Synthesis of glyceryl glycosides related to A-type prymnesin toxins

A suite of glycosylated glycerol derivatives representing various fragments of the glycosylated ichthyotoxins called prymnesins were chemically synthesised. Glycerol was used to represent a small fragment of the prymnesin backbone, and was glycosylated at the 2° position with the sugars currently reported to be present on prymnesin toxins. Neighbouring group participation was utilised to synthesise 1,2-trans-glycosides. SnCl₂-promoted glycosylation with furanosyl fluorides gave 1,2-cis-furanosides with moderate stereocontrol, whilst TMSOTf promoted glycosylation with a furanosyl imidate gave a 1,2-cis-furanoside with good stereocontrol. The chemical synthesis of two larger glyceryl diglycoside fragments of prymnesin-1, glycosylated with α-ʟ-arabinopyranose and α-ᴅ-ribofuranose, is also described. As the stereochemistry of the prymnesin backbones at this region is undefined, both the 2R- and 2S- glycerol isomers were synthesised. The separated diastereoisomers were distinguished by comparing NOESY NMR with computational models.