title: Total synthesis of (+/-)-scopadulin.
abstract: The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. A highly stereoselective cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the sterically hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols. Finally, the total synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16 and modification of the C-4 alpha-functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated methylation for the generation of a tertiary axial alcohol at C-16 is extremely high.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: S M
authors.initials: SM
authors.lastname: Rahman
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: N
authors.initials: N
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: D
authors.initials: D
authors.lastname: Patra
authors.forename: C
authors.initials: C
authors.lastname: Iwata
authors.forename: N
authors.initials: N
authors.lastname: Maezaki
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis; D004224:Diterpenes / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; C064856:scopadulin