Synthesis and Biological Evaluation of C(13)/C(13′)-Bis(desmethyl)disorazole Z

被引：5

作者：

Bold, Christian Paul ^{[1
]}

Lucena-Agell, Daniel ^{[2
]}

Angela Oliva, Maria ^{[2
]}

Fernando Diaz, Jose ^{[2
]}

Altmann, Karl-Heinz ^{[1
]}

机构：

[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, Vladimir Prelog Weg 4, CH-8093 Zurich, Switzerland

[2] CSIC, Ctr Invest Biol Margarita Salas, Ramiro Maeztu 9, Madrid 28040, Spain

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2023年 / 62卷 / 05期

关键词：

Cross-Coupling; Cyclodimerization; Disorazoles; Microtubule-Interacting Agents; Total Synthesis; DOUBLE ALDOL REACTION; STEREOSELECTIVE-SYNTHESIS; CARBOXYLIC ESTERS; MIXED ANHYDRIDE; DISORAZOLE C-1; BINDING; ACIDS; SITE; ESTERIFICATION; METABOLITES;

D O I：

10.1002/anie.202212190

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We describe the total synthesis of the macrodiolide C(13)/C(13 ')-bis(desmethyl)disorazole Z through double inter-/intramolecular Stille cross-coupling of a monomeric vinyl stannane/vinyl iodide precursor to form the macrocycle. The key step in the synthesis of this precursor was a stereoselective aldol reaction of a formal Evans acetate aldol product with crotonaldehyde. As demonstrated by X-ray crystallography, the binding mode of C(13)/C(13 ')-bis(desmethyl)disorazole Z to tubulin is virtually identical with that of the natural product disorazole Z. Likewise, C(13)/C(13 ')-bis(desmethyl)disorazole Z inhibits tubulin assembly with at least the same potency as disorazole Z and it appears to be a more potent cell growth inhibitor.

引用

页数：8

共 71 条

[1] Boron-mediated double aldol reaction of carboxylic esters [J].

Abiko, A ;

Liu, JF ;

Buske, DC ;

Moriyama, S ;

Masamune, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (30) :7168-7169

[2] The first doubly borylated enolate as an intermediate of the double aldol reaction [J].

Abiko, A ;

Inoue, T ;

Furuno, H ;

Schwalbe, H ;

Fieres, C ;

Masamune, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (19) :4605-4606

[3]

Aicher B., 2011, MOL CANCER THER, V10, pC214, DOI DOI 10.1158/1535-7163.TARG-11-C214

[4] FDA Approval: Ado-Trastuzumab Emtansine for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer [J].

Amiri-Kordestani, Laleh ;

Blumenthal, Gideon M. ;

Xu, Qiang Casey ;

Zhang, Lijun ;

Tang, Shenghui W. ;

Ha, Linan ;

Weinberg, Wendy C. ;

Chi, Bo ;

Candau-Chacon, Reyes ;

Hughes, Patricia ;

Russell, Anne M. ;

Miksinski, Sarah Pope ;

Chen, Xiao Hong ;

McGuinn, W. David ;

Palmby, Todd ;

Schrieber, Sarah J. ;

Liu, Qi ;

Wang, Jian ;

Song, Pengfei ;

Mehrotra, Nitin ;

Skarupa, Lisa ;

Clouse, Kathleen ;

Al-Hakim, Ali ;

Sridhara, Rajeshwari ;

Ibrahim, Amna ;

Justice, Robert ;

Pazdur, Richard ;

Cortazar, Patricia .

CLINICAL CANCER RESEARCH, 2014, 20 (17) :4436-4441

[5] OXIDATION OF ALPHA,BETA-UNSATURATED ALDEHYDES [J].

BAL, BS ;

CHILDERS, WE ;

PINNICK, HW .

TETRAHEDRON, 1981, 37 (11) :2091-2096

[6]

Bold C. P.., UNPUB

[7] Microtubule interactions with chemically diverse stabilizing agents:: Thermodynamics of binding to the paclitaxel site predicts cytotoxicity [J].

Buey, RM ;

Barasoain, I ;

Jackson, E ;

Meyer, A ;

Giannakakou, P ;

Paterson, I ;

Mooberry, S ;

Andreu, JM ;

Díaz, JF .

CHEMISTRY & BIOLOGY, 2005, 12 (12) :1269-1279

[8] Palladium mediated spiroketal synthesis: application to pheromone synthesis [J].

Conway, JC ;

Quayle, P ;

Regan, AC ;

Urch, CJ .

TETRAHEDRON, 2005, 61 (50) :11910-11923

[9] Oxidative addition of N-halosuccinimides to palladium(0):: the discovery of neutral palladium(II) imidate complexes, which enhance Stille coupling of allylic and benzylic halides [J].

Crawforth, CM ;

Burling, S ;

Fairlamb, IJS ;

Kapdi, AR ;

Taylor, RJK ;

Whitwood, AC .

TETRAHEDRON, 2005, 61 (41) :9736-9751

[10]

De Lera A., 2003, United States Patent Application, Patent No. 6534545

← 1 2 3 4 5 6 7 8 →