title: Total Syntheses of (+)-Grandilodine C and (+)-Lapidilectine B and Determination of their Absolute Stereochemistry.
abstract: Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium-catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.|Molecular Chirality Research Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan. anishida@faculty.chiba-u.jp.|Molecular Chirality Research Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan. anishida@faculty.chiba-u.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
keywords: alkaloids; fused-ring system; heterocycles; natural products; total synthesis