Phosphoramidite derivatives of texaphyrins

• US 5,633,354 A
• Filed: 03/13/1996
• Issued: 05/27/1997
• Est. Priority Date: 09/21/1994
• Status: Expired due to Fees

• Current Assignee: Pharmacyclics Incorporated (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Sessler, Jonathan L., Iverson, Brent L., Magda, Darren, Sansom, Petra I., Crofts, Shaun P.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US08/614,638
• Time in Patent Office: 440 Days
• Field of Search: 534/11, 534/13, 534/15, 534/16, 536/17.1, 536/17.3, 536/17.4, 540/145, 540/465, 540/472
• US Class Current: 534/15
• CPC Class Codes: A61K 47/546 Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

The invention is directed to a method of incorporating expanded porphyrins, and particularly of incorporating a sapphyrin or a texaphyrin, before, during, or after chemical synthesis of an oligomer to form an expanded porphyrin-oligonucleotide conjugate, and particularly a sapphyrin- or texaphyrin-oligonucleotide conjugate. This method includes reacting derivatized nucleotides and a sapphyrin or a texaphyrin in a desired order in an automated or manual DNA synthesizer having a solid support to form a sapphyrin- or a texaphyrin-oligonucleotide conjugate.

Claims

1. A phosphoramidite derivative of a texaphyrin metal complex.

2. A phosphoramidite derivative of a texaphyrin metal complex, said derivative having the following formula:

##STR5## wherein, M is a divalent metal cation or a trivalent metal cation;

R₁ -R₄, R₇ and R₈ are independently hydrogen, halide, hydroxyl, alkyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamide, carboxyamidealkyl, aminoalkyl, sulfonatoalkyl, amidealkyl, aryl, aralkyl, phosphoramidityl, alkylphosphoramidityl, or alkoxyphosphoramidityl, with the proviso that one of R₁ -R₄, R₇ and R₈ is phosphoramidityl, alkylphosphoramidityl, or alkoxyphosphoramidityl;

R₆ and R₉ are independently selected from the groups of R₁ -R₄, R₇ and R₈, with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl;

R₅ and R₁₀ -R₁₂ are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, or carboxyamidealkyl; and

Z is an integer less than or equal to 5.

3. A phosphoramidite derivative of a texaphyrin according to claim 2 wherein R₁ is alkyl or hydroxyalkyl;

R₂, R₃ and R₄ are alkyl;

R₅, R₆, and R₉ -R₁ are hydrogen; and

one of R₇ and R₈ is phosphoramidityl, alkylphosphoramidityl, or alkoxyphosphoramidityl.

4. A phosphoramidite derivative of a texaphyrin according to claim 2 wherein R₁ is CH₂ CH₃ or CH₂ CH₂ CH₂ OH;

R₂ and R₃ are CH₂ CH₃ ;

R₄ is CH₃ ;

R₅, R₆, and R₉ -R₁₂ are H;

R₇ is H, OCH₃ or O(CH₂ CH₂ O)₂ CH₂ CH₂ OCH₃ ; and

R₈ is alkoxyphosphoramidityl where the alkoxy has from one to ten carbon atoms.

5. A phosphoramidite derivative of a texaphyrin according to claim 4 wherein R₈ is alkoxyphosphoramidityl where the alkoxy has from three to six carbon atoms.

6. A phosphoramidite derivative of a texaphyrin according to claim 4 wherein R₈ is 3-{β

-cyanoethyl-N,N-bis(diisopropyl)phosphoramidityl}propoxy or 6-{β

-cyanoethyl-N,N-bis(diisopropyl)phosphoramidityl}hexanoxy.

7. A phosphoramidite derivative of a texaphyrin according to claim 2 wherein M is selected from the group consisting of Y(III), Mn(II), Mn(III), Fe(II), Fe(III), and the lanthanide metals.

8. A phosphoramidite derivative of a texaphyrin according to claim 2 wherein M is selected from the group consisting of Gd(III), Dy(III), Eu(III), La(III), Lu(III), Tb(III), and Y(III).

9. A phosphoramidite derivative of a texaphyrin according to claim 3 wherein M is selected from the group consisting of Y(III), Mn(II), Mn(III), Fe(II), Fe(III), and the lanthanide metals.

10. A phosphoramidite derivative of a texaphyrin according to claim 3 wherein M is selected from the group consisting of Gd(III), Dy(III), Eu(III), La(III), Lu(III), Tb(III), and Y(III).

11. A phosphoramidite derivative of a texaphyrin according to claim 4 wherein M is selected from the group consisting of Y(III), Mn(II), Mn(III), Fe(II), Fe(III), and the lanthanide metals.

12. A phosphoramidite derivative of a texaphyrin according to claim 4 wherein M is selected from the group consisting of Gd(III), Dy(III), Eu(III), La(III), Lu(III), Tb(III), and Y(III).

13. A phosphoramidite derivative of a texaphyrin metal complex, said derivative having the following formula:

##STR6## wherein, M is a divalent metal cation or a trivalent metal cation, and n is an integer from 1 to 10.

14. A phosphoramidite derivative of a texaphyrin according to claim 13 wherein n is an integer from 3 to 6, and M is selected from the group consisting of Y(III), Mn(II), Mn(III), Fe(II), Fe(III), and the lanthanide metals.

15. A phosphoramidite derivative of a texaphyrin according to claim 13 wherei. n is 3 or 6, and M is selected from the group consisting of Gd(III), Dy(III), Eu(III), La(III), Lu(III), Tb(III) and Y(III).

16. A phosphoramidite derivative of a texaphyrin metal complex, said derivative having the following formula:

##STR7## wherein, M is a divalent metal cation or a trivalent metal cation, Bz is a protecting group, and n is an integer from 1 to 10.

17. A phosphoramidite derivative of a texaphyrin according to claim 16 wherein n is an integer from 3 to 6, and M is selected from the group consisting of Y(III), Mn(II), Mn(III), Fe(II), Fe(III), and the lanthanide metals.

18. A phosphoramidite derivative of a texaphyrin according to claim 16 wherein n is 3 or 6, and M is selected from the group consisting of Gd(III), Dy(III), Eu(III), La(III), Lu(III), Tb(III) and Y(III).