A stereocontrolled total synthesis of C-nucleosides

Article abstract of DOI:10.1246/bcsj.57.2515

A stereocontrolled, general synthesis of chiral C-nucleosides has been achieved through a common lactonic C- beta -glycoside intermediate which is readily obtainable from non-carbohydrate materials. The optically pure lactone having the natural D configuration is obtained through optical resolution of the seco acid by the Pirkle's method followed by relactonization. alpha -Aminomethylenation of the lactone with t-C//4H//9OCH left bracket N(CH//3 )//2 right bracket //2 yields 2-(2,3-0-isopropylidene- beta -D-ribofuranosyl)-2-(dimethylaminomethylene)acetic acid lactone, which undergoes base-assisted condensation with urea followed by deprotection to furnish naturally occurring pseudouridine. Analogously, construction of heterocycles using thiourea and guanidine converts the aminomethylene lactone to unnatural pyrimidine C-nucelosides, 2-thiopseudouridine and pseudoisocytidine, respectively.