Significantly better yields were achieved in Mizoroki-Heck reactions using 4-phenoldiazonium salts instead of their O-alkylated analogues under otherwise identical conditions. We found that a oneflask deacetylation-diazotation-precipitation sequence starting from paracetamol or acetanilides derived thereof provides a convenient access to the required diazonium tetrafluoroborates. The utility of these arylating agents in palladium-catalyzed C À C bond forming reactions was demonstrated for a oneflask-synthesis of the heterocyclic core of the drug aripiprazole. Notably, the diazonium salt formation from an acetanilide could be combined with two Pdcatalyzed steps in a one-flask sequence, without any exchange of solvents or isolation of intermediates.

Bis-cycloSal-d4T-monophosphates have been synthesized as potentially anti-HIV active "dimeric" prodrugs of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (d4TMP). These pronucleotides display a mask-drug ratio of 1:2, a novelty in the field of pronucleotides. Both bis-cycloSal-d4TMP 6 and bis-5-methyl-cycloSal-d4TMP 7 showed increased hydrolytic stability as compared to their "monomeric" counterparts and a completely selective hydrolytic release of d4TMP. The hydrolysis pathway was investigated via 31P NMR spectroscopy. Moreover, due to the steric bulkiness, compound 6 already displayed strongly reduced inhibitor potency toward human butyrylcholinesterase (BChE), while compound 7 turned out to be devoid of any inhibitory activity against BChE. Partial separation of the diastereomeric mixture of 6 revealed strong dependence of the pronucleotides' properties on the stereochemistry at the phosphorus centers. Both 6 and 7 showed good activity against HIV-1 and HIV-2 in wild-type CEM cells in vitro. These compounds were significantly more potent than the parent nucleoside d4T 1 in HIV-2-infected TK-deficient CEM cells, indicating an efficient TK-bypass.

Diurnal plasma lipids and lipoproteins were studied in twelve healthy young males on corn oil and palm oil diets, respectively. The major triglyceridy. Lecithin-cholesterol acyl transferase, lipoprotein lipase and hepatic triglyceride lipase were also measured. diurnal changes of triglycerides and cholesterol were confined to lipoproteins of d less than 1.006 kg/l. There was a diurnal rise of lecithin-cholesterol acyl transferase activity with corn oil but not with palm oil. Fasting and postprandial postheparin lipoprotein lipase and hepatic triglyceride lipase were similar but there was a significant correlation of postprandial hepatic lipase with postprandial plasma triglycerides on palm oil. Marked diurnal changes of triglyceride fatty acids were observed not only in 'very low density lipoprotein' but also in high-density lipoprotein amounting to approximately one third of total high density lipoprotein triglyceride fatty acids.

New divergent approaches to 2′,3′‐modified carbocyclic L‐nucleoside analogues starting from enantiomerically pure (1R,2S)‐ or (1S,2R)‐2‐(benzyloxymethyl)cyclopent‐3‐enol are described. In the key step, stereochemically pure cyclopentanols were condensed with N3‐protected thymine through a modified Mitsunobu protocol. Moreover, several routes to different cyclopentanol derivatives, to prepare carbocyclic L‐2′,3′‐didehydro‐2′,3′‐dideoxynucleosides (L‐d4N), L‐2′,3′‐dideoxynucleosides (L‐ddN), and L‐ribonucleosides are reported.