A Novel Approach to Both the Enantiomers of Potent Glycosidase Inhibitor Isofagomine via PET-Promoted Cyclization of 1-[Benzyl(trimethylsilyl-methyl)amino]-1,4,5-trideoxy-2,3-O-(1-methylethylidene)-threo-pent-4-ynitol

Abstract

The cyclization of PET-generated α-trimethylsilylmethylamine radical cation to a tethered acetylene moiety has been exploited to solve the problem of the generation of an aminomethyl group next to a stereocenter in the synthesis of 1-N-iminosugar type glycosidase inhibitors. Its success is demonstrated by the synthesis of (+)- as well as (-)-isofagomine, an extremely potent β-glucosidase inhibitor of the 1-N-iminosugar class.

photoinduced electron transfer (PET) - α-trimethylsilylmethylamine radical cation - glycosidase inhibitors - 1-N-iminosugars - isofagomine

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21

The amine PhCH₂NHCH₂TMS can be obtained commercially or can also be prepared easily by refluxing a (1:1) mixture of benzyl amine and chloromethyltrimethyl-silane in anhyd MeCN in the presence of anhyd K₂CO₃ for about 8 h.