Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy towards synthesis of isofagomine and related biologically important azasugars

Abstract

Synthesis of isofagomine has been achieved by implementation of aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a key step. The above rearrangement has also been utilized in the synthesis of biologically important polyhydroxylated piperidine frameworks such as isogalactofagomine, ent-isogalactofagomine and their analogues and some other azasugars as glycosidase inhibitors.

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

“…For the synthesis of IGF ( 1 ) 45 , 47 – 52 the primary alcohol of 11 was selectively protected as a pivaloyl ester with PivCl to give 12 in 83% yield ( Fig. 2B ).…”

C‐Branched Imino Sugars: Synthesis and Biological Relevance

“…Intramolecular S N 2 cyclization in the presence of t BuOK led to the piperidine 95 . A cis ‐dihydroxylation followed by a final deprotection gave 37 The same pathway also allowed the preparation of piperidines 41 and 42 (Figure ), starting from N ‐glycosyl amides 96 and 97 , respectively.…”

Synthetic Pathways to 3,4,5‐Trihydroxypiperidines from the Chiral Pool

“…Reddy and Vankar synthesised 3,4,5‐trihydroxypiperidine meso ‐2 from the 3,4‐di‐ O ‐benzyl‐ d ‐arabinal 161 with key step being the aza‐Claisen rearrangement of intermediate 163 with trichloroacetonitrile to give an anomeric mixture of 164a and 164b (Scheme ). This rearrangement provides a mild and synthetically efficient tool for the synthesis of nitrogen containing natural products in organic as well as in medicinal chemistry .…”