Phosphinates antimalarial

P-Blockers, benzodiazepines, NSAIDs, barbiturates NSAIDs, protease inhibitors, P-blockers, benzodiazepines Antimalarials, NSAIDs, P-blockers, bronchodilators Phosphine oxides, NSAIDs, anticonvulsants Bronchodilators, P-blockers... 

Known bicyclo[4.3.1]enone 15758 was converted into vinylsilane 158 with bis(trimethylsilyl)methyl lithium.55 Diene 158 underwent selective ozonolysis at the cis-olefin under conditions to produce differentially oxidized termini 90 alde-hydo-ester 159 was homologated with a phosphine oxide anion91 to enol 160. Subsequent hydrolysis of 161 provided substrate 162, which after tandem ozonolysis-acidification gave racemic 6,9-desmethyl analogue 155. Unfortunately, initial efforts failed to resolve 155 into its two optical isomers with cellulose triacetate.92 However, the antimalarial activity of racemate 155 is intriguing, as discussed in a later section. 

Other chiral phosphine/transition metal complexes catalyze the hydrogenation of a-pyridyl ketones (to biologicaly active amino alcohols like (/ ,S)-Mefloquine, an antimalarial agent (Hoffmann-La Roche [30]) or of a-benzamide ketones to... 

The human malaria parasite Plasmodium falciparum expresses two neutral zinc-aminopeptidases, PfA-Ml and PfA-M17, which function in regulating the intracellular pool of amino acids required for parasite growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. As a result of the rapid emergence of drug-resistant parasites, blocking these peptidases with potent inhibitors has been proposed as a potential new antimalarial therapy. The simple phosphinic dipeptide 61 (Table 1) was reported to inhibit PfA-M17 with a Ki value of 80 nM [130]. 

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