Synthesis of 1-(2-Deoxy-2-C-fluoromethyl-β-D-arabinofuranosyl)cytosine as a potential antineoplastic agent

Recent advances in the synthesis of fluorinated nucleosides

“…In 1994, 2 0 -deoxy-2 0 -C-fluoromethylcytidine 164 (SFDC) was synthesized as a potential antineoplastic agent by Yoshimura and co-workers (Scheme 28). 32 The synthesis of the key intermediate, the fluoromethyl derivative 162, was carried out by the reaction between the 2 0 -ketouridine 161 and dimethylsulfoxonium iodide followed by cleavage of the oxirane ring with KF$HF. After the protecting groups were changed, the tertiary hydroxyl group was removed by radical deoxygenation using the methyl oxalyl-Bu 3 SnH system to give the 2 0 b-fluoromethyl derivative 163, which was further converted into the target nucleoside 164 via base-moiety transformation and deprotection.…”

Regio- and stereoselective synthesis of vicinal fluorohydrins

“…Many more applications of such regio-and stereoselective ring openings have been reported in the field of structural analogues of natural products including fluorinated sugars, [133] nucleosides, [134,135] and shikimic acid derivatives [136][137][138] to form fluorohydrins bearing fluorine atoms in different positions. Also optically active cyclitol derivatives were prepared by this type of epoxide ring opening.…”

Synthesis of 5-O-benzyl-2-C-β-fluoromethyl-1,2,3-tri-O-acetyl- D-ribofuranose

“…In the first example, ring-opening of epoxide (3) under harsh conditions gave 2´-C-α-fluoromethyl derivative (4), which was converted to 2´-C-β-fluoromethyl-2-deoxycytidine in six steps. 7 The fluorine was introduced similarly in the second example, and three further steps were required to afford 2´-C-β-fluoromethyluridine (5). 8 Two patents 4c,9 describe remarkably mild fluoride displacement of tosylate (6) and triflate (7) to give compounds (8) and (9), respectively.…”