Synthesis and Properties of 7‐Substituted 7‐Deazapurine (Pyrrolo[2,3‐d]pyrimidine) 2′‐Deoxyribonucleosides
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- Abstract
- Table of Contents
- Materials
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- Literature Cited
Abstract
7?Substituted 7?deazapurine (pyrrolo[2,3?d ]pyrimidine) 2??deoxyribonucleosides are synthesized by stereoselective nucleobase anion glycosylation. The introduction of a halogen at C7 is performed regioselectively either on the nucleobase or on the nucleoside. The pK a values of a series of 7?deazapurine 2??deoxyribonucleosides are provided, and fluorescence properties are also discussed.
Keywords: pyrrolo[2,3?d]pyrimidine; 7?deazapurine; 2??deoxyribonucleoside; nucleobase anion glycosylation; stereoselectivity; regioselective halogenation; pKa values; fluorescence; quenching
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- Basic Protocol 1: Preparation of 7‐Substituted 7‐Deazapurine Nucleosides Related to 2′‐Deoxyadenosine and 2′‐Deoxyinosine
- Basic Protocol 2: Preparation of 7‐IODO‐7‐Deazapurine Nucleosides Related to 2′‐Deoxyguanosine and 2′‐Deoxyxanthosine
- Basic Protocol 3: Preparation of 7‐Bromo‐7‐Deaza‐2′‐Deoxyisoguanosine
- Basic Protocol 4: Determination of pKa Values of Nucleosides
- Reagents and Solutions
- Commentary
- Literature Cited
- Figures
- Tables
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Basic Protocol 1: Preparation of 7‐Substituted 7‐Deazapurine Nucleosides Related to 2′‐Deoxyadenosine and 2′‐Deoxyinosine
Materials
Basic Protocol 2: Preparation of 7‐IODO‐7‐Deazapurine Nucleosides Related to 2′‐Deoxyguanosine and 2′‐Deoxyxanthosine
Materials
Basic Protocol 3: Preparation of 7‐Bromo‐7‐Deaza‐2′‐Deoxyisoguanosine
Materials
Basic Protocol 4: Determination of pKa Values of Nucleosides
Materials
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Figure 1.10.1 The structures of selected 7‐deazapurine 2′‐deoxyribonucleosides. Purine and systematic numbering systems are shown in the first two structures. Compounds: S.1 , 7‐deaza‐2′‐deoxyadenosine; S.2 , 7‐deaza‐2′‐deoxyguanosine; S.3 , 2‐amino‐7‐deaza‐2′‐deoxyadenosine; S.4 , 7‐deaza‐2′‐deoxyisoguanosine; S.5 , 7‐deaza‐2′‐deoxyinosine; S.6 , 7‐deaza‐2′‐deoxyxanthosine. References: S.1a (Seela and Kehne, ); S.1b ‐e (Seela and Thomas, ; Seela and Zulauf, ); S.1f (Seela et al., ); S.2a (Winkeler and Seela, ); S.2b‐e (Ramzaeva and Seela, ); S.3a (Seela et al., ); S.3b‐d (Seela and Peng, ); 4a (Seela and Wei, ); S.4b,c (Seela and Peng, ); S.5a (Seela and Menkhoff, ); S.5b ‐d (Ramzaeva et al., ); S.6a (Seela et al., ); and S.6b ‐d (Seela and Shaikh, ). View Image -
Figure 1.10.2 Preparation of 7‐deaza‐7‐iodo‐2′‐deoxyadenosine (S.1d ) and 7‐deaza‐7‐iodo‐2′‐deoxyinosine (S.5d ) is carried out by glycosylation of an iodinated nucleobase. S1.d can then be used in a palladium‐catalyzed Sonogashira cross‐coupling reaction to yield the 7‐alkynyl derivative S.10 (Seela et al., ). TDA‐1, tris[2‐(2‐methoxyethoxy)ethyl]amine; Tol, p ‐toluoyl. View Image -
