Synthesis of protected 3′-amino nucleoside monomers

Patent metadata

Field	Value
Publication number	US-10035815-B2
Application number	US-201615155781-A
Country	US
Kind code	B2
Filing date	May 16, 2016
Priority date	Jul 2, 2004
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

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.

First claim

It is claimed:

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.

Assignees

• Geron Corp

Inventors

• Gryaznov Sergei M
• Pongracz Krisztina
• Zielinska Daria

Classifications

• C07H19/12

  Triazine radicals · CPC title

• C07H19/16 Primary

  Purine radicals · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title

• C07H19/10

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title