A High Yield Synthesis of Phosphatidyl Ethanolamines Using Phosphoramidite Intermediates

Abstract

Alkyl 2-aminoethyl hydrogen phosphates (phosphatidyl ethanolamines) were prepared via phosphoramidite chemistry. tert-Butoxy-carbonyl N-protection of 2-aminoethanol, followed by cyclisation with phosphorus(III) chloride gave the phosphoramidite 3-tert-butoxycarbonyl-2-chloro-1,3, 2-oxazaphospholidine (3). This reacted with long chain alcohols (C6 to C18) to give 2-alkyloxy-3-tert-butoxycarbonyl-1,3,2-oxazaphospholidines 4a-d which were oxidised to 2-alkyloxy-3-tert-butoxycarbonyl-2-oxo-1,3, 2-oxazaphospholidines 5a-d with dinitrogen tetroxide. Simultaneous heterocycle cleavage and N-deprotection were achieved with refluxing aqueous tetrahydrofuran, to give the target 2-aminoethyl phosphates 6a-d. The reaction conditions are mild, and the yields are almost quantitative in terms of the long chain alcohol. The products and intermediates are fully characterised by a range of spectroscopic and analytical methods.