Total Synthesis of 2′",5′"-Diepisilvestrol and Its C1′" Epimer: Key Structure Activity Relationships at C1′" and C2′"

被引：20

作者：

Chambers, Jennifer M. ^{[1
]}

Huang, David C. S. ^{[2
,3
]}

Lindqvist, Lisa M. ^{[2
,3
]}

Savage, G. Paul ^{[4
]}

White, Jonathan M. ^{[1
]}

Rizzacasa, Mark A. ^{[1
]}

机构：

[1] Univ Melbourne, Inst Bio21, Sch Chem, Melbourne, Vic 3010, Australia

[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia

[3] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

[4] CSIRO Mol & Hlth Technol, Melbourne, Vic 3168, Australia

来源：

JOURNAL OF NATURAL PRODUCTS | 2012年 / 75卷 / 08期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

SILVESTROL; (-)-EPISILVESTROL; DERIVATIVES;

D O I：

10.1021/np300376f

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

The first total synthesis of the low-abundance natural product 2''',5'''-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]-benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2''',5'''-diepisilvestrol (4) and its C1 epimer 1''',2''',5'''-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2''',5'''-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1''',2''',5'''-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1''' and C2'''. has a large effect on the biological activity.

引用

页码：1500 / 1504

页数：5

共 22 条

[1] Total Synthesis of the Potent Anticancer Aglaia Metabolites (-)-Silvestrol and (-)-Episilvestrol and the Active Analogue (-)-4′-Desmethoxyepisilvestrol [J].

Adams, Tim E. ;

El Sous, Mariana ;

Hawkins, Bill C. ;

Hirner, Sebastian ;

Holloway, Georgina ;

Khoo, Mui Ling ;

Owen, David J. ;

Savage, G. Paul ;

Scammells, Peter J. ;

Rizzacasa, Mark A. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (04) :1607-1616

[2] Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model [J].

Bordeleau, Marie-Eve ;

Robert, Francis ;

Gerard, Baudouin ;

Lindqvist, Lisa ;

Chen, Samuel M. H. ;

Wendel, Hans-Guido ;

Brem, Brigitte ;

Greger, Harald ;

Lowe, Scott W. ;

Porco, John A., Jr. ;

Pelletier, Jerry .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2651-2660

[3] Antitumor Activity and Mechanism of Action of the Cyclopenta[b]benzofuran, Silvestrol [J].

Cencic, Regina ;

Carrier, Marilyn ;

Galicia-Vazquez, Gabriela ;

Bordeleau, Marie-Eve ;

Sukarieh, Rami ;

Bourdeau, Annie ;

Brem, Brigitte ;

Teodoro, Jose G. ;

Greger, Harald ;

Tremblay, Michel L. ;

Porco, John A., Jr. ;

Pelletier, Jerry .

PLOS ONE, 2009, 4 (04)

[4] Biomimetic synthesis of the novel 1,4-dioxanyloxy fragment of silvestrol and episilvestrol [J].

El Sous, M ;

Rizzacasa, MA .

TETRAHEDRON LETTERS, 2005, 46 (02) :293-295

[5] Total synthesis of (-)-episilvestrol and (-)-silvestrol [J].

El Sous, Mariana ;

Khoo, Mui Ling ;

Holloway, Georgina ;

Owen, David ;

Scammells, Peter J. ;

Rizzacasa, Mark A. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (41) :7835-7838

[6] DIRECTED REDUCTION OF BETA-HYDROXY KETONES EMPLOYING TETRAMETHYLAMMONIUM TRIACETOXYBOROHYDRIDE [J].

EVANS, DA ;

CHAPMAN, KT ;

CARREIRA, EM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (11) :3560-3578

[7]

Farrugia L.J., 1997, J. Appl. Crystallogr., V30, P565, DOI [10.1107/S0021889897003117, DOI 10.1107/S0021889897003117]

[8]

Farrugia L. J., 1999, Journal of Applied Crystallography, V32, P837, DOI [DOI 10.1107/S0021889812029111, 10.1107/S0021889899006020, DOI 10.1107/S0021889899006020]

[9] A biomimetic approach to the rocaglamides employing photogeneration of oxidopyryliums derived from 3-hydroxyflavones [J].

Gerard, B ;

Jones, G ;

Porco, JA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (42) :13620-13621

[10] Enantioselective synthesis of the complex rocaglate (-)-silvestrol [J].

Gerard, Baudouin ;

Cencic, Regina ;

Pelletier, Jerry ;

Porco, John A., Jr. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (41) :7831-7834

← 1 2 3 →