Development of a practical and scalable route for the preparation of the deacetoxytubuvaline (dTuv) fragment of pretubulysin and analogs

被引：5

作者：

Brindisi, Margherita ^{[1
,2
]}

Maramai, Samuele ^{[1
,2
]}

Grillo, Alessandro ^{[1
,2
]}

Brogi, Simone ^{[1
,2
]}

Butini, Stefania ^{[1
,2
]}

Novellino, Ettore ^{[1
,3
]}

Campiani, Giuseppe ^{[1
,2
]}

Gemma, Sandra ^{[1
,2
]}

机构：

[1] Univ Siena, European Res Ctr Drug Discovery & Dev NatSynDrugs, Via Aldo Moro 2, I-53100 Siena, Italy

[2] Ist Toscano Tumori, Genoa, Italy

[3] Univ Naples Federico II, Dipartimento Farm, Via D Montesano 49, I-80131 Naples, Italy

来源：

TETRAHEDRON LETTERS | 2016年 / 57卷 / 08期

关键词：

Anticancer agents; Pretubulysin; Deacetoxytubuvaline; Scalable synthesis; BIOLOGICAL-PROPERTIES; TUBULIN; DERIVATIVES; ANTICANCER; INHIBITORS; POTENT; TARGET; IDENTIFICATION; MYXOBACTERIA; TUBULYSINS;

D O I：

10.1016/j.tetlet.2016.01.051

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We present herein a novel and convenient route for the scaling-up of the dTuv fragment of pretubulysin. The newly conceived chemical path involves a practical and efficient one-step procedure for the preparation of a key thiazole intermediate, followed by high-yielding Wittig olefinationfreduction steps. The optimized route, starting from the inexpensive and non-toxic L-cysteine, encompasses five synthetic steps and only two chromatographic purifications, thus displaying a dramatically increased overall yield. The versatility of the proposed approach also provides new hints for the exploration of pretubulysin derivatives bearing diverse heterocyclic portions. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：920 / 923

页数：4

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