Ar. Pagano et al., SYNTHESES OF [1,7-N-15(2)]- AND [1,7,NH2-N-15(3)]ADENOSINE AND 2'-DEOXYADENOSINE VIA AN N-1-ALKOXY-MEDIATED DIMROTH REARRANGEMENT, Journal of organic chemistry, 63(10), 1998, pp. 3213-3217
We have found that the N-1-methoxy derivatives of adenosine and 2'-deo
xyadenosine undergo a Dimroth rearrangement in which the intermediate
N,N-dimethylamino adducts are stable compounds. This mild and high-yie
ld rearrangement allows efficient conversion of [7,NH2-N-15(2)]2'-deox
yadenosine and [7,NH2-N-15(2)]adenosine into the triply labeled [1,7,N
H2-N-15(3)] derivatives. The [7,NH2-N-15(2)]nucleoside is first oxidiz
ed to the N-1-oxide with 3-chloroperoxybenzoic acid (MCPBA). Methylati
on of the N-1-oxide with methyl iodide or dimethyl sulfate is followed
by treatment with dimethylamine to afford the 6-amino-N-1-methoxy-2-(
N,N-dimethylamino) derivative. Dimroth rearrangement of these surprisi
ngly stable intermediates is accomplished by refluxing in the presence
of a dimethylammonium hydrohalide salt to give the [1,7-N-15(2)]-6-N-
methoxy nucleosides in high yield. Removal of the N-6-methoxy function
to afford both [1,7-N-15(2)]deoxyadenosine and [1,7-N-15(2)]adenosine
was accomplished readily with Raney nickel. No hydroxyl protection is
required for these transformations. Introduction of the third label a
t the N-6 was accomplished by conversion into the 6-(1,2,4-triazol-4-y
l)purine nucleosides, followed by nucleophilic displacement of the 6-t
riazole with [N-15]ammonia to afford the triply labeled title compound
s.