A Concise Synthesis of Globotriaosylsphingosine

✍ Scribed by Henrik Gold; Rolf G. Boot; Johannes M. F. G. Aerts; Herman S. Overkleeft; Jeroen D. C. Codée; Gijs A. van der Marel

• Book ID: 102830055
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 551 KB
• Volume: 2011
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.201001690

✦ Synopsis

Abstract

Globotriaosylsphingosine (lysoCTH) is produced in the cell by deacylation of the globo‐sphingolipid globotriaosylceramide. The latter compound is the major storage material encountered in Fabry patients, an inherited lysosomal storage disorder characterized by partially impaired α‐galactosidase A (GLA) activity. Recent findings suggest that lysoCTH, next to its acylated precursor, is an important causative of Fabry disease symptoms. The glycolipid is thus a relevant synthetic target, and we here report on its efficient synthesis. Key to our strategy is the use of 4,6‐O‐di‐tert‐butylsilylene‐protected D‐galactose donors to yield D‐Gal‐α‐D‐Gal linkages with high stereoselectivity. In our optimized route we make use of acyl protecting groups to mask most of the hydroxy functions in the carbohydrate building blocks to facilitate straightforward global deprotection.