Figure 1.10.3 Preparation of 7‐iodo‐7‐deaza‐2′‐deoxyguanosine (S.2d ) and 7‐iodo‐7‐deaza‐2′‐deoxyxanthosine (S.6d ) is carried out by iodination of a precursor nucleoside. i ‐Bu2 O, isobutyric anhydride; DMF, N,N ‐dimethylformamide; NIS, N ‐iodosuccinimide. View Image -
Figure 1.10.4 Preparation of 7‐bromo‐7‐deaza‐2′‐deoxyisoguanosine (S.4c ) is carried out by glycosylation of a brominated nucleobase followed by amination at C4 and selective deamination at C2′. NBS, N ‐bromosuccinimide; Piv, pivaloyl; TDA‐1, tris[2‐(2‐methoxyethoxy)ethyl]amine; Tol, p ‐toluoyl. For structure of S.8 , see Figure . View Image -
Figure 1.10.5 Structures of 7‐deazapurine 2′‐deoxyribonucleosides with interesting fluorescence properties. View Image
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Literature Cited
| Literature Cited | |
| Albert, A. and Serjeant, E.P. 1971. Determination of ionization constants by spectrometry. In The Determination of Ionization Constants, pp. 44‐64. Chapman & Hall, London. | |
| Balow, G., Mohan, V., Lesnik, E.A., Johnston, J.F., Monia, B.P., and Acevedo, O.L. 1998. Biophysical and antisense properties of oligodeoxynucleotides containing 7‐propynyl‐ , 7‐iodo‐ and 7‐cyano‐7‐deaza‐2‐amino‐2′‐deoxyadenosines. Nucl. Acids Res. 26:3350‐3357. | |
| Hoffer, M. 1960. α‐Thymidin. Chem. Ber. 93:2777‐2781. | |
| Latimer, L.J. and Lee, J.S. 1991. Ethidium bromide does not fluoresce when intercalated adjacent to 7‐deazaguanine in duplex DNA. J. Biol. Chem. 266:13849‐13851. | |
| LePecq, J.B. and Paoletti, C. 1967. A fluorescent complex between ethidium bromide and nucleic acids. Physical‐chemical characterization. J. Mol. Biol. 27:87‐106. | |
| Kasai, H., Ohashi, Z., Harada, F., Nishimura, S., Oppenheimer, N.J., Crain, P.F., Liehr, J.G., von Minden, D.L., and McCloskey, J.A. 1975. Structure of the modified nucleoside Q isolated from Escherichia coli transfer ribonucleic acid. 7‐(4,5‐cis‐Dihydroxy‐1‐cyclopenten‐3‐ylaminomethyl)‐7‐deazaguanosine. Biochemistry 14:4198‐4208. | |
| Kazimierczuk, Z., Cottam, H.B., Revankar, G.R., and Robins, R.K. 1984. Synthesis of 2′‐deoxytubercidin, 2′‐deoxyadenosine, and related 2′‐deoxynucleosides via a novel direct stereospecific sodium salt glycosylation procedure. J. Am. Chem. Soc. 106:6379‐6382. | |
| Kelley, S.O. and Barton, J.K. 1998. DNA‐mediated electron transfer from a modified base to ethidium: Pi‐stacking as modulator of reactivity. Chem. Biol. 5:413‐425. | |
| Kilpatrick, M.W. and Walker, R.T. 1982. The nucleotide‐sequence of the transfer‐RNA‐met(m) from the archaebacterium thermoplasma‐acidophilum. Zentralbl. Bakteriol. Mikrobiol. Hyg. 1 Abt. Orig. C 3:79‐89. | |
