A Gram-Scale Batch and Flow Total Synthesis of Perhydrohistrionicotoxin

被引：53

作者：

Brasholz, Malte ^{[1
]}

Macdonald, James M. ^{[1
]}

Saubern, Simon ^{[1
]}

Ryan, John H. ^{[1
]}

Holmes, Andrew B. ^{[1
,2
]}

机构：

[1] CSIRO Mol & Hlth Technol, Clayton, Vic 3168, Australia

[2] Univ Melbourne, Sch Chem, Bio Inst 21, Parkville, Vic 3010, Australia

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2010年 / 16卷 / 37期

基金：

澳大利亚研究理事会;

关键词：

alkaloids; cycloaddition; flow chemistry; olefination; total synthesis; DIPOLAR CYCLOADDITION ROUTES; ORGANIC-SYNTHESIS; 2-DIRECTIONAL SYNTHESIS; MULTISTEP SYNTHESIS; HISTRIONICOTOXIN FAMILY; FORMAL SYNTHESIS; (-)-HISTRIONICOTOXIN; MICROREACTOR; ALKALOIDS; CHEMISTRY;

D O I：

10.1002/chem.201001435

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The total synthesis of the spiropiperidine alkaloid (-)-perhydrohistrionicotoxin (perhydro-HTX) 2 has been accomplished on a gram scale by employing both conventional batch chemistry as well as microreactor techniques. (S)-(-)-6-Pentyltetrahydropyran-2-one 8 underwent nucleophilic ring opening to afford the alcohol 10, which was elaborated to the nitrone 13. Protection of the nitrone as the 1,3-adduct of styrene and side-chain extension to the unsaturated nitrile afforded a precursor 17, which underwent dipolar cycloreversion and 1,3-dipolar cycloaddition to give the core spirocyclic precursor 18 that was converted into perhydro-HTX 2. The principal steps to the spirocycle 18 have successfully been transferred into flow mode by using different types of microreactors and in a telescoped fashion, allowing for a more rapid access to the histrionicotoxins and their analogues by continuous processing.

引用

页码：11471 / 11480

页数：10

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