Stereoselective Synthesis of C-2 Alkylated Trihydroxypiperidines: Novel Pharmacological Chaperones for Gaucher Disease.

ABSTRACT: Pharmacological chaperones (PCs) are small molecules that bind and stabilize enzymes. They can rescue the enzymatic activity of misfolded or deficient enzymes when they are used at subinhibitory concentration, thus with minimal side effects. Pharmacological Chaperone Therapy (PCT) is an emerging treatment for many lysosomal storage disorders (LSDs) including Gaucher disease, the most common, which is characterized by a deficiency in the GCase enzyme. We report herein a straightforward synthetic strategy to afford C-2 substituted trihydroxypiperidines with different alkyl chains starting from low cost d-mannose. Stereoselective Grignard reagent addition onto a key nitrone intermediate in the presence or absence of a suitable Lewis acid afforded both epimers of the target compounds, after a

SUBMITTER: Clemente F 

PROVIDER: S-EPMC6467014 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature