Synthesis of (+)-Conagenin

An efficient total synthesis of (+)-conagenin was achieved. The right fragment of conagenin, alpha-methylserine containing a quaternary stereocenter attached to nitrogen, was synthesized using allyl cyanate-to-isocyanate rearrangement. The left fragment, 2,4-dihydroxy-3-methylpentanoic acid, has three contiguous stereogenic centers, which was efficiently constructed by enantioselective monoreduction of 2-alkyl-1,3-diketones reported by Cossy, and chelation-controlled stereoselective reduction of beta-hydroxy ketone. These two fragments were coupled through intramolecular amide bond formation with high efficiency.