Synthesis of DNA using substituted phenylacetyl-protected nucleo

Details Synthesis of DNA using substituted phenylacetyl-protected nucleo Synthesis of DNA using substituted phenylacetyl-protected nucleo

1995-03-01

1997-04-22

Kunz, Gary L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 253, 536 261, C07H 102, C07H 1910, C07H 1920, C07H 2100

Patent

active

056230680

ABSTRACT:
Deoxyribonucleotide and ribonucleotide derivatives of the general formula I ##STR1## wherein R.sup.1 represents --CR'R"--Ar, in which Ar is substituted aryl (as hereinafter defined) and R' and R" are independently selected from the group consisting of hydrogen and lower alkyl; one of --R.sup.2 and R.sup.3 is a hydroxyl-protecting group and the other is a group suitable for synthesis of polynucleotides or for attachment of the nucleotide to a solid support; R.sup.4 is selected from the group consisting of hydrogen, --OH and protected hydroxyl; and B represents a divalent radical corresponding to a purine or pyrimidine base. When synthesis is carried out using these derivatives, the deprotection procedure is reduced to an essentially instantaneous process. The derivatives have acceptable shelf life and are very stable to conventional DNA synthesis conditions. Particularly preferred are those compounds wherein Ar is mono- and dihalo-substituted phenyl.

REFERENCES:
patent: 4415732 (1983-11-01), Caruthers et al.
patent: 4668777 (1987-05-01), Caruthers et al.
patent: 4959463 (1990-09-01), Froehler et al.
patent: 4980460 (1990-12-01), Molko et al.
patent: 5179200 (1993-01-01), Molko et al.
patent: 5204456 (1993-04-01), Molko et al.
Dineva et al. Chem. Abstracts, vol. 120, No. 299197n, 1994, Bioorganic Med. Chem. Lett. 3(12):2781-2784; 1993.
Waldman et al. Sydlett Chem. Abstracts, vol. 120, No. 324101m, (1994) (1):65-7.
Reese et al. "The Protection of Thymine and Guanine Residues in Oligodeoxyribonucleotide Synthesis" J. Chem. Soc. Perkin Trans, 1263-71 (1984).
Schulhof et al., "The Final Deprotection Step In Oligonucleotide Synthesis if Reduced to a Mild and Rapid Ammonia Treatment by Using Labile Base-protecting Groups" Nucleic Acids Research, vol. 15, No. 2, 397-416 (1987).
Sinha et al., "Labile Exocyclic Amine Protection of Nucleosides in DNA, RNA and Oligonucleotide Analog Synthesis Facilitating N-deacylation, Minimizing Depurination and Chain Degradation" Biochimie, 75:13-23 (1993).
Ti et al., "Transient Protection: Efficient One-Flask Synthesis of Protected Deoxynucleosides", J.Am.Chem.Soc., 104: 1316-1319 (1982).
Vu et al., "Fast Oligonucleotide Deprotection Phosphoramidite Chemistry for DNA Synthesis", Tetrahedron Letters, vol. 31, No. 50, 7269-7272 (1990).
Ortigao et al., "Antiesense Effect of Oligodeoxynucleotides with Inverted Terminal Internucleotidic Linkages: A Minimal Modification Protecting against Nucleolytic Degradation" Antisense Research and Development, 2:129-146 (1992).
Agrawal et al., "Oligodeoxynucleoside Methylphosphonates: Synthesis and Enzimic Degradation" Tetrahedron Letters, vol. 28, No. 31, 3539-3542 (1987).
Beaucage et al., "Advances in the Synthesis of Oligonucleotides by the Phosphoramidite Approach" Tetrahedron, vol. 48 No. 12, 2223-2311 (1992).
Frauendorf et al., "Automated Synthesis, Strcutre and Biological Actvity of Backbone-Modified Oligonucleotides, The Antisense Approach", Studies in Natural Products Chemistry, vol. 13 257-294 (1993).
Froehler et al., "Synthesis of DNA via deoxynucleoside H-phosphonate intermediates", Nucleic Acids Research, vol. 14, No. 13, 5399-5407 (1986).
Iyer et al., "3H-1,2-Benzodithiole-3-one 1,1-Dioxide as an Improved Sulfurizing Reagent in the Solid Phase Synthesis of Oligodeoxyribonucleoside Phosphorothioates" J. Am. Chem. Soc., 112, 1253-1254 (1990).
McBride et al., "Amidine Protecting Groups for Oligonucleotide Synthesis" J. Am. Chem. Soc., vol. 108, 2040-2048 (1986).
Scaringe et al., "Chemical Synthesis of biologically active oligoribonucleotides using .beta.-cyanoethyl protected ribonucleoside phosphoramidites" Nucleic Acids Research, vol. 18, No. 18, 5433-5441 (1990).
Kohli et al., "Synthesis of Deoxypolynucleotides--A Novel Protecting Group for Deoxyguanosinte" Indian J. Chem., vol. 18B, 272-273 (1979).
Li et al., "Synthesis and Characterization of Oligodeoxynucleotides Containing 0.sup.6 -Methyl-, 0.sup.6 -Ethyl-, and 0.sup.6 -Isopropylguanine" Biochemistry, vol. 28, 5779-5786 (1989).

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