title: Free-radical-mediated conjugate additions. Enantioselective synthesis of butyrolactone natural products: (-)-enterolactone, (-)-arctigenin, (-)-isoarctigenin, (-)-nephrosteranic acid, and (-)-roccellaric acid.
abstract: Lewis acid-mediated conjugate addition of alkyl radicals to a differentially protected fumarate 10 produced the monoalkylated succinates with high chemical efficiency and excellent stereoselectivity. A subsequent alkylation or an aldol reaction furnished the disubstituted succinates with syn configuration. The chiral auxiliary, 4-diphenylmethyl-2-oxazolidinone, controlled the stereoselectivity in both steps. Manipulation of the disubstituted succinates obtained by alkylation furnished the natural products (-)-enterolactone, (-)-arctigenin, and (-)-isoarctigenin. The overall yields for the target natural products were 20-26% over six steps. Selective functionalization of the disubstituted succinates obtained by aldol condensation gave the paraconic acid natural products (-)-nephrosteranic acid (8) and (-)-roccellaric acid (9). The overall yield of the natural products 8 and 9 over four steps was 53% and 42%, respectively.
authors.affiliation: Department of Chemistry, North Dakota State University, Fargo, North Dakota 58105-5516, USA. Mukund.Sibi@ndsu.nodak.edu
authors.forename: Mukund P
authors.initials: MP
authors.lastname: Sibi
authors.forename: Pingrong
authors.initials: P
authors.lastname: Liu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Ji
authors.forename: Saumen
authors.initials: S
authors.lastname: Hajra
authors.forename: Jian-xie
authors.initials: JX
authors.lastname: Chen
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000478:Alkylation; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D005609:Free Radicals / Q000737:chemistry*; D005650:Fumarates / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D013386:Succinates / Q000737:chemistry
chemical_list: D001688:Biological Products; D005609:Free Radicals; D005650:Fumarates; D005663:Furans; D007783:Lactones; D017705:Lignans; D013386:Succinates; C456479:isoarctigenin; C456480:nephrosteranic acid; C428504:roccellaric acid; D015107:4-Butyrolactone; C071942:arctigenin; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone