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-cytidine 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. A 2′,3′-dideoxy, 3′-amino-cytidine 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.
3. The monomer of claim 2 , wherein the alkyl is C 1 -C 4 alkyl and said cycloalkyl is C 5 -C 6 cycloalkyl.
4. The monomer of claim 2 , wherein the 3′-amino group protected with an acid-labile group.
5. The monomer of claim 4 , wherein the acid labile protecting group is a triarylmethyl group.
6. The monomer of claim 2 , wherein the 3′-amino group is protected with a fluorenylmethoxycarbonyl group or a derivative of a fluorenylmethoxycarbonyl group.
7. The monomer of claim 2 , wherein the nucleoside base is protected with a dimethylformamidinyl group or a dibenzylformamidinyl group.
8. The monomer of claim 2 , wherein the nucleoside base is protected with a dimethylformamidinyl group.
9. The monomer of claim 1 , wherein the alkyl is C 1 -C 4 alkyl and said cycloalkyl is C 5 -C 6 cycloalkyl.
10. The monomer of claim 1 , wherein the 3′-amino group protected with an acid-labile group.
11. The monomer of claim 10 , wherein the acid labile protecting group is a triarylmethyl group.
12. The monomer of claim 1 , wherein the 3′-amino group is protected with a fluorenylmethoxycarbonyl group or a derivative of a fluorenylmethoxycarbonyl group.
13. The monomer of claim 1 , wherein the nucleoside base is protected with a dimethylformamidinyl group or a dibenzylformamidinyl group.
14. The monomer of claim 1 , wherein the nucleoside base is protected with a dimethylformamidinyl group.