Stereoselective synthesis of 1-C-alkyl iminogalactitol derivatives, potential chaperones for galactosidase-linked LSDs: a real challenge

1-C-Alkyl iminogalactitol derivatives are highly desirable target compounds as potential pharmacological chaperones for the treatment of galactosidase-linked lysosomal storage disorders (LSDs). The synthesis of such compounds from d-galactose by a C-1 chain extension process by way of an open-chain 6-amino d-gulo nonulose intermediate was complicated by unexpected deoxygenation reactions leading to 3-deoxy iminogalactitol derivatives and epimers; an alternative, stereocontrolled synthesis from an l-tagatose derivative by C-6 chain-extension was therefore developed, which involved addition of organometallic reagents onto t-butanesulfinylimine intermediates in the key step.