合成路线1

The synthesis of a deuterated analogue of artemether starting from the previously reported carboxylic acid (I) is shown in Scheme 14079601c. Alkylation of the dilithium derivative of (I) with CD3I gives the alpha-methyl acid (II) as a single stereoisomer. Ozonolysis of (II), followed by acid-catalyzed cyclization affords the deuterated artemisinin (III). Reduction of lactone (III) by means of DIBAL provides lactol (IV). Finally, the target ethyl ether is formed by treatment of (IV) with ethanol and boron trifluoride etherate (10).