| Li, H., Peng, X., and Seela, F. 2004. Fluorescence quenching of parallel‐stranded DNA bound ethidium bromide: The effect of 7‐deaza‐2′‐deoxyisoguanosine and 7‐halogenated derivatives. Bioorg. Med. Chem. Lett. 14:6031‐6034. | |
| Martin, J.C. (ed.) 1989. Nucleotide Analogues as Antiviral Agents. American Chemical Society, Washington, D.C. | |
| Mizusawa, S., Nishimura, S., and Seela, F. 1986. Improvement of the dideoxy chain termination method of DNA sequencing by use of deoxy‐7‐deazaguanosine triphosphate in place of dGTP. Nucl. Acids Res. 14:1319‐1324. | |
| Prober, J.M., Trainor, G.L., Dam, R.J., Hobbs, F.W., Robertson, C.W., Zagursky, R.J., Cocuzza, A.J., Jensen, M.A., and Baumeister, K. 1987. A system for rapid DNA sequencing with fluorescent chain‐terminating dideoxynucleotides. Science 238:336‐341. | |
| Pudlo, J.S., Nassiri, M.R., Kern, E.R., Wotring, L.L., Drach, J.C., and Townsend, L.B. 1990. Synthesis, antiproliferative, and antiviral activity of certain 4‐substituted and 4,5‐disubstituted 7‐[(1,3‐dihydroxy‐2‐propoxy)methyl]pyrrolo[2,3‐d]pyrimidines. J. Med. Chem. 33:1984‐1992. | |
| Ramzaeva, N. and Seela, F. 1995. 7‐Substituted 7‐deaza‐2′‐deoxyguanosines: Regioselective halogenation of pyrrolo[2,3‐d]pyrimidine nucleosides. Helv. Chim. Acta 78:1083‐1090. | |
| Ramzaeva, N., Mittelbach, C., and Seela, F. 1999. 7‐Halogenated 7‐deaza‐2′‐deoxyinosines. Helv. Chim. Acta 82:12‐18. | |
| Revankar, G.R. and Robins, R.K. 1991. Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) nucleosides. In Chemistry of Nucleosides and Nucleotides (L.B. Townsend, ed.) pp. 200‐247. Plenum, New York. | |
| Rolland, V., Kotera, M., and Lhomme, J. 1997. Convenient preparation of 2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranosyl chloride. Synth. Commun. 27:3505‐3511. | |
| Seela, F. and Becher, G. 2000. Synthesis, base pairing, and fluorescence properties of oligonucleotides containing 1H‐pyrazolo[3,4‐d]pyrimidin‐6‐amine (8‐aza‐7‐deazapurin‐2‐amine) as an analogue of purin‐2‐amine. Helv. Chim. Acta 83:928‐942. | |
| Seela, F. and Driller, H. 1989. 7‐Deaza‐2′‐deoxy‐O6‐methylguanosine: Selective N2‐formylation via a formamidine, phosphoramidite synthesis and properties of oligonucleotides. Nucleosides Nucleotides 8:1‐21. | |
| Seela, F. and Engelke, U. 1985. Ein Purin/7‐Desazapurin‐Dinucleosid‐Monophosphat mit 2‐Amino‐7H‐pyrrolo[2,3‐d]pyrimidin als fluoreszierender Base. Liebigs Ann. Chem. 1175‐1184. | |
| Seela, F. and Kehne, A. 1983. 2′‐Desoxytubercidin: Synthese eines 2′‐Desoxyadenosin‐Isosteren durch Phasentransferglycosylierung. Liebigs Ann. Chem. 876‐884. | |
| Seela, F. and Menkhoff, S. 1985. Synthese von 7‐Desaza‐2′‐desoxyinosin durch Phasentransferglycosylierung. Liebigs Ann. Chem. 1360‐1366. | |
| Seela, F. and Peng, X. 2004. Regioselective syntheses of 7‐halogenated 7‐deazapurine nucleosides related to 2‐amino‐7‐deaza‐2′‐deoxyadenosine and 7‐deaza‐2′‐deoxyisoguanosine. Synthesis 1203‐1210. | |
