Synthesis of protected 3′-amino nucleoside monomers
Orthogonally protected 3′-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3′-amino group in the presence of the unprotected nucleoside base.
1. A 2,3′-dideoxy, 3″-amino adenosine monomer or a 2′, 3′-dideoxy, 3′-amino guanosine monomer wherein the 2′-group of the monomer is hydrogen, and the monomer has a 3′-amino group protected with an acid-labile group or a fluorenylmethoxycarbonyl group or a derivative of a fluorenylmethoxycarbonyl group; a nucleoside base which is protected with a dialkyl-, di(cycloalkyl)- or di(aralkyl)-formamidinyl group; and an unprotected 5′-hydroxyl group.
2. The monomer of claim 1 , wherein said alkyl is C 1 -C 4 alkyl and said cycloalkyl is C 5 -C 6 cycloalkyl.
3. The monomer of claim 1 , wherein said acid labile protecting group is a triarylmethyl group.
4. The monomer of claim 1 , wherein said nucleoside base is protected with a dimethylformamidinyl group or a dibenzylformamidinyl group.
5. The monomer of claim 1 , wherein said nucleoside base is protected with a dimethylformamidinyl group.
6. The monomer of claim 1 , wherein the 3′-amino group is protected with a fluorenylmethoxycarbonyl group or a derivative of a fluorenylmethoxycarbonyl group.
7. A 2′,3′-dideoxy adenosine monomer or a 2′,3′-dideoxy, 3′-amino guanosine monomer wherein the 2′-group of the monomer is hydrogen and the monomer has a 3′-amino group protected with an acid-labile group or a fluorenylmethoxycarbonyl group or a derivative of a fluorenylmethoxycarbonyl group; a nucleoside base which is protected with a dialkyl-, di(cycloalkyl)- or di(aralkyl)-formamidinyl group; and a 5′-O-(2-cyanoethyl-N,N-diisopropylamino)phosphoramidite group.