Stereoselective Synthesis of the Pyrrolizidine Alkaloids (-)-Integerrimine and (+)-Usaramine

Article abstract of DOI:10.1021/jo00034a017

Two routes to the pyrrolizidine alkaloid (-)-integerrimine (1) are described.The first, starting from methyl (R)-(-)-3-hydroxy-2-methylpropionate, proceeded in 19 steps to integerrinecic acid lactone (5) which was transformed to the necic acid derivative 30.The latter was coupled to protected retronecine 31, and the synthesis of 1 was completed by lactonization employing Vedejs' protocol.A second, shorter synthesis of (-)-1 was accomplished via 5, starting from (R)-(+)-β-citronellol (36).This pathway invoked Katsuki-Sharpless epoxidation of 42 for stereoselective construction of the tertiary alcohol of integerrinecic acid.A parallel sequence proceeding via the stereoisomeric epoxide 44 led to the necic acid segment 75 of the alkaloid (+)-usaramine (2).This acid was coupled to the retronecine borane 82 and then lactonized to 2.