Radical-Mediated Synthesis of Racemic Deoxypodophyllotoxin and Related Lignans

Tanja Kolly-Kovač; Philippe Renaud

doi:10.1055/s-2005-865358

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Synthesis 2005(9): 1459-1466
DOI: 10.1055/s-2005-865358

PAPER

Radical-Mediated Synthesis of Racemic Deoxypodophyllotoxin and Related Lignans

Tanja Kolly-Kovač, Philippe Renaud*
Universität Bern, Departement für Chemie und Biochemie, Freiestrasse 3, 3012 Bern, Switzerland
Fax: +41(31)6314359; e-Mail: philippe.renaud@ioc.unibe.ch;

Further Information

Publication History

Received 11 April 2005
Publication Date:
02 May 2005 (online)

Abstract
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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

References

1 Imbert TF. Biochimie 1998, 80: 207

Crossref Google Scholar
2 Damayanthi Y. Lown JW. Curr. Med. Chem. 1998, 5: 205

PubMed Google Scholar
3 Hartwell JL. J. Am. Chem. Soc. 1947, 69: 2918

Google Scholar
4 Hartwell JL. Schrecker AW. J. Am. Chem. Soc. 1951, 73: 2909

Google Scholar
5 Schrecker AW. Hartwell JL. J. Org. Chem. 1956, 21: 381

Google Scholar
6 Schrecker AW. Hartwell JL. J. Am. Chem. Soc. 1953, 75: 5916

Crossref Google Scholar
7 Kuhn M. von Wartburg A. Helv. Chim. Acta 1967, 50: 1546

Crossref Google Scholar
8 Jardine I. Med. Chem. 1980, 16: 319

Google Scholar
9 Canel C. Moraes RM. Dayan FE. Ferreira D. Phytochemistry 2000, 54: 115

Crossref Google Scholar
10 Meresse P. Dechaux E. Monneret C. Bertounesque E. Curr. Med. Chem. 2004, 11: 2443

Crossref Google Scholar
11 Winograd B. Vermorken JB. Van Maanen J. Pinedo HM. Pharm. Weekbl. 1984, 119: 1277

Google Scholar
12 Longstaff E. von Krogh G. Regul. Toxicol. Pharmacol. 2001, 33: 117

Crossref Google Scholar
13 Desbene S. Giorgi-Renault S. Curr. Med. Chem. 2002, 2: 71

Google Scholar
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

Crossref Google Scholar
15 Kupchan SM. Hemingway RJ. Hemingway NC. J. Pharm. Sci. 1967, 56: 408

Crossref Google Scholar
16 Hokanson GC. J. Nat. Prod. 1979, 42: 378

Crossref Google Scholar
17 Provan GJ. Waterman PG. Planta Medica 1985, 271

Google Scholar
18 Sheriha GM. Abouamer K. Elshtaiwi BZ. Ashour AS. Abed FA. Alhallaq HH. Phytochemistry 1987, 26: 3339

Crossref Google Scholar
19 Gözler B. Gözler T. Saglam H. Hesse M. Phytochemistry 1996, 42: 689

Crossref Google Scholar
20 Bogucki DE. Charlton JL. J. Org. Chem. 1995, 60: 588

Google Scholar
21 Morimoto T. Chiba M. Achiwa K. Tetrahedron Lett. 1990, 31: 261

Crossref Google Scholar
22 Jones DW. Thompson AM. J. Chem. Soc., Chem. Commun. 1988, 1095

Crossref Google Scholar
23 Robin JP. Dhal R. Brown E. Tetrahedron 1982, 38: 3667

Crossref Google Scholar
24 Pelter A. Ward RS. Pritchard MC. Key IT. J. Chem. Soc., Perkin Trans. 1 1988, 1615

Crossref Google Scholar
25 Brown E. Daugan A. Tetrahedron 1989, 45: 141

Crossref Google Scholar
26 Zee SH. Chou SY. J. Chin. Chem. Soc. 1992, 39: 449 ; Chem. Abstr. 1992, 118, 59490

Crossref Google Scholar
27 Pelter A. Ward RS. Jones DM. Maddocks P. J. Chem. Soc., Perkin Trans. 1 1993, 2621

Crossref Google Scholar
28 Itoh T. Chika J. Takagi Y. Nishiyama S. J. Org. Chem. 1993, 58: 5717

Crossref Google Scholar
29 Planchenault D. Dhal R. Robin JP. Tetrahedron 1993, 49: 5823

Crossref Google Scholar
30 Bode JW. Doyle MP. Protopopova MN. Zhou Q.-L. J. Org. Chem. 1996, 61: 9146

Crossref Google Scholar
31 Hanessian S. Ninkovic S. Can. J. Chem. 1996, 74: 1880

Crossref Google Scholar
32 Kanematsu K. Tsuruoka M. Takaoka Y. Sasaki T. Heterocycles 1991, 32: 859

Crossref Google Scholar
33 Brown E. Thomas D. Robin JP. C. R. Acad. Sci., Ser. 2 1982, 295: 563

Google Scholar
34 Salom-Roig XJ. Dénès F. Renaud P. Synlett 2004, 1903

Google Scholar
35 For review articles, see: Giese B. Kopping B. Göbel T. Dickhaut J. Thoma G. Kulicke KJ. Trach F. Org. React. 1996, 48: 301

Google Scholar
36 Ollivier C. Bark T. Renaud P. Synthesis 2000, 1598

Article in Thieme Connect Google Scholar
37 Villar F. Equey O. Kolly-Kovac T. Renaud P. Chem. Eur. J. 2003, 9: 1566

Google Scholar
38 Corminboeuf O. Renaud P. Schiesser CH. Chem. Eur. J. 2003, 9: 1578

Google Scholar
39 Miranda LD. Zard SZ. Org. Lett. 2002, 4: 1135

Crossref Google Scholar
41 Seebach D. Bossler H. Gründler H. Shoda S. Wenger R. Helv. Chim. Acta 1991, 74: 197

Crossref Google Scholar
42 Zard SZ. In Radicals in Organic Synthesis Vol. 1: Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001. p.90

Google Scholar
43 Kazuhiko K. Masaru O. Kozawa MYM. Hiroshi T. Kikiye B. Yoshihiko I. Agric. Biolog. Chem. 1989, 53: 777

Google Scholar
44 Villar F. Renaud P. Tetrahedron Lett. 1998, 39: 8655

Crossref Google Scholar
45 Villar F. Equey O. Renaud P. Org. Lett. 2000, 2: 1061

Crossref Google Scholar
46 Nouguier R. Gastaldi S. Stien D. Bertrand M. Villar F. Andrey O. Renaud P. Tetrahedron: Asymmetry 2003, 14: 3005

Crossref Google Scholar
47 Pericas MA. Serratosa F. Valenti E. Tetrahedron 1987, 43: 2311

Crossref Google Scholar
48 Ulubelen A. Gil RR. Cordell GA. Mericli AH. Mericli F. Phytochemistry 1995, 39: 417

Crossref Google Scholar

40

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.