Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues:: The power of sharpless' asymmetric epoxidation

被引：120

作者：

Ahmed, A ^{[1
]}

Hoegenauer, EK ^{[1
]}

Enev, VAS ^{[1
]}

Hanbauer, M ^{[1
]}

Kaehlig, H ^{[1
]}

Öhler, E ^{[1
]}

Mulzer, J ^{[1
]}

机构：

[1] Univ Vienna, Inst Organ Chem, A-1090 Vienna, Austria

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2003年 / 68卷 / 08期

关键词：

D O I：

10.1021/jo026743f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Three different routes are described for the synthesis of deoxylaulimalide (3), which is the immediate precursor of the marine sponge metabolite laulimalide (1). These routes mainly differ with respect to their ring closing step. Thus, route 1 uses a Still-Gennari olefination, route 2 a Yamaguchi lactonization, and route 3 an intramolecular allylsilane-aldehyde addition for establishing the macrocyclic structure. The unprotected deoxy derivative 3 was subjected to Sharpless' asymmetric epoxidation (SAE). With (R,R)-tartrate the 16,17-epoxide laulimalide (1) is formed selectively, whereas (S,S)-tartrate generates the 21,22-epoxide 142. This demonstrates the high reagent control involved in the SAE process, which in this case is used to achieve high stereo- and regioselectivity. Laulimalide and some derivatives thereof have been tested with respect to antitumor activity and compared to standard compounds paclitaxel and epothilone B.

引用

页码：3026 / 3042

页数：17

共 182 条

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