Synthesis and biological evaluation of (-)-laulimalide analogues

被引：45

作者：

Wender, PA ^{[1
]}

Hegde, SG

Hubbard, RD

Zhang, L

Mooberry, SL

机构：

[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

[2] SW Fdn Biomed Res, Dept Physiol & Med, San Antonio, TX 78245 USA

来源：

ORGANIC LETTERS | 2003年 / 5卷 / 19期

关键词：

D O I：

10.1021/ol035339f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] The syntheses of five laulimalide analogues are described, incorporating modifications at the C-16-C-17-epoxide, the C-20-alcohol, as well as the C-1-C-3-enoate of the parent natural product. The resultant analogues are active in drug-sensitive HeLa and MDA-MB-435 cell lines. Significantly, like laulimalide, these analogues are poor substrates for the drug transport protein P-glycoprotein (Pgp) and are thus effective against Taxol-resistant cell lines.

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页码：3507 / 3509

页数：3

相关论文

共 22 条

[11] The molecular pharmacology of symplostatin 1: A new antimitotic dolastatin 10 analog [J].

Mooberry, SL ;

Leal, RM ;

Tinley, TL ;

Luesch, H ;

Moore, RE ;

Corbett, TH .

INTERNATIONAL JOURNAL OF CANCER, 2003, 104 (04) :512-521

[12]

MOOBERRY SL, 1977, CANCER RES, V37, P159

[13]

Mulzer J, 2001, ANGEW CHEM INT EDIT, V40, P3842, DOI 10.1002/1521-3773(20011015)40:20<3842::AID-ANIE3842>3.0.CO

[14]

2-R

[15] A de novo enantioselective total synthesis of (-)-laulimalide [J].

Nelson, SG ;

Cheung, WS ;

Kassick, AJ ;

Hilfiker, MA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (46) :13654-13655

[16] Total synthesis of the microtubule-stabilizing agent (-)-laulimalide [J].

Paterson, I ;

De Savi, C ;

Tudge, M .

ORGANIC LETTERS, 2001, 3 (20) :3149-3152

[17]

PATERSON I, 2001, ORG LETT, V42, P796

[18] The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity [J].

Pryor, DE ;

O'Brate, A ;

Bilcer, G ;

Díaz, JF ;

Wang, YF ;

Wang, Y ;

Kabaki, M ;

Jung, MK ;

Andreu, JM ;

Ghosh, AK ;

Giannakakou, P ;

Hamel, E .

BIOCHEMISTRY, 2002, 41 (29) :9109-9115

[19] FIJIANOLIDES, POLYKETIDE HETEROCYCLES FROM A MARINE SPONGE [J].

QUINOA, E ;

KAKOU, Y ;

CREWS, P .

JOURNAL OF ORGANIC CHEMISTRY, 1988, 53 (15) :3642-3644

[20] Cell line designation change: Multidrug-resistant cell line in the NCI anticancer screen [J].

Scudiero, DA ;

Monks, A ;

Sausville, EA .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (11) :862-862