Extended rhodamine compounds useful as fluorescent labels

• US 6,248,884 B1
• Filed: 06/03/1999
• Issued: 06/19/2001
• Est. Priority Date: 06/03/1999
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Perkinelmer Incorporated
• Inventors: Lam, Joe Y. L., Menchen, Steven M., Benson, Scott C.
• Primary Examiner(s): Rotman, Alan L.
• Assistant Examiner(s): COVINGTON, RAYMOND K
• Application Number:
  US09/325,243
• Time in Patent Office: 747 Days
• Field of Search: 549/384, 549/382, 546/101, 546/104, 546/108, 546/111, 546/75, 546/73, 546/71, 546/28, 546/36, 546/79, 546/41, 544/180, 544/336, 544/359, 544/63, 548/250, 548/206, 548/311.4, 548/311.7, 548/240, 548/131
• US Class Current: 544/59
• CPC Class Codes: C07D 209/60 Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
• CPC Class Codes: C07D 221/08 Aza-anthracenes
• CPC Class Codes: C07D 221/10 Aza-phenanthrenes
• CPC Class Codes: C07D 471/06 Peri-condensed systems
• CPC Class Codes: C07D 487/06 Peri-condensed systems
• CPC Class Codes: C07D 491/14 Ortho-condensed systems
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• 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
• CPC Class Codes: C09B 11/24 Phthaleins containing amino groups ; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
• CPC Class Codes: Y10S 435/975 Kit
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

Extended rhodamine compounds exhibiting favorable fluorescence characteristics having the structure

are disclosed. In addition, novel intermediates for synthesis of these dyes are disclosed, such intermediates having the structure

In addition, methods of making and using the dyes as fluorescent labels are disclosed.

Claims

1. An extended rhodamine compound having the structure

wherein

R₁ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₁ taken together with R₂, Y₁, or Y₂ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₂ taken alone is selected from the group consisting of —

H alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O))₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₂ taken together with R₁ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₃ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₃ taken together with R₄ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₄ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₄ taken together with R₃, Y₃, or Y₄ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₅ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₅ taken together with R₆, Y₃, or Y₄ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₆ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂R, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₆ taken together with R₅, R₇, Y₃, or Y₄ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₇ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₇ taken together with R⁶ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₈ is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁;

R₉ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R,—

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₉ taken together with R₁₀ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₁₀ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR,—

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR, —

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₁₀ taken together with R₉ or R₁₁ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₁₁ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₁₁ taken together with R₁₀, Y₁ or Y₂ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

R₁₃ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, heteroarylalkyl independently substituted with one or more Z₁, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR, —

CN, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, or, R₁₃ taken together with Y₃ or Y₄ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

Y₁ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, and heteroarylalkyl independently substituted with one or more Z₁, or Y₁ taken together with R₁, R₁₁ or Y₂ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

Y₂ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, and heteroarylalkyl independently substituted with one or more Z₁, or Y₂taken together with R₁, R₁₁ or Y₁ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

Y₃ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, and heteroarylalkyl independently substituted with one or more Z₁, or Y₃ taken together with R₄, R₅, R₆, R₁₃ or Y₄ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁;

Y₄ is absent, or Y₄ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, and heteroarylalkyl independently substituted with one or more Z₁, or Y₄ taken together with R₄, R₅, R₆, R₁₃ or Y₃ is selected from the group consisting of alkyleno, alkyleno independently substituted with one or more Z₁, heteroalkyleno, heteroalkyleno independently substituted with one or more Z₁, aryleno, aryleno independently substituted with one or more Z₁, heteroaryleno, and heteroaryleno independently substituted with one or more Z₁; and

Z₁ is selected from the group consisting of, —

R, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, —

O and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group.

2. The compound of claim 1 wherein Y₁ is taken together with R₁ or R₁₁ and is C₂ or C₃ alkyleno or alkyleno independently substituted with one or more Z₁, or Y₂ is taken together with R₁ or R₁₁ and is C₂ or C₃ alkyleno or alkyleno independently substituted with one or more Z₁, or Y₃ is taken together with R₄ or R₅ or R₆ or R₁₃ and is C₂ or C₃ alkyleno or alkyleno independently substituted with one or more Z₁, or Y₄ is taken together with R₄ or R₅ or R₆ or R₁₃ and is C₂ or C₃ alkyleno or alkyleno independently substituted with one or more Z₁.

3. The compound of claim 2 wherein the C₂ or C₃ substituted alkyleno is gem disubstituted with C₁ to C₃ alkyl.

4. The compound of claim 3 wherein the C₂ or C₃ substituted alkyleno is gem disubstituted with methyl.

5. The compound of claim 1 wherein R₈ is alkyl independently substituted with one or more substituents selected from the group consisting of halogen, C(O)R, and —

S(O)₂R wherein R is independently selected from the group consisting of —

OH, O-alkyl, —

NH₂, N-alkyl and linking group.

