Aromatic-substituted xanthene dyes

• Main Authors: SCOTT CONRAD BENSON, PETER DAVID THEISEN, KRISHNA GAJANAN UPADHYA, JOAN DALE HAUSER, STEVEN MICHAEL MENCHEN
• Format: Patent
• Language: English
• Published: 23.04.1999
• Edition: 6
• Subjects: ADHESIVES; BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPOSITIONS THEREOF; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; CULTURE MEDIA; DERIVATIVES THEREOF; DYES; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; LAKES; MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FORELSEWHERE; MEASURING; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MISCELLANEOUS APPLICATIONS OF MATERIALS; MISCELLANEOUS COMPOSITIONS; MORDANTS; MUTATION OR GENETIC ENGINEERING; NATURAL RESINS; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES; PAINTS; PHYSICS; POLISHES; PROCESSES OF PREPARING SUCH COMPOSITIONS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; SUGARS; TESTING; VINEGAR; WINE

A class of aromatic-substituted xanthene compounds useful as fluorescent dyes is disclosed, the compounds having general structure (I), where Y1 and Y2 taken separately are selected from the group consisting of hydroxyl, oxygen, imminium, linking group and amine, or Y1 taken together with R2 is cyclic imine, or Y2 taken together with R3 is cyclic amine; R2, R3, R5, and R7 taken separately are selected from the group consisting of hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, imminium, amido, nitrile, lower alkoxy, phenyl, and linking group; R1 taken separately is selected from the group consisting of phenyl, substituted phenyl, polycyclic aromatic, substituted polycyclic aromatic, linking-group and electron-rich heterocycle, or when taken together with R7 is selected from the group consisting of electron-rich heterocycle and indene; R4 taken separately is selected from the group consisting of amino, amido, phenyl, substituted phenyl, polycyclic aromatic, substituted polycyclic aromatic, indene, linking group and electron-rich heterocycle, or when taken together with R5 is selected from the group consisting of phenyl, substituted phenyl, polycyclic aromatic, substituted polycyclic aromatic, indene, and electron rich heterocycle; and R6 is selected from the group consisting of acetylene, lower alkyl, lower alkene, cyano, phenyl, substituted phenyl, and heterocyclic aromatic. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates. In yet another aspect, the present invention includes reagents labelled with the asymmetric benzoxanthene dye compounds, including deoxynucleotides, dideoxynucleotides, phosphoramidites, and polynucleotides. In an additional aspect, the invention includes methods utilising such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.