Total synthesis and biological evaluation of ustiloxin natural products and two analogs

被引：21

作者：

Li, Pixu

Evans, Cory D.

Forbeck, Erin M.

Park, Haengsoon

Bai, Ruoli

Hamel, Ernest

Joullie, M. M. ^{[1
]}

机构：

[1] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Ft Detrick, MD 21702 USA

[2] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 18期

关键词：

ustiloxins D and F; tubulin inhibitor; phomopsin; total synthesis; biological evalution; antimitotic agent;

D O I：

10.1016/j.bmcl.2006.06.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthetic investigations of ustiloxin natural products are described. The first total synthesis of ustiloxin F was completed in 15 steps via ethynyl aziridine ring-opening by a phenol derivative. The results of biological tests of synthetic ustiloxins D and F, and two analogs, O-Me-ustiloxin D and 6-Ile-ustiloxin, demonstrated that the free hydroxyl group ortho to the ether linkage is critical for activity and variations at the Val/Ala site produce changes in the biological activity suggesting the need for further perturbations at this site to more extensively study the tubulin binding. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：4804 / 4807

页数：4

共 23 条

[1]

BAI R, 1990, BIOCHEM PHARMACOL, V39, P194

[2]

BEULSHAUSEN T, 1992, LIEBIGS ANN CHEM, P523

[3] Total synthesis of ustiloxin D [J].

Cao, B ;

Park, H ;

Joullié, MM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (04) :520-521

[4]

CAO B, 2002, THESIS U PENNSYLVANI

[5] STRUCTURE ELUCIDATION AND ABSOLUTE-CONFIGURATION OF PHOMOPSIN-A, A HEXAPEPTIDE MYCOTOXIN PRODUCED BY PHOMOPSIS-LEPTOSTROMIFORMIS [J].

CULVENOR, CCJ ;

EDGAR, JA ;

MACKAY, MF ;

GORSTALLMAN, CP ;

MARASAS, WFO ;

STEYN, PS ;

VLEGGAAR, R ;

WESSELS, PL .

TETRAHEDRON, 1989, 45 (08) :2351-2372

[6]

CULVENOR CCJ, 1977, AUST J BIOL SCI, V30, P269, DOI 10.1071/BI9770269

[7] PATHOGENESIS OF MOUSE LUPINOSIS INDUCED BY A FUNGUS (CYTOSPORA SSP) GROWING ON DEAD LUPINS [J].

GARDINER, MR ;

PETTERSON, DS .

JOURNAL OF COMPARATIVE PATHOLOGY, 1972, 82 (01) :5-+

[8] Evaluation of antimitotic agents by quantitative comparisons of their effects on the polymerization of purified tubulin [J].

Hamel, E .

CELL BIOCHEMISTRY AND BIOPHYSICS, 2003, 38 (01) :1-21

[9] Interactions of antimitotic peptides and depsipeptides with tubulin [J].

Hamel, E .

BIOPOLYMERS, 2002, 66 (03) :142-160

[10]

Hamel E, 1996, MED RES REV, V16, P207, DOI 10.1002/(SICI)1098-1128(199603)16:2<207::AID-MED4>3.3.CO

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