title: Enantioselective formal synthesis of (-)-podophyllotoxin from (2S,3R)-3-arylaziridine-2-carboxylate.
abstract: Meyers' 4-aryl-1-tetralone-lactone and ent-Zhang's 2-diarylmethyl-4-oxobutanoate were synthesized in the formal synthesis of (-)-podophyllotoxin from (2S,3R)-3-arylaziridine-2-carboxylate, via 3,3-diarylpropanoate as a common intermediate, in an overall 42% yield through 10 steps and 31% yield through 6 steps, respectively. The key steps in the synthesis were regio- and diastereoselective ring opening with an aromatic nucleophile, samarium iodide promoted reductive C-N bond cleavage, and Stille coupling for introducing the vinyl functionality. The starting aziridine was enantioselectively prepared from 3,4,5-trimethoxybenzaldehyde by guanidinium ylide mediated asymmetric aziridination. All nitrogen components used in the reaction sequence are reusable as the starting guanidinium source.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, Chiba, 260-8675, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D001388:Aziridines / Q000737:chemistry*; D008968:Molecular Conformation; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001388:Aziridines; C073440:aziridine-2-carboxylic acid; D011034:Podophyllotoxin