Synthesis and conformational and configurational studies of diastereoisomeric O-protected 4-(aryisulfonimidoyl)butane-1,2,3-triols

[摘要] Chiral sulfoximines have applications as transition-state mimicking enzyme inhibitors, as peptide isosteres and as chiral auxiliaries in synthesis. To access the required O-protected 4-(arylsulfonimidoyl)butane-1,2,3-triols, 4S,5S-di(hydroxymethyl)-2,2-dimethyl-1,3dioxolane (prepared from diethyl R,R-tartrate) was converted into its monobenzyl ether. Mitsunobu-like coupling with thiophenols gave 4S,5R-4-(benzyloxymethyl)-2,2-dimethyl-5-(arylthiomethyl)-1,3-dioxolanes. Sulfoxidation and S-imination (trifluoroacetamide, iodosobenzene iacetate, rhodium acetate) proceeded without stereoselectivity, giving inseparable diastereomeric mixtures of 4S,5R,S(+/-)-4-(benzyloxymethyl)-2,2-dimethyl-5-(N-(trifluoroacetyl)arylsulfonimidoylmethyl)-1,3-dioxolanes. Removal of the trifluoroacetyl protection allowed chromatographic separation of the diastereomeric 4S,5R,S(+/-)-4-(benzyloxymethyl)-2,2-dimethyl-5-(arylsulfonimidoylmethyl)1,3-dioxolanes. The configurations at sulfur were determined by X-ray crystallography and some analysis of the solution and solid-state conformations was carried out. The resulting O-protected 4-(arylsulfonimidoyl)butane-1, 2,3 -triols are of use in developing enzyme inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

[发布日期] 2007-12-17