The synthesis of 1,5-anhydrohexitol nucleosides is described. These nucleoside analogues were obtained by alkylation of the heterocyclic bases with the tosylate 10 or by alkylation of the bases with the alcohol 12 under Mitsunobu conditions. The compounds were evaluated for antiviral and cytostatic activity. Highly selective activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was noted for 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol 4b at a concentration of 0.07 microgram/mL. This activity must be dependent on a specific phosphorylation by the virus-encoded thymidine kinase (TK), since compound 4b was inactive against TK-deficient mutants of HSV-1. The corresponding cytosine 4c and guanine 4e analogues showed activity against HSV-1, HSV-2, and other herpes viruses (i.e. cytomegalovirus, varicella-zoster virus) at concentrations well below the cytotoxicity threshold (2 and 20 micrograms/mL, respectively). At these concentrations, compounds 4c and 4e proved also inhibitory to the growth of human T-cells (i.e. MT-4, CEM, MOLT-4).
Stevioside (250 mg capsules) was given three times daily to 10 healthy subjects. Steviol glucuronide (steviol 19-O-beta-D-glucopyranosiduronic acid; MM, 494.58; melting point, 198-199 degrees C) was characterized in the 24 h urine as the only excretion product of oral stevioside by MS, NMR, IR, and UV spectroscopy. This is the first report on the unambiguous identification of steviol glucuronide in human urine.
Fluorescence upconversion experiments were performed on monomer solutions of a number of structurally similar thiacarbocyanine dyes. The results from these time-resolved experiments combined with the data obtained from steady-state absorption and emission and 1 H NMR spectra allowed us to assign the components with different decay times to distinct isomers of the thiacarbocyanine dye molecules. Furthermore, it was possible to relate the substitution pattern of the dye molecules to their photophysical properties. For all mesosubstituted dyes, a short-lived component of either 3.5 or 5.7 ps could be assigned to a mono-cis conformation of the thiacarbocyanines. This component emits at longer wavelengths. A second component ranging from 15 to 71 ps and emitting at shorter wavelengths was attributed to the all-trans conformation of the mesosubstituted trimethine dyes. Time-resolved emission spectra revealed in a very clear and direct way the evolution of the contribution of the two conformations to the spectra. The size and/or solvation of the N,N′-substituents have a parallel influence on the decay time of the fast and the slow decaying component. Besides the N,N′-substituents also the meso-substituent has an influence on the decay time and amplitude of the longer-lived component.
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