Methylene blue antimalarial

Scheme 6.268 shows the synthesis of the antimalarial drug artemisinin (564) from dihydroartemisinic acid (565) photooxygenation of 565 in the presence of Methylene Blue gives 566, which is oxidized by ground-state oxygen in 30% chemical yield.1462... 

Farber, P. M., Arscott, L. D., Williams, C. H., Jr., Becker, K., and Schirmer, R. H. (1998). Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 422,311-314. 

The earlier hypothesis put forward by Ehrlich that methylene blue exerts antimalarial activity paved the way for the discovery of a number of acridine analogues. The 9-aminoacridine analogues, however, are found to be extremely toxic in nature and, therefore, they have been successfully replaced by the 4-aminoquinoline analogues to a great extent. A few typical examples of this category are discussed below ... 

Ehrlich s hypothesis that methylene blue exerts antimalarial aetivity led to the diseovery of Mepacrine Mesylate. Describe its synthesis sequentially. 

Schulemann et aLy 1932), and mepacrine (6.9) ( Atebrin ) (Kikuth, 1932 Mauss and Mietzsch, I933)- They were inspired by the weak antimalarial action that Guttmann and Ehrlich (1891) had found in methylene blue (6.70), but systematic work had to await discovery of a test object, and Roehl found this in malaria-infected finches. 

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