Synthesis of 1-β-D-arabinofuranosyl-cytosine 5'-phosphate-L-1,2-diacylglycerols

Article abstract of DOI:10.1016/S0009-3084(97)00056-X

5'-O-MMTr-cytosine arabinoside was prepared on a large scale from 5'-O-MMTr-cytidine with diphenyl carbonate via 5'-protected cytidine-2',3'-carbonate-ara-cytidine-2',2-anhydro derivative at a 67% yield. 1,2-Dipalmitoyl-sn-glycerol,1,2-distearoyl-sn-glycerol and 1,2-dioleoyl-sn-glycerol were phosphorylated first with 2-chlorphenyl-phosphorobis-triazolide quantitatively. This method was used in order to avoid acyl migration, then the glycerophosphate intermediates were condensed with 2',3',N⁴-trileulinyl-1-β-D-arabinofuranosylcytosine in the presence of 2-mesytilensulphonyl chloride (MSCl) and 1-methylimidazole (MeIm) - which was used in the coupling of nucleotides - in an 85-88% yield compared with the low yielding diester method of Ryu et al. Deblocking was carried out in two steps with tetrabutylammonium fluoride (TBAF) and hydrazine hydrate, producing target compounds (9a, 9b, 9c) at a 50% yield.