Miglustat

Description

This orally active glucosylceramide glucosyltransferase inhibitor, was launched for the treatment of type I Gaucher’s disease. Miglustat (XVI) has been developed and launched by Oxford GlycoSciences (OGS; now Celltech) and Actelion.

Uses

Treatment of glycolipid storage diseases.

brand name

Zavesca(Actelion).

Synthesis

Miglustat was originally discovered at Searle (now Pfizer) and an enzymatic oxidation was employed in the synthesis. D-Glucose (125) was subjected to reductive amination with n-butylamine in ethanol under 4 atm of hydrogen in the presence of Pd/C catalyst at 60 oC to give N-butylglucamine HCl salt (126) in 90% yield. Nbutylglucamine (126) then was submitted to a selective microorganism oxidation by Gluconobacter Oxidans (DSM 2003) cell paste in water to give 6-(butylamino)-6-deoxy-a- L-sorbofuranose HCl salt (127) in 80 % yield. Finally, compound 127 was cyclized and reduced in situ with hydrogen over Pd/C at 4000 atm in ethanol/water to give miglustat (XVI) in 45% overall yield from D-glucose (125).

Raw materials

Preparation Products