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 synthetic preparation of a N3′→P5′ phosphoramidate or thiophosphoramidate oligonucleotide, comprising an oligonucleotide comprising a 3′-amino-3′-deoxy nucleoside monomer having a nucleoside base which is protected with a dialkyl-, di(cycloalkyl)- or di(aralkyl)-formamidinyl group,
wherein the 3′-amino nucleoside monomer is the 3′-terminal monomer.
2. The synthetic preparation of claim 1 , wherein the 3′-amino nucleoside monomer is a guanosine or an adenosine monomer.
3. The synthetic preparation of claim 1 , wherein the 3′-amino nucleoside monomer is a cytidine monomer.
4. The synthetic preparation of claim 1 , wherein the oligonucleotide comprises a deprotected 3′-amino for addition of a further monomer to the growing oligonucleotide chain.
5. The synthetic preparation of claim 1 , wherein the oligonucleotide is composed of 3′-amino-3′-deoxy nucleoside monomers independently selected from guanosine, adenosine, cytidine and thymidine, wherein all of the guanosine, adenosine and cytidine monomers have a nucleoside base which is protected with a dialkyl-, di(cycloalkyl)- or di(aralkyl)-formamidinyl group and all of the thymidine monomers have a unprotected nucleoside base.
6. A synthetic preparation of a N3′→P5′ phosphoramidate or thiophosphoramidate oligonucleotide, comprising an oligonucleotide comprising a 3′-amino-3′-deoxy nucleoside monomer having a nucleoside base which is protected with a dialkyl-, di(cycloalkyl)- or di(aralkyl)-formamidinyl group,
wherein the oligonucleotide comprises a deprotected 3′-amino for addition of a further monomer to the growing oligonucleotide chain.
7. The synthetic preparation of claim 6 , wherein the 3′-amino nucleoside monomer is a guanosine or an adenosine monomer.
8. The synthetic preparation of claim 6 , wherein the 3′-amino nucleoside monomer is a cytidine monomer.
9. The synthetic preparation of claim 6 , wherein the 3′-amino nucleoside monomer is the 3′-terminal monomer.
10. The synthetic preparation of claim 6 , wherein the oligonucleotide is composed of 3′-amino-3′-deoxy nucleoside monomers independently selected from guanosine, adenosine, cytidine and thymidine, wherein all of the guanosine, adenosine and cytidine monomers have a nucleoside base which is protected with a dialkyl-, di(cycloalkyl)- or di(aralkyl)-formamidinyl group and all of the thymidine monomers have a unprotected nucleoside base.