کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1362461 | 981488 | 2006 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 4,5-Diaryl-1H-pyrrole-2-carboxylates as combretastatin A-4/lamellarin T hybrids: Synthesis and evaluation as anti-mitotic and cytotoxic agents 4,5-Diaryl-1H-pyrrole-2-carboxylates as combretastatin A-4/lamellarin T hybrids: Synthesis and evaluation as anti-mitotic and cytotoxic agents](/preview/png/1362461.png)
The 4,5-diarylated-1H-pyrrole-2-carboxylates 3–8 have each been prepared as hybrids of the potent anti-mitotic agent combretastatin A-4 (1) and the similarly active marine alkaloid lamellarin T (2). The key steps involved selective lithium-for-halogen exchange at C5 within the N-PMB protected 4,5-dibromopyrrole 22 and Negishi cross-coupling of the derived zincated species with the relevant aryl iodide. The ensuing 5-aryl-4-bromopyrrole then engaged in Suzuki–Miyaura cross-coupling with the appropriate arylboronic acid to give the 4,5-diarylated pyrroles 4, 6 and 8. TFA-promoted removal of the N-PMB group within these last compounds then gave the N-unsubstituted congeners 3, 5 and 7. Compounds 3–8 have all been evaluated for their anti-mitotic and cytotoxic properties and two of them, 3 and 5, display useful activities although they are less potent than combretastatin A-4.
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Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 13, 1 July 2006, Pages 4627–4638