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2-Hydroxydodecyl starch ethers were synthesized by reaction of 1,2-epoxydodecane with potato starch in aqueous alkaline medium. Careful attention has been given to the purification steps and more precisely to the identification and quantification of the impurities. The purification by Soxhlet extraction compared to the process by grinding required fewer steps but a longer time. The values of the MS were always around 1.1, but the recovery yields were higher for the treatment by grinding compared to Soxhlet (85 vs 63%).

The effect of a 2,5Bboat conformation on xyloside reactivity has been investigated by studying the hydrolysis and glycosylation of a series of synthetic xyloside analogues based on a 2‐oxabicyclo[2.2.2]octane framework, which forces the xylose analogue to adopt a 2,5Bconformation. The locked β‐xylosides were found to hydrolyze 100–1200 times faster than methyl β‐D‐xylopyranoside, whereas the locked α‐xylosides hydrolyzed up to 2×104times faster than methyl α‐D‐xylopyranoside. A significant rate enhancement was also observed for the glycosylation reaction. The high reactivity of these conformers can be related to the imposition of a 2,5Bconformation, which approximates a transition state (TS) boat conformation. In this way, the energy penalty required to go from the chair to the TS conformation is already paid. These results parallel and support the observation that the GH‐11 xylanase family force their substrate to adopt a 2,5Bconformation to achieve highly efficient enzymatic glycosidic bond hydrolysis.

Activated 1,2-glycerol carbonate has been subjected to nucleophilic substitution with oxygen-, nitrogen- and sulfur nucleophiles. Selective reactions with thiol derivatives have been especially investigated for the preparation of mono- and dithiofunctionalized 3-carbon synthons.

α‐ and β‐Cyclodextrin 6A,6D‐diacids (1and 2), β‐cyclodextrin‐6‐monoacid (14), β‐cyclodextrin 6A,6D‐di‐O‐sulfate (16) and β‐cyclodextrin‐6‐heptasulfate (19) were synthesised. Acids 1, 2and 14were made from perbenzylated α‐ or β‐cyclodextrin, by diisobutylaluminum hydride (DIBAL)‐promoted debenzylation, oxidation and deprotection. Addition of molecular sieves was found to improve the debenzylation reaction. Sulfates 16and 19were made by sulfation of the appropriately partially protected derivatives and deprotection. Catalysis of 4‐nitrophenyl glycoside cleavage by these cyclodextrin derivatives was studied. Compounds 1, 2and 16were found to catalyse the reaction, with the catalysis following Michaelis–Menten kinetics and depending first order on the phosphate concentration. In a phosphate buffer (0.5 M, 59 °C, pH 8.0), KMvaried from 2–10 mMand the kcat/kuncatratio from 80–1000 depending on the stereochemistry of the substrate and the catalyst, with 2being the best catalyst and with the sulfated 16also displaying catalytic ability. The monoacid 14and the heptasulfate 19were not catalytic.

Four cyclodextrin ketones were synthesised and investigated as epoxidation catalysts. In the presence of oxone they catalysed the epoxidation of mono-, di- and trisubstituted alkenes in 17–100 % yield and 0–45 % ee. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

ABSTRACTThe protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome P450 3A4, which boosts the activities of coadministered PIs, resulting in augmented plasma PI levels, simplification of the dosage regimen, and better efficacy against resistant viruses. The objectives of the present open-label, multiple-dose study were to determine the steady-state pharmacokinetics of amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at 100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated with different antiretroviral combinations including or not including a nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients completed the study. The steady-state mean minimum plasma amprenavir concentration (Cmin,ss) was 1.92 μg/ml for patients who received amprenavir and ritonavir without an NNRTI and 1.36 μg/ml for patients who received amprenavir and ritonavir plus efavirenz. For patients who received amprenavir-ritonavir without an NNRTI, the steady-state mean peak plasma amprenavir concentration (Cmax,ss) was 7.12 μg/ml, the area under the concentration-time curve from 0 to 10 h (AUC0-10) was 32.06 μg · h/ml, and the area under the concentration-time curve over a dosing interval (12 h) at steady-state (AUCss) was 35.74 μg · h/ml. Decreases in the mean values of Cmin,ss(29%), Cmax,ss(42%), AUC0-10(42%), and AUCss(40%) for amprenavir occurred when efavirenz was coadministered with amprenavir-ritonavir. No unexpected side effects were observed. As expected, coadministration of amprenavir with ritonavir resulted in an amprenavir Cmin,ssmarkedly higher than those previously reported for the marketed dose of amprenavir. When amprenavir-ritonavir was coadministered with efavirenz, amprenavir-ritonavir maintained a mean amprenavir Cmin,ssabove the mean 50% inhibitory concentration of amprenavir previously determined for both wild-type HIV-1 isolates and HIV-1 strains isolated from PI-experienced patients. These data support the use of low-dose ritonavir to enhance the level of exposure to amprenavir and increase the efficacy of amprenavir.

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.