Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 46

Anti‐Infective Medicines/Antiprotozoal Medicines/Antimalarial Medicines/For Curative Treatment

A single‐enantiomer molecule with multiple chiral carbons is often formed by modification of a natural product which has most or all of the chiral carbons already in place.

Discussion. Artesunate is semisynthetic, and it is manufactured in two steps from artemisinin. The ester is formed by reaction of the hemiacetal (dihydroartemisinin) with succinic anhydride. The hemiacetal of dihydroartemisinin is formed by reduction of the ester of artemisinin. Artemisinin is a natural product isolated from the plant A. annua or sweet wormwood.

Artemisinin is also manufactured in four steps from artemisinic acid. In the last step, a hydroperoxide is formed by α‐oxidation of an aldehyde with triplet oxygen. The aldehyde, hydroperoxide, ketone, and carboxylic acid then assemble to form artemisinin. The aldehyde and ketone are formed by cleavage of an allylic hydroperoxide (Hock Rearrangement). The allylic hydroperoxide is formed from the alkene (Ene Reaction). The alkene, dihydroartemisinic acid, is formed by reduction of artemisinic acid. Artemisinic acid is a natural product also isolated from the plant A. annua or sweet wormwood. Artemisinic acid is also produced by fermentation.