| Seela, F. and Shaikh, K. 2004. 7‐Halogenated 7‐deaza‐2′‐deoxyxanthine 2′‐deoxyribonucleosides. Helv. Chim. Acta 87:1325‐1332. | |
| Seela, F. and Steker, H. 1984. Synthese von 2′‐desoxyribofuranosiden des 7H‐Pyrrolo[2,3‐d]pyrimidins: Einfluβ des C‐2‐Substituenten auf Fluoreszenz. Liebigs Ann. Chem. 1719‐1730. | |
| Seela, F. and Thomas, H. 1994. Synthesis of certain 5‐substituted 2′‐deoxytubercidin derivatives. Helv. Chim. Acta 77:897‐903. | |
| Seela, F. and Wei, C. 1999. The base‐pairing properties of 7‐deaza‐2′‐deoxyisoguanosine and 2′‐deoxyisoguanosine in oligonucleotide duplexes with parallel and antiparallel chain orientation. Helv. Chim. Acta 82:726‐745. | |
| Seela, F. and Zulauf, M. 1996. Palladium‐catalyzed cross coupling of 7‐iodo‐2′‐deoxytubercidin with terminal alkynes. Synthesis 726‐730. | |
| Seela, F., Driller, H., and Liman, U. 1985. 7‐Desaza‐Isostere von 2′‐Desoxyxanthosin und 2′‐Desoxyspongosin: Synthese via Glycosylierung von 2,4‐Dichlor‐7H‐pyrrolo[2,3‐d]pyrimidin. Liebigs Ann. Chem. 312‐320. | |
| Seela, F., Steker, H., Driller, H., and Bindig, U. 1987. 2‐Amino‐2′‐desoxytubercidin und verwandte Pyrrolo[2,3‐d]pyrimidinyl‐2′‐desoxyribofuranoside. Liebigs Ann. Chem. 15‐19. | |
| Seela, F., Westermann, B., and Bindig, U. 1988. Liquid‐liquid and solid‐liquid phase‐transfer glycosylation of pyrrolo[2,3‐d]pyrimidines: Stereospecific synthesis of 2‐deoxy‐β‐D‐ribofuranosides related to 2′‐deoxy‐7‐carbaguanosine. J. Chem. Soc., Perkin Trans. I 697‐702. | |
| Seela, F., Chen, Y., Bindig, U., and Kazimierczuk, Z. 1994. Synthesis of 2′‐deoxyisoinosine and related 2′‐deoxyribonucleosides. Helv. Chim. Acta 77:194‐202. | |
| Seela, F., Chen, Y., and Sauer, M. 1998. Synthesis of 2′,3′‐didehydro‐2′,3′‐dideoxyisoinosine and oxidation of fluorescent 2‐hydroxypurine nucleosides by xanthine oxidase. Nucleosides Nucleotides 17:39‐52. | |
| Seela, F., Zulauf, M., Sauer, M., and Deimel, M. 2000. 7‐Substituted 7‐deaza‐2′‐deoxyadenosines and 8‐aza‐7‐deaza‐2′‐deoxyadenosines: fluorescence of DNA‐base analogues induced by the 7‐alkynyl side chain. Helv. Chim. Acta 83:910‐927. | |
| Seela, F., Chittepu, P., He, Y., He, J., and Xu, K. 2005. 6‐Azapyrimidine and 7‐deazapurine 2′‐deoxy‐2′‐fluoroarabinonucleosides: Synthesis, conformation and properties of oligonucleotides. Nucleosides Nucleotides Nucleic Acids In press. | |
| Simons, C. 2001. Nucleoside Mimetics: Their Chemistry and Biological Properties. Gordon and Breach Science Publishers, Amsterdam. | |
| Suhadolnik, R.J. 1970. Pyrrolopyrimidine nucleosides. In Nucleoside Antibiotics, pp. 298‐353. Wiley‐Interscience, New York. | |
| Winkeler, H.D. and Seela, F. 1983. Synthesis of 2‐amino‐7‐(2′‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐3,7‐dihydro‐4H‐pyrrolo[2,3‐d]pyrimidin‐4‐one, a new isostere of 2′‐deoxyguanosine. J. Org. Chem. 48:3119‐3122. |
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