Hydroxymethyl-Branched Polyhydroxylated Indolizidines: Novel Selective 伪-Glucosidase Inhibitors

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• 作者：Julien Boisson ; Am茅lia Thomasset ; Emilie Racine ; Pascale Cividino ; Thomas Banchelin Sainte-Luce ; Jean-Fran莽ois Poisson ; Jean-Bernard Behr ; Sandrine Py
• 刊名：Organic Letters
• 出版年：2015
• 出版时间：August 7, 2015
• 年：2015
• 卷：17
• 期：15
• 页码：3662-3665
• 全文大小：400K
• ISSN：1523-7052

文摘

伪,伪-Disubstituted piperidines and conformationally constrained polyhydroxylated indolizidines bearing a hydroxymethyl substituent in position 8a were synthesized from a readily available l-sorbose-derived ketonitrone. Diastereoselective vinylation under two sets of complementary conditions allowed access to both configurations of the newly formed quaternary stereocenter. Subsequent N-allylation and ring-closing metathesis afforded 8a-branched indolizidines in high yield. The newly prepared iminosugars demonstrated highly potent inhibition of 伪-glucosidases. Most interestingly, compound 9b exhibits very high selectivity toward this class of enzymes, with an unusual mode of binding.