Synthesis of sphingomyelin difluoromethylene analogue

As a new sphingomyelinase inhibitor, a novel sphingomyelin CF2 analogue was designed and synthesized. One key step of this synthesis is the very mild hydrolysis of the oxazolidinone ring, a suitable intermediate for the introduction of a diethyl difluoromethylphosphonate group, by utilizing the characteristic electron withdrawing nature of the nosyl group at the oxazolidinone ring in an alcoholic solvent to produce the corresponding carbonate attaching at the secondary hydroxy group. The synthesized CF2 analogue inactivated toward B. cereus sphingomyelinase with nearly the same attitude as the nitrogen analogue that we previously reported. (c) 2006 Elsevier Ltd. All rights reserved.