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DOI: 10.1055/s-2005-865358
Radical-Mediated Synthesis of Racemic Deoxypodophyllotoxin and Related Lignans
Publikationsverlauf
Publikationsdatum:
02. Mai 2005 (online)
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Abstract
An approach for the synthesis of lignans related to the podophyllotoxin family is reported. The key reaction is a highly diastereoselective iodoacetal cyclization under iodine atom transfer conditions followed by a homolytic aromatic substitution. The second aromatic ring is introduced at a later stage via addition of aryllithium to an aryl ketone. A novel and very mild method for the deoxygenation of the intermediate tertiary benzylic alcohols is described.
Key words
radicals - iodoacetals - lignans - podophyllotoxin - deoxygenation - benzylic alcohols
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Imbert TF. Biochimie 1998, 80: 207 - 2
Damayanthi Y.Lown JW. Curr. Med. Chem. 1998, 5: 205 - 3
Hartwell JL. J. Am. Chem. Soc. 1947, 69: 2918 - 4
Hartwell JL.Schrecker AW. J. Am. Chem. Soc. 1951, 73: 2909 - 5
Schrecker AW.Hartwell JL. J. Org. Chem. 1956, 21: 381 - 6
Schrecker AW.Hartwell JL. J. Am. Chem. Soc. 1953, 75: 5916 - 7
Kuhn M.von Wartburg A. Helv. Chim. Acta 1967, 50: 1546 - 8
Jardine I. Med. Chem. 1980, 16: 319 - 9
Canel C.Moraes RM.Dayan FE.Ferreira D. Phytochemistry 2000, 54: 115 - 10
Meresse P.Dechaux E.Monneret C.Bertounesque E. Curr. Med. Chem. 2004, 11: 2443 - 11
Winograd B.Vermorken JB.Van Maanen J.Pinedo HM. Pharm. Weekbl. 1984, 119: 1277 - 12
Longstaff E.von Krogh G. Regul. Toxicol. Pharmacol. 2001, 33: 117 - 13
Desbene S.Giorgi-Renault S. Curr. Med. Chem. 2002, 2: 71 - 14
Masuda T.Oyama Y.Yonemori S.Takeda Y.Yamazaki Y.Mizuguchi S.Nakata M.Tanaka T.Chikahisa L.Inaba Y.Okada Y. Phytotherapy Res. 2002, 16: 353 - 15
Kupchan SM.Hemingway RJ.Hemingway NC. J. Pharm. Sci. 1967, 56: 408 - 16
Hokanson GC. J. Nat. Prod. 1979, 42: 378 - 17
Provan GJ.Waterman PG. Planta Medica 1985, 271 - 18
Sheriha GM.Abouamer K.Elshtaiwi BZ.Ashour AS.Abed FA.Alhallaq HH. Phytochemistry 1987, 26: 3339 - 19
Gözler B.Gözler T.Saglam H.Hesse M. Phytochemistry 1996, 42: 689 - 20
Bogucki DE.Charlton JL. J. Org. Chem. 1995, 60: 588 - 21
Morimoto T.Chiba M.Achiwa K. Tetrahedron Lett. 1990, 31: 261 - 22
Jones DW.Thompson AM. J. Chem. Soc., Chem. Commun. 1988, 1095 - 23
Robin JP.Dhal R.Brown E. Tetrahedron 1982, 38: 3667 - 24
Pelter A.Ward RS.Pritchard MC.Key IT. J. Chem. Soc., Perkin Trans. 1 1988, 1615 - 25
Brown E.Daugan A. Tetrahedron 1989, 45: 141 - 26
Zee SH.Chou SY. J. Chin. Chem. Soc. 1992, 39: 449 ; Chem. Abstr. 1992, 118, 59490 - 27
Pelter A.Ward RS.Jones DM.Maddocks P. J. Chem. Soc., Perkin Trans. 1 1993, 2621 - 28
Itoh T.Chika J.Takagi Y.Nishiyama S. J. Org. Chem. 1993, 58: 5717 - 29
Planchenault D.Dhal R.Robin JP. Tetrahedron 1993, 49: 5823 - 30
Bode JW.Doyle MP.Protopopova MN.Zhou Q.-L. J. Org. Chem. 1996, 61: 9146 - 31
Hanessian S.Ninkovic S. Can. J. Chem. 1996, 74: 1880 - 32
Kanematsu K.Tsuruoka M.Takaoka Y.Sasaki T. Heterocycles 1991, 32: 859 - 33
Brown E.Thomas D.Robin JP. C. R. Acad. Sci., Ser. 2 1982, 295: 563 - 34
Salom-Roig XJ.Dénès F.Renaud P. Synlett 2004, 1903 - 35 For review articles, see:
Giese B.Kopping B.Göbel T.Dickhaut J.Thoma G.Kulicke KJ.Trach F. Org. React. 1996, 48: 301 - 36
Ollivier C.Bark T.Renaud P. Synthesis 2000, 1598 - 37
Villar F.Equey O.Kolly-Kovac T.Renaud P. Chem. Eur. J. 2003, 9: 1566 - 38
Corminboeuf O.Renaud P.Schiesser CH. Chem. Eur. J. 2003, 9: 1578 - 39
Miranda LD.Zard SZ. Org. Lett. 2002, 4: 1135 - 41
Seebach D.Bossler H.Gründler H.Shoda S.Wenger R. Helv. Chim. Acta 1991, 74: 197 - 42
Zard SZ. In Radicals in Organic Synthesis Vol. 1:Renaud P.Sibi MP. Wiley-VCH; Weinheim: 2001. p.90 - 43
Kazuhiko K.Masaru O.Kozawa MYM.Hiroshi T.Kikiye B.Yoshihiko I. Agric. Biolog. Chem. 1989, 53: 777 - 44
Villar F.Renaud P. Tetrahedron Lett. 1998, 39: 8655 - 45
Villar F.Equey O.Renaud P. Org. Lett. 2000, 2: 1061 - 46
Nouguier R.Gastaldi S.Stien D.Bertrand M.Villar F.Andrey O.Renaud P. Tetrahedron: Asymmetry 2003, 14: 3005 - 47
Pericas MA.Serratosa F.Valenti E. Tetrahedron 1987, 43: 2311 - 48
Ulubelen A.Gil RR.Cordell GA.Mericli AH.Mericli F. Phytochemistry 1995, 39: 417
References
The enol ether (E)-8 was prepared via Heck coupling of the piperonyloyl chloride(6) and ethyl vinyl ether, however, this reaction is low yielding. Iodoacetalization of (E)-8 with allyl alcohol and NIS afforded the diastereomer of iodoacetal 9. This approach was abandoned due to the low yield of the Heck coupling process.