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

被引：42
作者：
Boisson, Julien [1 ,2 ]
Thomasset, Amelia [1 ,2 ]
Racine, Emilie [1 ,2 ]
Cividino, Pascale [1 ,2 ]
Sainte-Luce, Thomas Banchelin [1 ,2 ]
Poisson, Jean-Francois [1 ,2 ]
Behr, Jean-Bernard [3 ]
Py, Sandrine [1 ,2 ]
机构：
[1] Univ Grenoble Alpes, DCM, F-38000 Grenoble, France
[2] CNRS, DCM, F-38000 Grenoble, France
[3] Univ Reims, Inst Chim Mol Reims, CNRS UMR 7312, UFR Sci Exactes & Nat, F-51687 Reims 2, France
来源：
ORGANIC LETTERS | 2015年 / 17卷 / 15期
关键词：
NUCLEOPHILIC ADDITIONS; GLYCOSIDASE INHIBITORS; CYCLIC NITRONES; CHIRAL NITRONE; 1ST SYNTHESIS; PYRROLIDINE; IMINOSUGARS; ANALOGS; (+)-LENTIGINOSINE; CASTANOSPERMINE;
D O I：
10.1021/acs.orglett.5b01505
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
alpha alpha-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 alpha-glucosidases. Most interestingly, compound 9b exhibits very high selectivity toward this class of enzymes, with an unusual mode of binding.
引用
收藏
页码：3662 / 3665
页数：4
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