Total Synthesis and Configurational Assignment of the Marine Natural Product Haliclamide

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• 作者：Bernhard Pfeiffer ; Sandra Speck-Gisler ; Luzi Barandun ; Ursula Senft ; Claire de Groot ; Ir猫ne Lehmann ; Walter Ganci ; J眉rg Gertsch ; Karl-Heinz Altmann
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：March 15, 2013
• 年：2013
• 卷：78
• 期：6
• 页码：2553-2563
• 全文大小：398K
• 年卷期：v.78,no.6(March 15, 2013)
• ISSN：1520-6904

文摘

The marine natural product haliclamide has been synthesized based on macrocyclization by ring-closing olefin metathesis. Using either enantiomer of two of the four building blocks that were employed to assemble the diene precursor for the metathesis reaction, three non-natural isomers of haliclamide were also prepared. On the basis of the comparison of the ¹H and ¹³C NMR spectra of the individual stereoisomers with literature data for the natural product, the configuration of the previously unassigned stereocenters at C9 and C20 of haliclamide could be determined to be S for both carbons. The absolute configuration of haliclamide thus is 2S, 9S, 14R, 20S. The antiproliferative activity of synthetic haliclamide against several human cancer cell lines was found to be in the high 渭M range. The compound showed no antifungal or antibiotic activity.