Synthesis of stable analogues of thiamine di- and triphosphate as tools for probing a new phosphorylation pathway

Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and the role of thiamine triphosphate is still especially unknown. To probe recent hypotheses on the implication of thiamine triphosphate in a new phosphorylation pathway involving synaptic proteins, we synthesized a series of thiamine di- and triphosphate analogues that are resistant to both enzymatic and chemical hydrolyses. The key step in the preparation of the title compounds is the coupling of thiamine propyl disulfide with adequately protected methylenebis-phosphonic acid, the corresponding triphosphate analogue, and difluoromethylenebisphosphonic acid.     

Acid-catalysed formation of tricyclic N,S-acetals in imidazolinone series based on the use of the unprecedented N-acyliminium ion cascade reaction involving transposition, heterocyclisation and pi-cyclisation

4-Hydroxy-5,5-dimethylimidazolines tethered at N-1 to an aryl sulfide undergo an unprecedented acid-catalysed domino reaction, involving double methyl transposition, heterocyclisation, isomerisation of thiazetidinium ion and, finally, pi-cyclisation. In this way a one-pot synthesis of original tricyclic N,S-acetals was developed. The same triheterocyclic products can be prepared also starting from the corresponding 5-hydroxy isomers (in this case the cascade of reactions does not involve methyl transposition).     

Synthesis and stereochemical resolution of functional [5]pericyclynes

Three different kinds of ring carbo-mers of [5]cyclitol ethers were targeted as challenging examples of functional [5]pericyclynes. Three tertiary pentaaryl-carbo-[5]cyclitol methyl ethers were synthesized through a [11+4] ring-closing double addition of triphenyl- and tri-p-anisyl-undecatetrayn-diides to dibenzoylacetylene. These compounds, obtained as oily mixtures of stereoisomers, are stable and can behave as acetylenic ligands of one or two Co₂(CO)₆ units. NMR analysis reveals that the broad diasteroisomeric dispersity of a triether, is consistently reduced in the symmetrized pentaether. Three bis-secondary triaryl-carbo-[5]cyclitol methyl ethers with adjacent CH(OR) vertices were synthesized through a similar [11+4] ring-closing process, where the same tetrayn-diides add to both the carbaldehyde ends of the (η²-OCH-CC-CHO)Co₂(CO)₆ complex. Despite the possibility of tautomeric isomerization, the occurrence of two adjacent bis-propargylic carbinol vertices does not diminish the stability of the [5]pericyclyne framework. Finally, two bis-secondary carbo-[5]cyclitol methyl ethers with non-adjacent CH(OH) vertices were synthesized through an alternative [10+5] ring-closing process. The bis-secondary carbo-[5]cyclitols are regarded as isohypsic equivalents of the challenging [C,C]₅carbo-cyclopentadienyl cation. A diphenyl-hexaoxy-[5]pericyclyne with two non-adjacent secondary carbinol vertices was also prepared through a [10+5] ring-closing strategy: this molecule is an isohypsic equivalent of the previously calculated zwitterionic carbo-cyclopentadienone, which could be observed as a DCI/NH₃-MS fragment after treatment with SnCl₂/HCl. Analytical HPLC showed that the C₁₁ triphenyl-undecatetrayne precursor of the [11+4] strategy was obtained as a statistical 1:2:1 mixture of the three possible diastereoisomers. Semi-preparative HPLC allowed for the resolution of this mixture. The pure major diastereoisomer was employed to prepare a partly resolved sample of pentamethoxy-pentaphenyl-[5]pericyclyne. Analytical HPLC showed that the latter corresponds to the statistical distribution of the expected three residual diastereoisomers. Semi-preparative HPLC finally afforded samples of diastereoisomerically pure pentamethoxy-[5]pericyclyne as crystalline solids.     

The total synthesis of 1-oxygenated eudesmane sesquiterpenes : (±) dihydroreynosin and (±) 1-oxocostic acid

The total synthesis of (±) dihydroreynosin $\text{1}$ and of (±) 1-oxocostic acid $\text{2}$ (R = H) are illustrative examples for a short entry into 1-oxygenated eudesmanes via an easily accessible key intermediate $\text{7}$.     

