Synthesis of d- ribo- and l- lyxo-phytosphingosine: Transformation into the corresponding lactosyl-ceramides

Abstract

2,4- O-Benzylidene- d-threose ( 2) reacted with tetradecylmagnesium bromide to give the d- arabino- and the l- xylo-octadecanetetrol derivatives 3a and 3x as a readily separable mixture. Each of these compounds was transformed, via regioselective mesylation, azide displacement, benzylidene cleavage, and azide reduction, into d- ribo- ( 1r) and l- lyxo-phytosphingosine ( 1l), respectively. 3,4- O-Isopropylidenation of the intermediate azido derivatives 7r and 7l afforded the 1- O-glycosyl acceptors 2-azido-3,4- O-isopropylidene- d- ribo-1,3,4-octadecanetriol ( 8r) and 2-azido-3,4- O-isopropylidene- l- lyxo-1,3,4-octadecanetriol ( 8l), respectively. With the trichloroacetimidate-activated lactosyl donor 9, the expected glycosides 2-azido-1- O-(2,3,6,2′,3′,4′,6′-hepta- O-acetyl-β-lactosyl)-3,4- O-isopropylidene- d- ribo- and - l- lyxo-1,3,4-octadecanetriol ( 10r and 10l) were obtained, which were conveniently transformed into the corresponding unprotected glycosphingolipids 14r and 14l