Model Studies toward Scyphostatin: Synthesis of (S)-4-Benzyl-3-(p-toluenesulfonyl)-2-oxazolidinone and Its Effective Transformation to (S)-N-(1-Benzyl-2-hydroxyethyl)hexadecanamide

S)-4-Benzyl-3-(p-toluenesulfonyl)-2-oxazolidinone (6) was synthesized as a simplified model substrate for the cyclohexenone subunit (2) of scyphostatin (1) starting from L-phenylalanine (3).Transformation of 6 to (S)-N-(1-benzyl-2-hydroxyethyl)hexadecanamide (10) was efficiently achieved to develop a reliable protocol for the construction of the fatty acid-substituted aminopropanol side chain moiety present in 1; the method involves hydrolysis of the cyclic carbamate moiety, N-palmitoylation of the liberated N-Ts-amido function, and removal of the N-Ts protecting group as the crucial steps.Scyphostatin (1, Figure 1), a potent inhibitor of neutral sphingomyelinase (IC50=1.03][4] Structurally, this natural product possesses a novel, highly oxygenated cyclohexane ring connected with an unsaturated fatty acid-substituted aminopropanol side chain. 2,5,6Its promising biological profiles as well as unique