Short and stereoselective total synthesis of furano lignans (+/-)-dihydrosesamin, (+/-)-lariciresinol dimethyl ether, (+/-)-acuminatin methyl ether, (+/-)-sanshodiol methyl ether, (+/-)-lariciresinol, (+/-)-acuminatin, and (+/-)-lariciresinol monomethyl ether and furofuran lignans (+/-)-sesamin, (+/-)-eudesmin, (+/-)-piperitol methyl ether, (+/-)-pinoresinol, (+/-)-piperitol, and (+/-)-pinoresinol monomethyl ether by radical cyclization of epoxides using a transition-metal radical source.
Intramolecular radical cyclization of suitably substituted epoxy ethers 4a-g using bis(cyclopentadienyl)titanium(III) chloride as the radical source resulted in trisubstituted tetrahydrofurano lignans and 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignans depending on the reaction conditions. The titanium(III) species was prepared in situ from commercially available titanocene dichloride and activated zinc dust in THF. Upon radical cyclization followed by acidic workup, epoxy olefinic ethers 4a-g afforded furano lignans dihydrosesamin 1a, lariciresinol dimethyl ether 1b, acuminatin methyl ether 1e, and sanshodiol methyl ether 1g directly and lariciresinol 1h, acuminatin 1i, and lariciresinol monomethyl ether 1j after removal of the benzyl protecting group by controlled hydrogenolysis of the corresponding cyclized products. The furofuran lignans sesamin 2a, eudesmin 2b, and piperitol methyl ether 2e were also prepared directly by using the same precursors 4a-f on radical cyclization followed by treatment with iodine and pinoresinol 2h, piperitol 2i, and pinoresinol monomethyl ether 2j after controlled hydrogenolysis of the benzyl protecting group of the corresponding cyclized products. Two naturally occurring acyclic lignans, secoisolariciresinol 5h and secoisolariciresinol dimethyl ether 5b, have also been prepared by exhaustive hydrogenolysis of 2h and 2b, respectively.
Roy
Subhas Chandra
SC
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India. ocsr@mahendra.iacs.res.in
Rana
Kalyan Kumar
KK
Guin
Chandrani
C
D000478:Alkylation; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D004149:Dioxoles / Q000138:chemical synthesis; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D004988:Ethers, Cyclic / Q000138:chemical synthesis*; D005419:Flavonoids / Q000138:chemical synthesis; D005663:Furans / Q000138:chemical synthesis*; D006027:Glycosides / Q000138:chemical synthesis; D017705:Lignans / Q000138:chemical synthesis*; D008031:Lignin / Q000138:chemical synthesis; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
D004149:Dioxoles; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005419:Flavonoids; D005663:Furans; D006027:Glycosides; D017705:Lignans; C077860:acuminatin; C105875:eudesmin; C060282:lariciresinol; D008031:Lignin; C054125:sesamin; C103298:pinoresinol