Synthesis of Novel Iminosugar Derivatives Based on a 2-Azabi­cyclo[4.1.0]heptane Skeleton

Abstract

Iminosugars are good starting points for the development of different kinds of drugs. Many are polyhydroxylated piperidines that behave as biomimetics of their corresponding pyranoses analogues. In the interaction with carbohydrate processing enzymes, selectivity is a crucial issue and the benefits of introducing a cyclopropane bridge in a piperidine structure is demonstrated. The synthesis of novel bicyclic piperidine-based iminosugars using a sulfur ylide cyclopropanation as the key synthetic step is described.

Conformationally constrained fused bicyclic iminosugars: synthetic challenges and opportunities

“…The only methodology reported to date for the formation of cyclopropane-based bicyclic iminosugars is the cyclopropanation of the appropriate alkene derivatives. [41][42][43] Using this methodology, fused iminosugar 51 was prepared in three steps from imino glucal 49 which was synthesized by treatment of 48 with oxalyl chloride (Scheme 9). 41 Cyclopropanation of 49 using diethylzinc and diiodomethane led to compound 50 in 64% yield after deprotection of the Fmoc group.…”

“…Recently, the synthesis of fused iminosugars based on a 2-azabicyclo[4.1.0]heptane skeleton using a sulfur ylid cyclopropanation as the key step has been reported in the literature. 43 Treatment of enaminone 59 with (2-ethoxy-2oxoethyl)dimethylsulfonium and DBU under microwave heating afforded, after reduction, the racemic cyclopropane 60 in high diastereoselectivity (Scheme 11). Dehydration of compound 60 by Grieco elimination furnished alkene 61 in 83% yield.…”

Synthesis and Evaluation of Novel Iminosugars Prepared from Natural Amino Acids

“…Our group engaged in the synthesis of novel piperidine iminosugars fused to a cyclopropane ring, resulting in structures with a locked conformation [ 10 , 11 ]. The cyclopropane renders a twist-like conformation to the piperidine ring that is found, as preferred for interactions with certain glycosidases [ 12 , 13 ].…”