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Starting from the optically pure [6]helicene-like alcohol (P,3S)-3-methyl-4-(4-methylphenyl)-1, 3,6,7-tetrahydrobenzo-[c]benzo [5,6]phenanthro [4,3-e]oxepin-14-ol, four helical phosphites were prepared from the corresponding chlorophosphites. These ligands containing parent or substituted 1,3,2-dioxaphospholan-2-yl or dibenzo [d,f][1,3,2]dioxaphosphepin-6-yl moieties were applied to the asymmetric hydroformylation of terminal alkenes catalyzed by Rh(acac)(CO) 2 and the asymmetric allylic amination of cinnamyl-type carbonates catalyzed by [Ir(cod)Cl] 2 . The helical phosphite containing the dibenzo [d,f][1,3,2]dioxaphosphepin-6-yl group was most successful in the asymmetric hydroformylation of

Supercritical carbon dioxide (scCO2) acts simultaneously as solvent and temporary protecting group during homogeneously rhodium-catalyzed hydroaminomethylation of ethyl methallylic amine. Cyclic amines are formed as the major products in scCO,, whereas the cyclic amide is formed preferentially in conventional solvents. Multinuclear high-pressure NMR spectroscopy revealed that this selectivity switch is mainly due to reversible formation of the carbamic acid in the solvent CO2, which reduces the tendency for intramolecular ring closure at the Rh-acyl intermediate. These results substantiate the general concept of using scCO2 as a protective medium for amines in homogeneous catalysis and demonstrate for the first time its application for selectivity control.

[reaction: see text] The sequence of hydroformylation and Fischer indole synthesis starting from amino olefins and aryl hydrazines is described. In a convergent manner, the two units bearing pharmacologically relevant substituents are assembled in the final indolization step. This modular and diversity-oriented approach to tryptamines and homotryptamines can be conducted in water and allows synthesis of branched and nonbranched tryptamines as well as tryptamine-based pharmaceuticals such as the 5-HT1D agonist L 775 606.

Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4' ') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg.kg-1.day-1, and 2/5 mice at 50 mg.kg-1.day-1, showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO* radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO* radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.

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