title: Stereocontrolled total synthesis of polygalolide A.
abstract: The total synthesis of polygalolide A, a secondary metabolite that was isolated from a Chinese medicinal plant, is reported. A key issue in this synthesis was construction of an oxabicyclo[3.2.1] skeleton, which was solved by the development of an intramolecular Ferrier-type C-glycosylation of a glucal with siloxyfuran as an internal nucleophile. The substrate was prepared from D-glucal by the introduction of trimethylsilylacetylene and siloxyfuran groups. Although C-glycosylation did not occur under the conditions found from model experiments, further examination revealed that the combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,4,6-collidine successfully afforded the desired product as a single diastereomer. The siloxy group at the C3 position played a crucial role in the stereocontrol of this reaction. The product was further transformed into a tetracyclic compound as follows: The vinyl ether and acetylenic moieties were reduced and the siloxy group was removed with a Barton-McCombie reaction. The construction of the six-membered ether and the γ-lactone provided the tetracyclic compound. Finally, a phenolic moiety was introduced by using a Mukaiyama aldol reaction to furnish polygalolide A.
authors.affiliation: Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yamada
authors.forename: Masaatsu
authors.initials: M
authors.lastname: Adachi
authors.forename: Minoru
authors.initials: M
authors.lastname: Isobe
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikawa
mesh_terms: D000475:Alkenes / Q000737:chemistry; D018360:Crystallography, X-Ray; D006031:Glycosylation; D008968:Molecular Conformation; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D031801:Polygala / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D010636:Phenols; C476753:polygalolide A