A convenient synthesis of 2'-deoxy-2-fluoroadenosine; a potential prodrug for suicide gene therapy.
A convenient synthesis of 2'-deoxy-2-fluoro-adenosine (1) is described. Deaminative fluorination of 2-aminoadenosine (2) followed by silylation of the 3', 5'-hydroxyl groups gave the corresponding 2-fluoroadenosine derivative 4 in good yield. Thiocarbonylation of 4 to thiocarbonylimidazolyl derivative 5a followed by treatment with an excess of tris(trimethylsilyl)silane (TTMSS) and tert-butyl peroxide in toluene at 80 degrees C was found to affect an efficient deoxygenation to the corresponding 2'-deoxy derivative 6. Desilylation of 6 by Et4NF in CH3CN afforded 1 in high yield.
Hassan
A E
AE
Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255-5305, USA.
Shortnacy-Fowler
A T
AT
Montgomery
J A
JA
Secrist
J A
JA
D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry; D015316:Genetic Therapy; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry
C412233:2'-deoxy-2-fluoroadenosine; D003839:Deoxyadenosines; D011355:Prodrugs; C033854:2-aminoadenosine; D000241:Adenosine