合成路线1

B) Synthesis of intermediate (XIV): Palladium-catalyzed coupling of 1-pentyn-4-ol (VIII) with 3-bromopyridine (IX) afforded the pyridinealkynol (X), which was then subjected to sequential hydrogenation and Swern oxidation followed by reductive amination of the intermediate ketone (XI) with sodium cyanoborohyride to afford the racemic amine (XII). Resolution was achieved through fractional crystallization of the corresponding diastereoisomeric (R)-mandelamides that had been obtained by acylation of the racemic amine with (R)-mandelic acid in DMF in the presence of 1-hydroxybenzotriazole and dicyclohexylcarbodiimide. Acid-catalyzed hydrolysis of the diastereoisomerically pure (R,R)-mandelamide (XII) provided the resolved (R)-alpha-methyl-3-pyridinebutanamine (XIV). C) Synthesis of Ro-24-0238: Stereochemical assignment was based on a single crystal X-ray analysis of the intermediate mandelamide. Reaction of the chiral amine with the activated ester of (E,E)-5-(4-methoxyphenyl)-2,4-decadienoic acid gave Ro 24-0238. Stereochemical assignment was based on a single crystal X-ray analysis of the intermediate mandelamide. Reaction of the chiral amine with the activated ester of (E,E)-5-(4-methoxyphenyl)-2,4-decadienoic acid gave Ro 24-0238.