title: Synthesis of sphingomyelin carbon analogues as sphingomyelinase inhibitors.
abstract: The highly efficient and stereocontrolled syntheses of sphingomyelin carbon analogues 1 and 2 were achieved by effectively utilizing Hofmann rearrangement of enantiomerically pure beta-hydroxyamide 7, which was prepared by an asymmetric hydrogenation of alpha-acyl-gamma-butyrolactone 9 and ring opening with NH(3). Intermediary isocyanate 6 was selectively trapped with the vicinal hydroxy group in an intramolecular fashion to produce an oxazolidinone derivative, 5. In the synthesis of a quite polar compound such as 1, a convenient one-pot procedure of the introduction of a benzyloxycarbonyl group into the hydroxy group resulting from the oxazolidinone ring opening is another key point, because, in addition to the efficiency, this protecting group was easily removable by a simple procedure and workup at the final step. Both synthesized compounds 1 and 2 showed moderate inhibitory activity toward sphingomyelinase from B. cereus.
authors.affiliation: School of Science, Kwansei Gakuin University, Gakuen, Sanda, Hyogo 669-1337, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hakogi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Monden
authors.forename: Misako
authors.initials: M
authors.lastname: Taichi
authors.forename: Seiji
authors.initials: S
authors.lastname: Iwama
authors.forename: Shinobu
authors.initials: S
authors.lastname: Fujii
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Katsumura
mesh_terms: D017209:Apoptosis; D001409:Bacillus cereus / Q000201:enzymology; D002625:Chemistry, Organic / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013109:Sphingomyelins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase