synthesis of new 5H-indazolo[3,2-b]benzo[d]-1,3-oxazines via one-pot intramolecular Bis-heterocyclizations

The parent 5H-indazolo[3,2-b]benzo[d]-1,3-oxazine heterocycle as well as a series of novel analogues have been synthesized utilizing two subsequent intramolecular heterocyclizations in one pot. A variety of diversity groups were added to explore the scope of this reaction and to provide a number of new compounds for biological screening.     

Correlation between the synthetic origin of methamphetamine samples and their 15N and 13C stable isotope ratios

The active ingredient of ecstasy, N-methyl-3,4-methyldioxyphenylisopropylamine (MDMA) can be manufactured by a number of easy routes from simple precursors. We have synthesised 45 samples of MDMA following the five most common routes using N-precursors from 12 different origins and three different precursors for the aromatic moiety. The ¹³C and ¹⁵N contents of both the precursors and the MDMA samples derived therefrom were measured by isotope ratio mass spectrometry coupled to an elemental analyser (EA-IRMS). We show that within-pathway correlation between the ¹⁵N content of the precursor and that of the derived MDMA can be strong but that no general pattern of correlation can be defined. Rather, it is evident that the δ¹⁵N values of MDMA are strongly influenced by a combination of the δ¹⁵N values of the source of nitrogen used, the route by which the MDMA is synthesised, and the experimental conditions employed. Multivariate analysis (PCA) based on the δ¹⁵N values of the synthetic MDMA and of the δ¹⁵N and δ¹³C values of the N-precursors leads to good discrimination between the majority of the reaction conditions tested.     

Addition of difluorocarbene to 3',4'-unsaturated nucleosides: synthesis of 2'-deoxy analogues with a 2-oxabicyclo[3.1.0]hexane framework

Treatment of protected 2'-deoxy-3',4'-unsaturated nucleosides derived from adenosine and uridine with difluorocarbene [generated from bis(trifluoromethyl)mercury and sodium iodide] gave fused-ring 2,2-difluorocyclopropane compounds. Stereoselective alpha-face addition to the dihydrofuran ring resulted from hindrance by the protected beta-anomeric nucleobases. A protected uracil compound was converted smoothly into the cytosine derivative via a 4-(1,2,4-triazol-1-yl) intermediate. Removal of the protecting groups gave new difluorocyclopropane-fused nucleoside analogues. The solid-state conformation of the nearly planar furanosyl ring in the uracil compound had a shallow 2E pucker, and a more pronounced 1E conformation was present in the furanosyl ring of the cytosine derivative.     

Synthesis and single-crystal X-ray diffraction studies of 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide and certain related nucleosides

1-β-D-Ribofuranosyl- 21 , 1-(2-deoxy-β-D-erytftro-pento fur anosyl)- 27 and 1-β-D-arabinofuranosyl- 29 derivatives of 1,2,4-triazole-3-sulfonamide ( 19 ) have been prepared. Glycosylation of the silylated 19 with 1,2,3,5-tetra-0-acetyl-β-D-ribofuranose ( 5 ) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleoside ( 20 ), which on ammonolysis afforded 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide ( 21 ). Stereospecific glycosylation of the sodium salt of 19 with either 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 22 ) or 1-chloro-2,3,5-tri-0-benzyl-α-D-arabinofuranose ( 23 ) provided the corresponding protected nucleosides 26 and 28. Deprotection of 26 and 28 furnished 1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,4-triazole-3-sulfonamide ( 27 ) and 1-β-D-arabinofuranosyl-1,2,4-triazole-3-sulfonamide ( 29 ), respectively. 2-0-D-Ribofuranosyl-1,2,4-triazole-3(4H)-thione ( 7 ) and 4-β-D-ribofuranosyl-1,2,4-triazole-3(2H)-thione ( 9 ) were also prepared utilizing either an acid catalyzed fusion of 1,2,4-triazole-3(1H,2H)-thione ( 4 ) with 5 , the reaction of 5 with silylated 4 in the presence of trimethylsilyl triflate, or by ring closure of 4-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)thiosemicarbazide ( 10 ) with mixed anhydride and subsequent deacylation. The synthesis of 1-β-D-ribofuranosyl-3-benzylthio-1,2,4-triazole ( 15 ) has also been accomplished by the silylation procedure employing 3-benzylthio-1,2,4-triazole ( 13 ) and 5 to give 1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)-3-benzylthio-1,2,4-triazole ( 14 ). Deacetylation of 14 furnished 15 . The structural assignments of 7, 14 and 21 were made by single-crystal X-ray diffraction analysis and their hydrogen bonding characteristics have been studied. The sulfonamido-1,2,4-triazole nucleosides are devoid of any significant antiviral or antitumor activity in cell culture.