Anti-malarial reagents

Synthesis of anti-malarial reagent enpiroline (17) involved the formation of the pyridine skeleton 206 via the Krdhnke reaction of aroyl acrylic acid 204, acyl pyridinium salt 205, and ammonia acetate. Condensation of the carboxyl group in 206 with 2-lithiopyridine afforded the diaryl ketone 207. The relative higher basicity of the terminal pyridinyl ring allowed selective reduction of this ring via hydrogenation in the presence of an acid and simultaneously reduction of the ketone to the alcohol. The desired isomer was then obtained by fractional crystallization to afford 17. ... 

Quinine, n natural anti-malarial, is commonly used as an optically active reagent to resolve acidic enantiomers. How many chiral carbons exist in the quinine molecule drawn below ... 

These nitrogen-containing natural products, often with powerful biological properties, are not usually incorporated into target molecules. However, they are important in asymmetric syntheses as the foundations of many reagents and catalysts. Quinine 119 is familiar as an anti-malarial and an ingredient in tonic water. Quinine and its twin cinchona alkaloid quinidine 118 are referred to as pseudo enantiomers. Each occurs naturally as one enantiomer only but the two structures are nearly enantiomeric only the vinyl side-chains disturb the symmetry and they act as enantiomers. The vinyl side-chains are reduced and two molecules of, say, dihydroquinine (DHQ) are joined... 

One of the most widely used supported reagents for reduction is polymer-supported borohydride. An interesting example is the final step of the total synthesis of polysphorin 55, an anti-malarial natural product (Scheme 4.15) [62]. The stereoselective reduction of ketone 54 occurred with excellent diastereomeric excess when PS-BEMP was used, affording the 55 in 90% yield. 

Lee, A.-L. and Ley, S.V. (2003) The synthesis of the anti-malarial natural product polysphorin and analogues using polymer-supported reagents and scavengers. Organic and Biomolecular Chemistry, 1, 3957-3966. 

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