Facile synthesis of O6-alkyl-, O6-aryl-, and diaminopurine nucleosides from 2'-deoxyguanosine

The 3',5'-bis-O-TBDMS derivative of 2'-deoxyguanosine can be converted to its O6-alkyl and O6-aryl ethers as well as to N6-substituted diaminopurine nucleosides in two simple steps. Also described is a novel, nonaqueous, one-step O6-desulfonylation method that leads to deprotection of the carbonyl moiety of 2'-deoxyguanosine.     

新型显色剂3,3,5,5''''-四甲基联苯胺分光光度法测定余氯的研究

本文报道了采用新型氧化还原剂3,3’,5,5’-四甲基联苯胺(TMB)测定水中总余氯的分光光度法,并对其灵敏度、稳定性、准确性作了较为详细的研究,探讨了分析条件,提出了分析方法。在pH≤2时,最大吸收峰为450 nm,表观摩尔吸光系数为6.89×10~4L·mol~(-1)·cm~(-1),可测范围为0.01～2.5 mg/L。与目前使用的传统显色剂邻联甲苯胺(DMB)相比较,具有灵敏度高,显色稳定,重现性好及使用安全等优点。     

Aza-Diels-Alder reaction in fluorinated alcohols. A one-pot synthesis of tetrahydroquinolines

Hexafluoroisopropanol and trifluoroethanol are found to promote imino-Diels-Alder reactions of the N-aryl aldimine 1 with alkyl vinyl ethers to afford the corresponding tetrahydroquinolines in good yields without Lewis acid under mild and neutral conditions. The reaction is also efficient in a three component process from aldehyde, amine and vinyl ethers.     

Isotope shift and hyperfine structure measurements in titanium I

High accuracy measurements of hyperfine structure due to⁴⁷Ti and⁴⁹Ti in the 3d ² 4s ² a ³ F ₂?3d ² 4s4p z ⁵ D ₁ absorption line at σ=18482.772 cm^?1 have been performed by use of a Doppler-free experiment, where a beam of titanium atoms is crossed by a CW single mode tunable dye laser. They have allowed for the determination of isotope shifts between⁴⁶Ti,⁴⁷Ti,⁴⁸Ti,⁴⁹Ti and⁵⁰Ti. By use of accurate values of mean square nuclear charge radii for the even isotopes, it has been possible to separate mass shifts from field shifts and to determine accurate values for the mean square nuclear charge radii of⁴⁷Ti and⁴⁹Ti. The field shift presents a marked odd-even staggering.     

Comparison of Pyrolysis and Microwave Acid Digestion Techniques for the Determination of Mercury in Biological and Environmental Materials

 Microwave digestion reduction-aeration and pyrolysis combined with cold vapour atomic absorption and cold vapour atomic fluorescence are compared for the determination of total mercury in several biological and environmental matrices. The biological samples were digested in a mixture of HNO₃/H₂O₂, the environmental samples in a mixture of HNO₃/HClO₄. After reduction with SnCl₂, the mercury was collected by two-stage gold amalgamation. After microwave digestion reduction-aeration, detection limits of 1.4 ng g⁻¹ and 0.6 ng g⁻¹ were obtained for cold vapour atomic absorption spectrometry (CVAAS) and cold vapour atomic fluorescence spectrometry (CVAFS), respectively, for 250 mg of environmental samples. For biological samples (500 mg) the detection limits were 0.7 ng g⁻¹ (CVAAS) and 0.4 ng g⁻¹ (CVAFS). After pyrolysis, detection limits of 3.5 ng g⁻¹ and 1.6 ng g⁻¹ for CVAAS and CVAFS, respectively, were obtained for a 10 mg sample. Pyrolysis can only be applied when the organic content of the sample is not too high. Accurate results were obtained for 8 certified reference materials of both environmental and biological origin. In addition, a real sludge sample was analysed. Author for correspondence. E-mail: richard.dams@rug.ac.be Received September 18, 2002; accepted December 3, 2002 Published online May 5, 2003