Reacción #696720

Ecuación de reacción

13

3'-O-t-Butyldiphenylsilyl-N6 -benzoyl-2'-O-methyladenosine

p-nitrobenzenesulfonyl chloride

LiN3

→

5'-azido-5'-deoxy

5'-Azido-5'-deoxy-3'-O-t-butyldiphenylsilyl-N6 -benzoyl-2'-O-methyladenosine

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroyielded unexpectedly
2. 2
   workup.ADDITIONa 2:1 mixture of 5'-O-p-nitrobenzenesulfonyl and 5'-chloro-5'-deoxy substituted derivatives 14 and 15

Procedimiento

The low selectivity in the tosylation of guanosine derivative 6 prompted us to to use 3'-hydroxyl protection in the preparation of adenosine analog. Thus, 5'-O-DMT derivative 12 was converted to 3'-O-TBDPSi derivative which was 5'-deprotected to yield 13 with TFA in CH2Cl2. The reaction of 13 with a more reactive sulfonylating agent, p-nitrobenzenesulfonyl chloride, yielded unexpectedly a 2:1 mixture of 5'-O-p-nitrobenzenesulfonyl and 5'-chloro-5'-deoxy substituted derivatives 14 and 15. The mixture was treated with LiN3 at 80° C. overnight to afford 5'-azido-5'-deoxy derivative 16 in good yield. Catalytic hydrogenation of 16 proceeded smoothly to afford 5'-amino derivative 17 which was, without purification converted to 5'-N-MMTr protected derivative 18. Cleavage of the 3'-O-TBDPSi group was achieved using tetrabutylammonium fluoride and the resulting 19 was phosphitylated under standard conditions to give the 3'-O-phosphoramidite 20 in 74% yield (FIG. 8C).

Fuente