6. The compound of claim 1 wherein R₈ is CF₃.

7. The compound of claim 1 wherein R₈ is

wherein Z₂₆ and Z₂₇ are each independently selected from the group consisting of hydrogen, — OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR,—

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR, —

NC(O)R, R, and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group, and X₁, X₂, X₃, X₄, and X₅ are each independently selected from the group consisting of hydrogen, —

Cl, —

Br and —

F, wherein n and m are integers each independently ranging from 0 to 5.

8. The compound of claim 7 wherein X₁ and X₂ are —

H.

9. The compound of claim 7 wherein X₁, X₂, X₄, and X₅ are each —

F.

10. The compound of claim 1 wherein R₈ is aryl or aryl independently substituted with one or more Z₁.

11. The compound of claim 1 wherein R₈ has the structure

wherein Z₂₁, Z₂₂, Z₂₃, Z₂₄ and Z₂₅ each taken separately are Z₁.

12. The compound of claim 11 wherein Z₂₁, Z₂₂, Z₂₃, Z₂₄ and Z₂₅ are each independently selected from the group consisting of —

H, halogen, C₁ to C₃ alkyl, —

C(O)OR, —

C(O)R, —

S(O)₂OR, —

S(O)₂R, and —

CH₂OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group.

13. The compound of claim 11 wherein one or more of Z₂₁, Z₂₂, Z₂₃, Z₂₄ or Z₂₅ is —

Cl or —

F.

14. The compound of claim 11 wherein Z₂₁ is —

C(O)OH.

15. The compound of claim 11 wherein Z₂₁ is —

C(O)OH and one of Z₂₃ or Z₂₄ is —

C(O)OH.

16. The compound of claim 11 wherein Z₂₂ and Z₂₅ are each —

Cl.

17. The compound of claim 11 wherein Z₂₂, Z₂₃, Z₂₄ and Z₂₅ are each —

F.

18. The compound of claim 11 wherein Z₂₁ is —

S(O)₂OH and one of Z₂₃ or Z₂₄ is —

C(O)OH.

19. The compound of claim 11 wherein Z₂₁ is —

C(O)OR and one of Z₂₂, Z₂₃, or Z₂₄ is linking group.

20. The compound of claim 1 wherein R₈ is selected from the group consisting of

wherein LG is linking group.

21. The compound of claim 1 wherein at least one of Y₁, Y₂, Y₃, or Y₄ taken separately is selected from the group consisting of —

H, alkyl, aryl and arylalkyl.

22. The compound of claim 1 wherein one or more of R₁, R₄, R₅, R₆, R₇, R₉, R₁₀, R₁₁ and R₁₃ is each independently —

S(O)₂OH.

23. The compound of claim 1 wherein one or more of R₁, R₄, R₅, R₆, R₇, R₉, R₁₀, R₁₁ and R₁₃ are each independently —

F or —

Cl.

24. The compound of claim 1 wherein one or more of R₁, R₄, R₅, R₆, R₇, R₉, R₁₀, R₁₁ and R₁₃ is each independently aryl or aryl independently substituted with one or more Z₁.

25. The compound of claim 1 having the structure

wherein LG is linking group.

26. The compound of claim 1 having the structure

wherein LG is linking group.

27. The compound of claim 1 having the structure

wherein R₈ is selected from the group consisting of

wherein LG is linking group.

28. Compounds useful for the synthesis of extended rhodamine compounds having the structures:

wherein Y₁ taken alone is selected from the group consisting of —

H, alkyl, alkyl independently substituted with one or more Z₁, heteroalkyl, heteroalkyl independently substituted with one or more Z₁, aryl, aryl independently substituted with one or more Z₁, heteroaryl, heteroaryl independently substituted with one or more Z₁, arylalkyl, arylalkyl independently substituted with one or more Z₁, heteroarylalkyl, and heteroarylalkyl independently substituted with one or more Z₁; and

Z₁ is selected from the group consisting of, —

R, halogen, —

OS(O)₂OR, —

S(O)₂OR, —

S(O)₂R, —

S(O)₂NR, —

S(O)R, —

OP(O)O₂RR, —

P(O)O₂RR,—

C(O)OR, —

NRR, —

NRRR, —

NC(O)R, —

C(O)R, —

C(O)NRR,—

CN, —

O and —

OR, wherein R is independently selected from the group consisting of —

H, alkyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and linking group.

29. Compounds useful for the synthesis of extended rhodamine compounds having the structures:

30. Compounds useful for the synthesis of extended rhodamine compounds having the structures: