Protection of 5′‐Hydroxy Functions of Nucleosides

H. Seliger1

1 University of Ulm, Ulm, Germany
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 2.3
DOI:  10.1002/0471142700.nc0203s00
Online Posting Date:  May, 2001
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The 5‐hydroxy group is the primary hydroxy group of nucleosides. It is mandatory to protect 5‐hydroxyls in all methods of oligonucleotide synthesis that require nucleoside synthons. This unit discusses a wide variety of acid‐labile and base‐labile protecting groups, as well as enzymatic methods for 5‐protection and deprotection.

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Table of Contents

  • Scope of this Overview
  • Acid‐Labile Protecting Groups
  • Blocking Groups Labile to Nonacidic Conditions
  • Enzymatic Methods for 5′‐Hydroxyl Protection and Deprotection
  • Protection of 5′‐Hydroxy Functions: Remaining Problems, Considerations, and Options
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

Literature Cited
   Adams, S.P., Kavka, K.S., Wykes, E.J., Holder, S.B., and Galluppi, G.R. 1983. Hindered dialkylamino nucleoside phosphite reagents in the synthesis of two DNA 51‐mers. J. Am. Chem. Soc. 105:661‐663.
   Andersen, W., Hayes, D.H., Michelson, A.M., and Todd, A.R. 1954. Deoxyribonucleosides and related compounds. Part IV. The configuration at the glycosidic centre in deoxyadenosine and deoxycytidine. J. Chem. Soc. 1882‐1887.
   Andrus, A., Efcavitch, J.W., McBride, L.J., and Giusti, B. 1988. Novel activating and capping reagents for improved hydrogen‐phosphonate DNA synthesis. Tetrahedron Lett. 29:861‐864.
   Atkinson, T. and Smith, M. 1984. Solid‐phase synthesis of oligodeoxyribonucleotides by the phosphate triester method. In A Practical Approach to Oligonucleotide Synthesis (M.J. Gait, ed.) pp. 35‐81. IRL Press, Oxford.
   Balgobin, N. and Chattopadhyaya, J.B. 1982a. Two sulfur containing protecting groups for alcoholic hydroxyl function. Chem. Scr. 19:143‐144.
   Balgobin, N. and Chattopadhyaya, J.B. 1982b. An efficient chemical synthesis of a biologically functional DNA molecule, 5′d(A‐T‐G‐G‐G‐T‐T‐T‐C‐T‐T‐C‐G‐C‐)3′, through the phospho‐triester approach. Chem. Scr. 20:133‐138.
   Balgobin, N. and Chattopadhyaya, J. 1987. Solid phase synthesis of DNA under a non‐depurinating condition with a base labile 5′‐protecting group (Fmoc) using phosphiteamidite approach. Nucleosides Nucleotides 6:461‐463.
   Balgobin, N., Josephson, S., and Chattopadhyaya, J.B. 1981a. The 2‐phenylsulfonylethylcarbonyl (PSEC) group for the protection of the hydroxyl function. Tetrahedron Lett. 22:3667‐3670.
   Balgobin, N., Josephson, S., and Chattopadhyaya, J.B. 1981b. A general approach to the chemical synthesis of oligodeoxyribonucleotides. Acta Chem. Scand. B 35:201‐212.
   Bannwarth, W. and Wippler, J. 1990. A new combined purification/phosphorylation procedure for oligodeoxynucleotides. Helv. Chim. Acta 73:1139‐1147.
   Bazin, H., Heikkilä, J., and Chattopadhyaya, J. 1985. Some aspects of the reaction of arenesulfenyl chlorides with hydroxyl functions of ribonucleosides. Acta Chem. Scand. B 39:391‐400.
   Beaucage, S.L. and Iyer, R.P. 1992. Advances in the synthesis of oligonucleotides by the phosphoramidite approach. Tetrahedron 48:2223‐2311.
   Beaucage, S.L. and Iyer, R.P. 1993. The synthesis of modified oligonucleotides by the phosphoramidite approach and their applications. Tetrahedron 49:6123‐6194.
   Belagaje, R. and Brush, C.K. 1982. Polymer supported synthesis of oligonucleotides by a phosphotriester method. Nucl. Acids Res. 10:6295‐6303.
   Bergmann, F. and Pfleiderer, W. 1994a. The 2‐dansylethoxycarbonyl (= 2‐{[5‐(dimethyl‐amino)naphthalen‐1‐yl]sulfonyl}ethoxycarbonyl; Dnseoc) group for protection of the 5′‐hydroxy function in oligodeoxyribonucleotide synthesis. Helv. Chim. Acta 77:203‐215.
   Bergmann, F. and Pfleiderer, W. 1994b. The 2‐dansylethoxycarbonyl (= 2‐{[5‐(dimethyl‐amino)naphthalen‐1‐yl]sulfonyl}ethoxycarbonyl; Dnseoc) group for protection of the 5′‐hydroxy function in oligoribonucleotide synthesis. Helv. Chim. Acta 77:481‐501.
   Bergmann, F. and Pfleiderer, W. 1994c. Solid‐phase synthesis of oligoribonucleotides using the 2‐dansylethoxycarbonyl (= 2‐{[5‐(dimethyl‐amino)naphthalen‐1‐yl]sulfonyl}ethoxycarbonyl; Dnseoc) group for 5′‐hydroxy protection. Helv. Chim. Acta 77:988‐998.
   Berner, S., Mühlegger, K., and Seliger, H. 1989. Studies on the role of tetrazole in the activation of phosphoramidites. Nucl. Acids Res. 17:853‐864.
   Bessodes, M., Komiotis, D., and Antonakis, K. 1986. Rapid and selective detritylation of primary alcohols using formic acid. Tetrahedron. Lett. 27:579‐580.
   Biernat, J., Wolter, A., and Köster, H. 1983. Purification oriented synthesis of oligodeoxynucleotides in solution. Tetrahedron. Lett. 24:751‐754.
   Birch‐Hirschfeld, E., Weiss, R., Rosenthal, A., and Cech, D. 1983. Festphasensynthese von Oligodesoxyribonucleotiden an Polystyren‐Teflon‐Trägern nach der Diestermethode. J. Prakt. Chem. 325:133‐142.
   Brown, J.M., Christodoulou, C., Reese, C.B., and Sindona, G. 1984. Two new protected acyl protecting groups for alcoholic hydroxy functions. J. Chem. Soc. Perkin Trans. 1. 1785‐1790.
   Brown, J.M., Christodoulou, C., Jones, S.S., Modak, A.S., Reese, C.B., Sibanda, S., and Ubasawa, A. 1989a. Synthesis of the 3′‐terminal half of yeast alanine transfer ribonucleic acid (tRNAAla) by the phosphotriester approach in solution. Part 1. Preparation of the nucleoside building blocks. J. Chem. Soc. Perkin Trans. 1. 1735‐1750.
   Brown, J.M., Christodoulou, C., Modak, A.S., Reese, C.B., and Serafinowska, H.T. 1989b. Synthesis of the 3′‐terminal half of yeast alanine transfer ribonucleic acid (tRNAAla) by the phosphotriester approach in solution. Part 2. J. Chem. Soc. Perkin Trans. 1. 1751‐1767.
   Bühler, S., Giegrich, H., and Pfleiderer, W. 1999. New photolabile protecting groups of the 2‐(2‐nitrophenyl)ethoxycarbonyl and the 2‐(2‐nitro‐phenyl)ethylsulfonyl type for the oligonucleotide synthesis. Nucleosides Nucleotides 8:1281‐1283.
   Caruthers, M.H. 1982. Chemical synthesis of oligodeoxynucleotides using the phosphite triester intermediates. In Chemical and Enzymatic Synthesis of Gene Fragments: A Laboratory Manual (H.G. Gassen and A. Lang, eds.) pp. 71‐79. Verlag Chemie, Weinheim, Germany.
   Caruthers, M.H. 1998. Synthesis of DNA, RNA, and various new analogs on polymer supports. Lecture, 8th International Conference on Polymer‐Based Technology, Ma'ale Hachamisha, Israel.
   Caruthers, M.H., Dellinger, D., and Prosser, K. 1986. Nucleic acid synthesis and applications to molecular biology. Chem. Scr. 26:25‐30.
   Caruthers, M.H., Wyrzikiewicz, T., and Dellinger, D.J. 1994. Synthesis of oligonucleotides and oligonucleotide analogs on polymer supports. In Innovation and Perspectives in Solid Phase Synthesis (R. Epton ed.) pp. 39‐44. Mayflower, Birmingham, U.K.
   Chaix, C., Molko, D., and Teoule, R. 1989. The use of labile base protecting groups in oligoribonucleotide synthesis. Tetrahedron Lett. 30:71‐74.
   Chattopadhyaya, J.B. 1980. Synthesis of adenylyl‐(2′‐5′)‐adenylyl‐(2′‐5′)‐adenosine (2‐5A core). Tetrahedron Lett. 21:4113‐4116.
   Chattopadhyaya, J.B. and Reese, C.B. 1978. The 9‐phenylxanthen‐9‐yl protecting group. J. Chem. Soc., Chem. Commun. 639‐640.
   Chattopadhyaya, J.B. and Reese, C.B. 1980. Chemical synthesis of a tridecanucleoside dodecaphosphate sequence of SV40 DNA. Nucl. Acids Res. 8:2039‐2053.
   Chattopadhyaya, J.B., Reese, C.B., and Todd, A.H. 1979. 2‐Dibromomethylbenzoyl: An acyl protecting group removable under exceptionally mild conditions. J. Chem. Soc. Chem. Commun. 987‐988.
   Chaudhary, S.K. and Hernandez, O. 1979. 4‐Dimethylaminopyridine: An efficient and selective catalyst for the silylation of alcohols. Tetrahedron Lett. 20:99‐102.
   Christodoulou, C. and Reese, C.B. 1983. Dealkylation of nucleoside arylmethyl 2‐chlorophenyl phosphates: The 2,4‐dinitrobenzyl protecting group. Tetrahedron Lett. 24:951‐954.
   Christodoulou, C., Agrawal, S., and Gait, M.J. 1987a. A new 5′‐protecting group for use in the solid‐phase synthesis of oligoribonucleotides. Nucleosides Nucleotides 6:341‐344.
   Christodoulou, C., Agrawal, S., and Gait, M.J. 1987b. Progress towards solid‐phase synthesis of oligoribonucleotides. In Biophosphates and Their Analogues—Synthesis, Structure, Metabolism and Activity (K.S. Bruzik and W.J. Stec eds.) pp 99‐106. Elsevier/North‐Holland, Amsterdam.
   Corey, E.J., Gras, J.‐L., and Ulrich, P. 1976. A new general method for the protection of the hydroxyl function. Tetrahedron Lett. 11:809‐812.
   Dellinger, D.J., Wyrzkewicz, T.K., Betley, J.R., and Caruthers, M.H. 1998. Solid‐phase synthesis of oligodeoxyribonucleotides using phosphoramidite synthons in a two step synthesis cycle. XIIIth International Round Table: Nucleosides, Nucleotides and their Biological Applications Montpellier. Poster 209.
   Engels, J. 1979. Selektive elektrochemische Schutzgruppenabspaltung in der Nucleotidsynthese. Angew. Chem. 91:155‐156
   Fearon, K.L., Stults, J.T., Bergot, B.J., Christensen, L.M., and Raible, A.M. 1995. Investigation of the ‘n‐1’ impurity in phosphorothioate oligodeoxynucleotides synthesized by the solid‐phase β‐cyanoethyl phosphoramidite method using stepwise sulfurization. Nucl. Acids Res. 23:2754‐2761.
   Fersht, A.R. and Jencks, W.P. 1970. The acetylpyridinium ion intermediate in pyridine‐catalyzed hydrolysis and acyl transfer reactions of acetic anhydride. Observation, kinetics, structure‐reactivity correlations, and effects of concentrated salt solutions. J. Am. Chem. Soc. 92:5432‐5442.
   Fisher, E.F. and Caruthers, M.H. 1983. Color coded triarylmethyl protecting groups useful for deoxypolynucleotide synthesis. Nucl. Acids Res. 11:1589‐1599.
   Fodor, S.P.A., Read, J.L., Pirrung, M.C., Stryer, L., Lu, A.T., and Solas, D. 1991. Light‐directed, spatially addressable parallel chemical synthesis. Science 251:767‐773.
   Földes‐Papp, Z., Birch‐Hirschfeld, E., Eickhoff, H., Baumann, G., Peng, W.‐G., Biber, T., Seydel, R., Kleinschmidt, A.K., and Seliger, H. 1996. Fractals for multicyclic synthesis conditions of biopolymers; examples of oligonucleotide synthesis measured by high‐performance capillary electrophoresis and ion‐exchange high‐performance liquid chromatography. J. Chromatogr. 739:431‐447.
   Földes‐Papp, Z., Baumann, G., Birch‐Hirschfeld, E., Eickhoff, H., Greulich, K.O., Kleinschmidt, A.K., and Seliger, H. 1998. The analysis of oligonucleotide preparations by fractal measures. Biopolymers 45:361‐379.
   Fourrey, J.L., Varenne, J., Blonski, C., Dousset, P., and Shire, D. 1987. 1,1‐Bis‐(4‐methoxyphenyl)‐1′‐pyrenyl methyl (bmpm): A new fluorescent 5′ protecting group for the purification of unmodified and modified oligonucleotides. Tetrahedron Lett. 28:5157‐5160.
   Fritz, H.‐J., Frommer, W.‐B., Kramer, W., and Werr, W. 1982. Simplified preparations of blocked 2′‐deoxyribonucleosides as starting materials for chemical oligonucleotide synthesis. In Chemical and Enzymatic Synthesis of Gene Fragments: A Laboratory Manual (H.G. Gassen and A. Lang eds.) pp. 43‐52. Verlag Chemie, Weinheim, Germany.
   Fuentes, J., Cuevas, T., and Pradera, M.A. 1994. A mild and efficient detritylation of some carbohydrate derivatives. Synth. Commun. 24:2237‐2245.
   Fukuda, T., Hamana, T., and Marumoto, R. 1988. Synthesis of RNA oligomer using 9‐fluorenylmethoxycarbonyl (Fmoc) group for 5′‐hydroxyl protection. Nucl. Acids Res. Symp. Ser. 19:13‐16.
   Furukawa, H., Momota, K., Agatsuma, T., Yamamoto, I., Kimura, S., and Shimada, K. 1994. Mechanism of inhibition of HIV‐1 infection in vitro by guanine‐rich oligonucleotides modified at the 5′ terminal by dimethoxytrityl residue. Nucl. Acids Res. 22:5621‐5627.
   Gaffney, B.L. and Jones, R.A. 1982a. Synthesis of O‐6‐alkylated deoxyguanosine nucleosides. Tetrahedron Lett. 23:2253‐2256.
   Gaffney, B.L. and Jones, R.A. 1982b. A new strategy for the protection of deoxyguanosine during oligonucleotide synthesis. Tetrahedron Lett. 23:2257‐2260.
   Gaffney, B.L. and Jones, R.A. 1988. Large‐scale oligonucleotide synthesis by the H‐phosphonate method. Tetrahedron Lett. 29:2619‐2622.
   Gaffney, B.L., Marky, L.A., and Jones, R.A. 1984. The influence of the purine 2‐amino group on DNA conformation and stability. II. Synthesis and physical characterization of d(CGT(2‐NH2)ACG), d(CGU(2‐NH2)ACG), and d(CGT(2‐NH2)AT(2‐NH2)ACG). Tetrahedron 40:3‐13.
   Gait, M.J., Matthes, H.W.D., Singh, M., Sproat, B.S., and Titmas, R.C. 1982. Synthesis of oligodeoxyribonucleotides by a continuous flow, phosphotriester method on a kieselgur/polyamide support. In Chemical and Enzymatic Synthesis of Gene Fragments: A Laboratory Manual (H.G. Gassen and A. Lang eds.) pp. 1‐42. Verlag Chemie, Weinheim, Germany.
   Garcia‐Alles, L.F. and Gotor, V. 1995. Synthesis of 5′‐O‐ and 3′‐O‐nucleoside carbamates. Tetrahedron 51:307‐316.
   Garcia‐Alles, L.F., Moris, F., and Gotor, V. 1993. Chemo‐enzymatic synthesis of 2′‐deoxynucleoside urethanes. Tetrahedron. Lett. 34:6337‐6338.
   Gildea, B.D., Coull, J.M., and Köster, H. 1990. A versatile acid‐labile linker for modification of synthetic biomolecules. Tetrahedron. Lett. 31:7095‐7098.
   Gilham, P.T. and Khorana, H.G. 1958. Studies on Polynucleotides. I. A new and general method for the chemical synthesis of the C5′‐C3′ internucleotidic linkage. Syntheses of deoxyribo‐dinucleotides. J. Am. Chem. Soc. 80:6212‐6222.
   Gioeli, C. and Chattopadhyaya, J.B. 1982. The fluoren‐9‐ylmethoxycarbonyl group for the protection of hydroxy‐groups; its application in the synthesis of an octathymidylic acid fragment. J. Chem. Soc. Chem. Commun. 672‐673.
   Gioeli, C., Balgobin, N., Josephson, S., and Chattopadhyaya, J.B. 1981. 2‐(Trimethylsilyl)ethyl chloroformate: A convenient reagent for protection of hydroxyl function. Tetrahedron Lett. 22:969‐972.
   Görtz, H.‐H. and Seliger, H. 1981. New hydrophobic protecting groups for the chemical synthesis of oligonucleotides. Angew. Chem. Int. Ed. Engl. 20:681‐683.
   Grams, G.W. and Letsinger, R.L. 1968. N6,3′‐O‐Disubstituted deoxyadenosine. J. Org. Chem. 33:2589‐2590.
   Grams, G.W. and Letsinger, R.L. 1970. Synthesis of a diribonucleoside monophosphate by the β‐cyanoethyl phosphotriester method. J. Org. Chem. 35:868‐870.
   Guo, Z., Pfundheller, H.M., and Sanghvi, Y. 1998. A process for the capture and reuse of DMT group during manufacturing of oligonucleotides. Abstracts XIIIth International Round Table: Nucleosides, Nucleotides and their Biological Applications, Montpellier. Poster 194.
   Gupta, K.C., Gaur, R.K., and Sharma, P. 1991. Use of the 4‐methoxy‐4′‐octyloxytrityl group as an affinity handle for the purification of synthetic oligonucleotides. J. Chromatogr. 541:341‐348.
   Guzaev, A., Salo, H., Azhayev, A., and Lönnberg, H. 1995. A new approach for chemical phosphorylation of oligonucleotides at the 5′‐terminus. Tetrahedron 51:9375‐9384.
   Habus, I. and Agrawal, S. 1994. Improvement in the synthesis of oligonucleotides of extended length by modification of detritylation step. Nucl. Acids Res. 22:4350‐4351
   Happ, E. and Scalfi‐Happ, C. 1988. New trityl‐based protecting groups with a mild two‐step removal. Nucleosides Nucleotides 7:813‐816.
   Hasan, A., Stengele, K.‐P., Giegrich, H., Cornwell, P., Isham, K.R., Sachleben, R.A., Pfleiderer, W., and Foote, R.S. 1997. Photolabile protecting groups for nucleosides: Synthesis and photodeprotection rates. Tetrahedron 53:4247‐4264.
   Hirao, I., Koizumi, M., Ishido, Y., and Andrus, A. 1998. 1,1,3,3‐Tetraisopropyl‐3‐(2‐(triphenylmethoxy)ethoxy)disiloxane‐1‐yl group, a potential 5′‐O‐protecting group for solid‐phase RNA synthesis. Tetrahedron Lett. 39:2989‐2992.
   Horn, T. and Urdea, M.S. 1985. Enzymatic purification of chemically synthesized oligodeoxyribonucleotides prior to removal from a solid‐support. Nucl. Acids Res. Symp. Ser. 16:153‐156.
   Hosaka, H., Suzuki, Y., Gug‐Kim, S., and Takaku, H. 1991. A convenient approach to the synthesis of medium size deoxyribooligonucleotides by improved new phosphite method. Tetrahedron Lett. 32:785‐788.
   Hotoda, H., Momota, K., Furukawa, H., Nakamura, T., and Kaneko, M. 1994. Biologically active oligodeoxyribonucleotides. II. Structure activity relationships of anti‐HIV‐1 pentadecadeoxyribonucleotides bearing 5′‐end‐modifications. Nucleosides Nucleotides 13:1375‐1395.
   Itakura, K., Rossi, J.J., and Wallace, R.B. 1984. Synthesis and use of synthetic oligonucleotides. Annu. Rev. Biochem. 53:323‐356.
   Ito, H., Ike, Y., Ikuta, S., and Itakura, K. 1982. Solid phase synthesis of polynucleotides. VI. Further studies on polystyrene copolymers for the solid support. Nucl. Acids Res. 10:1755‐1769.
   Iwai, S. and Ohtsuka, E. 1988. 5′‐Levulinyl and 2′‐tetrahydrofuranyl protection for the synthesis of oligoribonucleotides by the phosphoramidite approach. Nucl. Acids Res. 16:9443‐9456.
   Iwai, S., Sasaki, T., and Ohtsuka, E. 1990. Large scale synthesis of oligoribonucleotides on a solid support: Synthesis of a catalytic RNA duplex. Tetrahedron 46:6673‐6688.
   Iyer, R.P., Jiang, Z., Yu, D., Tan, W., and Agrawal, S. 1995. Improved procedure for the detritylation of DMT‐oligonucleotides: Use of Dowex. Synth. Commun. 25:3611‐3623.
   Josephson, S. and Chattopadhyaya, J.B. 1981. The application of the 2‐phenylsulfonylethyl‐, a novel phosphate protecting group, in the synthesis of DNA fragments of defined sequences. Chem. Scr. 18:184‐188.
   Kamaike, K., Takahashi, M., Utsugi, K., Tomizuka, K., and Ishido, Y. 1995. An efficient method for the synthesis of [4‐15N]cytidine and [6‐15N]adenosine derivatives from uridine and inosine. Tetrahedron Lett. 36:91‐94.
   Kamaike, K., Takahashi, M., Utsugi, K., Tomizuka, K., Okazaki, Y., Tamada, Y., Kinoshita, K., Masuda, H., and Ishido, Y. 1996. An efficient method for the synthesis of [4‐15N]cytidine, 2′‐deoxy[4‐15N]cytidine, [6‐15N]adenosine, and 2′‐deoxy[6‐15N]adenosine derivatives. Nucleosides Nucleotides 15:749‐769.
   Kamaike, K., Takahashi, H., Kakinuma, T., Morohoshi, K., and Ishido, Y. 1997. Oligonucleotide synthesis by the use of a 2‐(levulinyloxymethyl)‐5‐nitrobenzoyl group as the novel base‐labile protecting group for the 5′‐hydroxyl groups of ribonucleoside and 2′‐deoxyribonucleoside 3′‐phosphoramidites. Tetrahedron Lett. 38:6857‐6860.
   Karl, R.M., Klösel, R., König, S., Lehnhoff, S., and Ugi, I. 1995. 1,1‐Dianisyl‐2,2,2‐trichlorethyl ethers—a new protection for the hydroxyl group. Tetrahedron Lett. 51:3759‐3766.
   Karl, R.M., Richter, W., Klösel, R., Mayer, M., and Ugi, I. 1996. The 1,1‐dianisyl‐2,2,2‐trichloroethyl moiety as a new protective group for the synthesis of dinucleoside trifluoromethylphosphonates. Nucleosides Nucleotides 15:379‐386.
   Kaufmann, G., Fridkin, M., Zutra, A., and Littauer, U. 1971. Monofunctional substrates of polynucleotide phosphorylase. The monoaddition of 2′(3′)‐O‐isovaleryl‐nucleoside diphosphate to an initiator oligonucleotide. Eur. J. Biochem. 24:4‐11.
   Kawashima, E., Aoyama, Y., Sekine, T., Miyahara, M., Radwan, M.F., Nakamura, E., Kainosho, M., Kyogoku, Y., and Ishido, Y. 1995. Sonochemical and triethylborane‐induced tin deuteride reduction for the highly diastereoselective synthesis of (2′R)‐2′‐deoxy[2′‐2H]ribonucleoside derivatives. J. Org. Chem. 60:6980‐6986.
   Kawashima, E., Toyama, K., Ohshima, K., Kainosho, M., Kyogoku, Y., and Ishido, Y. 1997. Novel approach to diastereoselective synthesis of 2′‐deoxy[ 5′‐2H1]ribonucleoside derivatives by reduction of the corresponding 5′‐O‐acetyl‐2′‐deoxy‐5′‐phenylselenoribonucleoside derivatives with a Bu3Sn2H‐Et3B system. Chirality 9:435‐442.
   Kierzek, R., Ito, H., Bhatt, R., and Itakura, K. 1981. Selective N‐deacylation of N,O‐protected nucleosides by zinc bromide. Tetrahedron Lett. 22:3761‐3764.
   Klösel, R. König, S. and Lehnhoff, S. 1996. The 1,1‐dianisyl‐2,2,2‐trichloroethyl group as 2′‐hydroxyl protection of ribonucleotides. Tetrahedron 52:1493‐1502.
   Kohli, V., Blöcker, H., and Köster, H. 1980. The triphenylmethyl (trityl) group and its uses in nucleotide chemistry. Tetrahedron Lett. 21:2683‐2686.
   Kössel, H. and Seliger, H. 1975. Recent advances in polynucleotide synthesis. Fortschr. Chem. Org. Naturst. 32:297‐508.
   Köster, H. and Sinha, N.D. 1982. Dialkyl aluminium chloride: A reagent for removal of trityl group from trityl ethers of deoxynucleosides, deoxynucleotides, and oligodeoxynucleotides. Tetrahedron Lett. 23:2641‐2644.
   Köster, H., Stumpe, A., and Wolter, A. 1983. Polymer support oligonucleotide synthesis 13: Rapid and efficient synthesis of oligodeoxynucleotides on porous glass support using triester approach. Tetrahedron Lett. 24:747‐750.
   Köster, H., Biernat, J., McManus, J., Wolter, A., Stumpe, A., Narang, C.K., and Sinha, N.D. 1984. Polymer support oligonucleotide synthesis. XV. Synthesis of oligodeoxynucleotides on controlled pore glass (CPG) using phosphate and a new phosphite triester approach. Tetrahedron 40:103‐112.
   Kotschi, U. 1987. Präparative und apparative Beiträge zur Festphasensynthese von Nucleinsäure‐Fragmenten. Dissertation, University of Ulm, Germany.
   Krotz, A.H., Cole, D.L., and Ravikumar, V.T. 1999. Dimethoxytrityl removal in organic medium: Efficient oligonucleotide synthesis without chlorinated solvents. Nucleosides Nucleotides 18:1207‐1209.
   Kwiatkowski, M. and Chattopadhyaya, J. 1984. The 9‐(4‐octadecyloxyphenyl‐xanthen)‐9‐yl‐group. A new acid‐labile hydroxyl protective group and its application in the preparative reverse‐phase chromatographic separation of oligoribonucleotides. Acta Chem. Scand. B 38:657‐671.
   Kwiatkowski, M., Heikkilä, S., Björkman, S., and Chattopadhyaya, J.B. 1983. Chemical synthesis of an undecaribonucleoside decaphosphate constituting the 3′‐terminal acceptor stem sequence of yeast tRNAPhe. Chem. Scripta 22:30‐48.
   Lakshman, M.K. and Zajc, B. 1996. A rapid, high‐yield method for 5′‐hydroxyl protection in very reactive and amino group modified nucleosides using dimethoxytrityl tetrafluoroborate. Nucleosides Nucleotides 15:1029‐1039.
   Lehmann, C., Xu, Y‐Z., Christodoulou, C., Tan, Z.‐K., and Gait, M.J. 1989. Solid‐phase synthesis of oligoribonucleotides using 9‐fluorenylmethoxycarbonyl (Fmoc) for 5′‐hydroxyl protection. Nucl. Acids Res. 17:2379‐2390.
   Leonard, N.J. and Neelima. 1995. 1,1,1,3,3,3‐Hexafluoro‐2‐propanol for the removal of the 4,4′‐dimethoxytrityl protecting group from the 5′‐hydroxyl of acid‐sensitive nucleosides and nucleotides. Tetrahedron Lett. 36:7833‐7836.
   Letsinger, R.L. and Finnan, J.L. 1975. Selective deprotection by reductive cleavage with radical anions. J. Am. Chem. Soc. 97:7197‐7198.
   Letsinger, R.L. and Miller, P.S. 1969. Protecting groups for nucleosides used in synthesizing oligonucleotides. J. Am. Chem. Soc. 91:3356‐3359.
   Letsinger, R.L. and Ogilvie, K.K. 1967. Use of p‐nitrophenyl chloroformate in blocking hydroxyl groups in nucleosides. J. Org. Chem. 32:296‐300.
   Letsinger, R.L., Fontaine, J., Mahadevan, V., Schexnayder, D.A., and Leone, R.E. 1964. 2,4‐Dinitrobenzenesulfenyl as a blocking group for hydroxyl functions in nucleosides. J. Org. Chem. 29:2615‐2618.
   Letsinger, R.L., Caruthers, M.H., Miller, P.S., and Ogilvie, K.K. 1967. Oligonucleotide syntheses utilizing β‐benzoylpropionyl, a blocking group with a trigger for selective cleavage. J. Am. Chem. Soc. 89:7146‐7147.
   Luzzio, F.A. and Menes, M.E. 1994. A facile route to pyrimidine‐based nucleoside olefins: Application to the synthesis of d4T (stavudine). J. Org. Chem. 59:7267‐7272.
   Ma, Y. and Sonveaux, E. 1987. The 9‐fluorenylmethyloxycarbonyl (Fmoc) group as a 5′‐O base labile protecting group in solid supported oligonucleotide synthesis. Nucleosides Nucleotides 6:491‐493.
   Ma, Y. and Sonveaux, E. 1989. The 9‐fluorenylmethyloxycarbonyl group as a 5′‐OH protection in oligonucleotide synthesis. Biopolymers 28:965‐973.
   Mairanovsky, V.G. 1976. Elektro‐deblockierung—elektrochemische Abspaltung von Schutzgruppen. Angew. Chem. 9:283‐294.
   Markiewicz, W.T. 1979. Tetraisopropyldisiloxane‐1,3‐diyl, a group for simultaneous protection of 3′‐ and 5′‐hydroxy functions of nucleosides. J. Chem. Res. Miniprint. 0181‐0197.
   Markiewicz, W.T. 1980. The reaction of 1,3‐dichloro‐1,1,3,3,‐tetraisopropyldisiloxane with some open chain polyhydroxy compounds. Tetrahedron Lett. 21:4523‐4524.
   Matsuda, A., Inada, M., Nara, H., Ohtsuka, E., and Ono, A. 1993. Nucleosides and nucleotides. 126. Incorporation of a mutagenic nucleoside, 5‐formyl‐2′‐deoxyuridine, into an oligodeoxyribonucleotide. Bioorg. Med. Chem. Lett. 3:2751‐2754.
   Matteucci, M.D. and Caruthers, M.H. 1980. The use of zinc bromide for removal of dimethoxytrityl ethers from deoxynucleotides. Tetrahedron Lett. 21:3243‐3246.
   Matteucci, M.D. and Caruthers, M.H. 1981. Synthesis of deoxyoligonucleotides on a polymer support. J. Am. Chem. Soc. 103:3185‐3191.
   McEldoon, W.L. and Wiemer, D.F. 1995. Synthesis of nucleoside 3′‐phosphonates via 3′‐keto nucleosides. Tetrahedron 51:7131‐7148.
   McGall, G.H., Labadie, J., Brock, P., Wallraff, G., Nguyen, T., and Hinsberg, W. 1996. Light‐directed synthesis of high‐density oligonucleotide arrays using semiconductor photoresists. Proc. Natl. Acad. Sci. U.S.A. 93:13555‐13560.
   McGall, G.H., Barone, A.D., Diggelmann, M., Fodor, S.P.A., Gentalen, E., and Ngo, N. 1997. The efficiency of light‐directed synthesis of DNA arrays on glass substrates. J. Am. Chem. Soc. 119:5081‐5090.
   Misetic, A. and Boyd, M.K. 1998. The pixyl (Px) group: A novel photocleavable protecting group for primary alcohols. Tetrahedron Lett. 39:1653‐1656.
   Mitchell, M.J., Hirschowitz, W., Rastinejad, F., and Lu, P. 1990. Boron trifluoride‐methanol complex as a non‐depurinating detritylating agent in DNA synthesis. Nucl. Acids. Res. 18:5321.
   Moris, F. and Gotor, V. 1992a. A novel and convenient route to 3′‐carbonates from unprotected 2′‐deoxynucleosides through an enzymatic reaction. J. Org. Chem. 57:2490‐2492.
   Moris, F. and Gotor, V. 1992b. Lipase‐mediated alkoxycarbonylation of nucleosides with oxime carbonates. Tetrahedron 48:9869‐9876.
   Moris, F. and Gotor, V. 1993. A useful and versatile procedure for the acylation of nucleosides through an enzymatic reaction. J. Org. Chem. 58:653‐660.
   Mullah, B. and Andrus, A. 1996. Purification of 5′‐O‐trityl‐on oligoribonucleotides. Investigation of phosphate migration during purification and detritylation. Nucleosides Nucleotides 15:419‐430.
   Natt, F. and Häner, R. 1997. Lipocap: A lipophilic phosphoramidite‐based capping reagent. Tetrahedron 53:9629‐9636.
   Nozaki, K., Uemura, A., Yamashita, J., and Yasumoto, M. 1990. Enzymatic regioselective acylation of the 3′‐hydroxyl groups of 2′‐deoxy‐5‐fluorouridine (FUdR) and 2′‐deoxy‐5‐trifluoromethyluridine (CF3UdR). Tetrahedron Lett. 31:7327‐7328.
   Ogilvie, K.K. and Letsinger, R.L. 1967. Use of isobutyloxycarbonyl as a blocking group in preparation of 3′‐O‐p‐monomethoxy‐ tritylthymidine. J. Org. Chem. 32:2365‐2366.
   Ogilvie, K.K., Thompson, E.A., Quilliam, M.A., and Westmore, J.B. 1974. Selective protection of hydroxyl groups in deoxynucleosides using alkylsilyl reagents. Tetrahedron Lett. 33:2865‐2868.
   Ogilvie, K.K., Usman, N., Nicoghosian, K., and Cedergren, R.J. 1988. Total chemical synthesis of a 77‐nucleotide‐long RNA sequence having methionine‐acceptance. Proc. Natl. Acad. Sci. U.S.A. 85:5764‐5768.
   Ohtsuka, E. and Iwai, S. 1987. Chemical synthesis of RNA. In Synthesis and Application of DNA and RNA (S.A. Narang, ed.) pp. 115‐136. Academic Press, Orlando, Fla.
   Ohtsuka, E., Taniyama, Y., Iwai, S., Yoshida, T., and Ikehara, M. 1984. Deoxyribonucleic acids and related compounds. VIII. Solid‐phase synthesis of deoxyribooligonucleotides with 3′‐modification by elongation in the 3′‐direction. Chem. Pharm. Bull. 32:85‐93.
   Oikawa, Y., Yoshioka, T., and Yonemitsu, O. 1982. Specific removal of o‐methoxybenzyl protection by DDQ oxidation. Tetrahedron Lett. 23:885‐888.
   Ozaki, H., Nakamura, A., Arai, M., Ogawa, Y., and Sawai, H. 1994. Synthesis and property of oligodeoxyribonucleotide bearing 5‐aminoalkyl‐2′‐deoxyuridine derivatives. Nucl. Acids Res. Symp. Ser. 31:49‐50.
   Ozaki, S., Yamashita, K., Konishi, T., Maekawa, T., Eshima, M., Uemura, A., and Ling, L. 1995. Enzyme aided regioselective acylation of nucleosides. Nucleosides Nucleotides 14:401‐404.
   Palom, Y., Alazzouzi, E., Gordillo, F., Grandas, A., and Pedroso, E. 1993. An acid‐labile linker for solid‐phase oligoribonucleotide synthesis using Fmoc group for 5′‐hydroxyl protection. Tetrahedron Lett. 34:2195‐2198.
   Patel, T.P., Millican, T.A., Bose, C.C., Titmas, R.C., Mock, G.A., and Eaton, M.A.W. 1982. Improvements to solid phase phosphotriester synthesis of deoxyoligonucleotides. Nucl. Acids Res. 18:5605‐5620.
   Patil, S.V., Mane, R.B., and Salunkhe, M.M. 1994. A facile method for detritylation of 5′‐O‐dimethoxy‐trityl‐3′‐O‐tert‐butyldimethylsilyl‐2′‐ deoxynucleosides. Synth. Commun. 24:2423‐2428.
   Paul, C.H. and Royappa, A.T. 1996. Acid binding and detritylation during oligonucleotide synthesis. Nucl. Acids Res. 24:3048‐3052.
   Pease, A.C., Solas, D., Sullivan, E.J., Cronin, M.T., Holmes, C.P., and Fodor, S.P.A. 1994. Light‐generated oligonucleotide arrays for rapid DNA sequence analysis. Proc. Natl. Acad. Sci. U.S.A. 91:5022‐5026.
   Pfleiderer, W., Stengele, K.P., Bergmann, F., Resmini, M., and Henke, C. 1995. How to synthesize a tRNA?. Nucleosides Nucleotides 14:843‐846.
   Pieken, W. 1997. Product anchored sequential synthesis: A novel process for the preparation of oligonucleotides. Abstracts, International Symposium on Nucleic Acids and Related Macromolecules, Ulm, Germany.
   Pirrung, M.C. and Bradley, J.‐C. 1995a. Dimethoxybenzoin carbonates: Photochemically removable alcohol protecting groups suitable for phosphoramidite‐based DNA synthesis. J. Org. Chem. 60:1116‐1117.
   Pirrung, M.C. and Bradley, J.‐C. 1995b. Comparison of methods for photochemical phosphoramidite‐based DNA synthesis. J. Org. Chem. 60:6270‐6276.
   Pirrung, M.C. and Lee, Y.R. 1993. Photochemically removable silyl protecting groups. J. Org. Chem. 58:6961‐6963.
   Pirrung, M.C., Fallon, L., and McGall, G. 1998. Proofing of photolithographic DNA synthesis with 3′,5′‐dimethoxybenzoinyloxycarbonyl‐protected deoxynucleoside phosphoramidites. J. Org. Chem. 63:241‐246.
   Prasad, A.K. and Wengel, J. 1996. Enzyme‐mediated protecting group chemistry on the hydroxyl groups of nucleosides. Nucleosides Nucleotides 15:1347‐1359.
   Ramage, R. and Wahl, F.O. 1993. 4‐(17‐Tetrabenzo[a,c,g,i]fluorenylmethyl)‐4′,4′′‐dimethoxy‐ trityl chloride: A hydrophobic 5′‐protecting group for the separation of synthetic oligonucleotides. Tetrahedron Lett. 34:7133‐7136.
   Reddy, M.P., Rampal, J.B., and Beaucage, S.L. 1987. An efficient procedure for the solid phase tritylation of nucleosides and nucleotides. Tetrahedron Lett. 28:23‐26.
   Reese, C.B. 1978. The chemical synthesis of oligo‐ and polynucleotides by the phosphotriester approach. Tetrahedron 34:3143‐3179.
   Reese, C.B. 1985. Some aspects of the chemical synthesis of oligoribonucleotides. Nucleosides Nucleotides 4:117‐127.
   Reese, C.B. 1989. The chemical synthesis of oligo‐ and polyribonucleotides. In Nucleic Acids and Molecular Biology, Vol. 3 (F. Eckstein and D.M.J. Lilley, eds.) pp. 164‐181. Springer‐Verlag, Berlin.
   Reese, C.B. and Skone, P.A. 1984. The protection of thymine and guanine residues in oligodeoxyribonucleotide synthesis. Chem. Soc. Perkin Trans. 1. 1263‐1271.
   Reese, C.B. and Stewart, J.C.M. 1968. Methoxyacetyl as a protecting group in ribonucleoside chemistry. Tetrahedron Lett. 40:4273‐4276.
   Reese, C.B. and Thompson, E.A. 1988. A new synthesis of 1‐arylpiperidin‐4‐ols. J. Chem. Soc. Perkin Trans. 1. 2881‐2885.
   Reese, C.B., Serafinowska, H., and Zappia, G. 1986. An acetal group suitable for the protection of 2′‐hydroxy functions in rapid oligoribonucleotide synthesis. Tetrahedron Lett. 27:2291‐2294.
   Regel, W., Stengele, E., and Seliger, H. 1974. Kinetik der Schutzgruppenabspaltung an Nucleosiden mittels 1H‐NMR‐Spektroskopie. Chem. Ber. 107:611‐615.
   Reiner, T. and Pfleiderer, W. 1987. β‐Substituted ethylsulfonyl chlorides as 5′‐OH protecting groups in nucleoside and nucleotide chemistry. Nucl. Acids Res. Symp. Ser. 18:161‐164.
   Riva, S., Chopineau, J., Kieboom, A.P.G., and Klibanov, A.M. 1988. Protease‐catalyzed regioselective esterification of sugars and related compounds in anhydrous dimethylformamide. J. Am. Chem. Soc. 110:584‐589.
   Robins, M.J., Samano, V., and Johnson, M.D. 1990. Periodinane oxidation, selective primary deprotection, and remarkably stereoselective reduction of tert‐butyldimethylsilyl‐protected ribonucleosides. Synthesis of 9‐(β‐D‐xylofuranosyl)adenine or 3′‐deuterioadenosine from adenosine. J. Org. Chem. 55:410‐412.
   Rosenthal, A., Cech, D., Veiko, V.P., Orezkaja, T.S., Kuprijanova, E.A., and Shabarova, Z.A. 1983. Triester‐Festphasensynthese von Oligodesoxyribonucleotiden an Polystyren‐Teflon Trägern. Tetrahedron Lett. 24:1691‐1694.
   Rosowsky, A., Solan, V.C., Sodroski, J.G., and Ruprecht, R.M. 1989. Synthesis of the 2‐chloro analogues of 3′‐deoxyadenosine, 2′,3′‐dideoxyadenosine, and 2′,3′‐didehydro‐2′,3′‐dideoxyadenosine as potential antiviral agents. J. Med. Chem. 32:1135‐1140.
   Sachdev, H.S. and Starkovsky, N.A. 1969. Enzymatic removal of acyl protecting groups. The use of dihydrocinnamoyl group in oligonucleotide synthesis and its cleavage by α‐chymotrypsin. Tetrahedron Lett. 9:733‐736.
   Sandström, A., Kwiatkowski, M., and Chattopadhyaya, J. 1985. Chemical synthesis of a pentaribonucleoside tetraphosphate constituting the 3′‐acceptor stem sequence of E. coli tRNAIle using 2′‐O‐(3‐methoxy‐1,5‐dicarbomethoxypentan‐3‐ yl)‐ribonucleoside building blocks. Application of a new achiral and acid‐labile 2′‐hydroxyl protecting group in tRNA synthesis. Acta Chem. Scand. B 39:273‐290.
   Scalfi‐Happ, C., Happ, E., and Chládek, S. 1987. New approach to the synthesis of 2′(3′)‐O‐aminoacyl‐oligoribonucleotides related to the 3′‐terminus of aminoacyl transfer ribonucleic acid. Nucleosides Nucleotides 6:345‐348.
   Schaller, H., Weimann, G., Lerch, B., and Khorana, H.G. 1963. Studies on polynucleotides. XXIV. The stepwise synthesis of specific deoxyribopolynucleotides (4). Protected derivatives of deoxyribonucleosides and new syntheses of deoxyribonucleoside‐3′‐phosphates. J. Am. Chem. Soc. 85:3821‐3827.
   Schirmeister, H., Himmelsbach, F., and Pfleiderer, W. 1993. The 2‐(4‐nitrophenyl)ethoxycarbonyl (npeoc) and 2‐(2,4‐dinitrophenyl)ethoxycarbonyl (dnpeoc) groups for protection of hydroxy functions in ribonucleosides and 2′‐deoxyribonucleosides. Helv. Chim. Acta 76:385‐401.
   Schmidt, G., Schlenk, R., and Seliger, H. 1988. The 4‐decyloxytrityl group as an aid in the affinity chromatography of synthetic oligonucleotides. Nucleosides Nucleotides 7:795‐799.
   Sekine, M. 1993. Selective and rapid O‐acylation of hydroxyl groups of nucleosides by means of phase transfer catalysis. Nat. Prod. Lett. 1:251‐256.
   Sekine, M. 1994. A new method for removal of modified trityl and pixyl groups by use of an acid species generated by reaction of diethyl oxomalonate with methanol. Nucleosides Nucleotides 13:1397‐1414.
   Sekine, M. and Hata, T. 1983. 4,4′,4′′‐Tris(benzoyloxy)trityl as a new type of base‐labile group for protection of primary hydroxyl groups. J. Org. Chem. 48:3011‐3014.
   Sekine, M. and Hata, T. 1984. 4,4′,4′′‐Tris(4,5‐dichlorophthalimido)trityl: A new type of hydrazine‐labile group as a protecting group of primary alcohols. J. Am. Chem. Soc. 106:5763‐5764.
   Sekine, M. and Hata, T. 1985. 4,4′,4′′‐Tris(levulinoyloxy)trityl as a new type of primary hydroxyl protecting group. Bull. Chem. Soc. Jpn. 58:336‐339.
   Sekine, M. and Hata, T. 1986. Synthesis of short oligoribonucleotides bearing a 3′‐ or 5′‐terminal phosphate by use of 4,4′,4′′‐tris(4,5‐dichlorophthalimido)trityl as a new 5′‐hydroxyl protecting group. J. Am. Chem. Soc. 108:4581‐4586.
   Sekine, M. and Hata, T. 1987. 3‐(Imidazol‐1‐yl‐methyl)‐4′,4′′‐dimethoxytrityl: A new functionalized 5′‐hydroxyl protecting group capable of rapid internucleotidic bond formation in the phosphorothio ester approach. J. Org. Chem. 52:946‐948.
   Sekine, M., Mori, T., and Wada, T. 1993. New 5′‐hydroxyl protecting groups for rapid internucleotide bond formation. Tetrahedron Lett. 34:8289‐8292.
   Seliger, H. 1972. Chlorameisensäureester von Nucleosiden—neue Zwischenprodukte für Synthesen mit Nucleinsäurebausteinen. Tetrahedron Lett. 39:4043‐4046.
   Seliger, H. 1993. Scale‐up of oligonucleotide synthesis. Solution phase. In Methods in Molecular Biology, Vol. 20: Protocols for Oligonucleotides and Analogs (S. Agrawal, ed.) pp. 391‐435. Humana Press, Totowa, N.J.
   Seliger, H. and Görtz, H.‐H. 1981. Specific separation of products in supported oligonucleotide syntheses using the triester method. Angew. Chem. Int. Ed. Engl. 20:683‐684.
   Seliger, H. and Kotschi, U. 1985. The p‐phenylazophenyloxycarbonyl protecting group: Selective deblocking and oligonucleotide synthesis avoiding acid steps. Nucleosides Nucleotides 4:153‐155.
   Seliger, H. and Schmidt, G. 1987. Derivatization with the 4‐decyloxytrityl group as an aid in the affinity chromatography of oligo‐ and polynucleotides. J. Chromatogr. 397:141‐151.
   Seliger, H., Holupirek, M., and Görtz, H.‐H. 1977a. Oligonucleotide support synthesis with affinity‐chromatographic separation of the product. Abstracts, XXVIth IUPAC International Congress of Pure and Applied Chemistry Tokyo. Abstract 265.
   Seliger, H., Holupirek, M., and Bach, T.C. 1977b. The lipoyl affinity group and its use in oligonucleotide synthesis. Commun. (Posters), Brit. Chem. Soc. Nucl. Group, 10th anniversary meeting, British Chem. Soc., Birmingham, U.K.
   Seliger, H., Holupirek, M., and Görtz, H.‐H. 1978. Solid‐phase oligonucleotide synthesis with affinity‐chromatographic separation of the product. Tetrahedron Lett. 24:2115‐2118.
   Seliger, H., Klein, S., Narang, C.K., Seemann‐Preising, B., Eiband, J., and Hauel, N. 1982. Solid‐phase synthesis of oligonucleotides using the phosphite method. In Chemical and Enzymatic Synthesis of Gene Fragments: A Laboratory Manual (H.G. Gassen and A. Lang eds.) pp. 81‐96. Verlag Chemie, Weinheim, Germany.
   Seliger, H., Zeh, D., Azuru, G., and Chattopadhyaya, J.B. 1983. Two new and efficient routes to the preparation of oligoribonucleotides of defined sequence. Chem. Scripta 22:95‐101.
   Seliger, H., Gupta, K.C., Kotschi, U., Spaney, T., and Zeh, D. 1986. New preparative methods in oligonucleotide chemistry and their application to gene synthesis. I. Improvements in the chemistry of solid‐phase oligonucleotide synthesis. Chem. Scr. 26:561‐567.
   Seliger, H., Schmidt, G., and Berner, S. 1987. Substituents with long alkyl chains as tools for the purification and immobilization of nucleic acids and their constituents. Biol. Chem. Hoppe‐Seyler 368:773‐774.
   Septak, M. 1996. Kinetic studies on depurination and detritylation of CPG‐bound intermediates during oligonucleotide synthesis. Nucl. Acids Res. 24:3053‐3058.
   Shabarova, Z.A. 1980. The application of solid phase method‐synthesized oligodeoxyribonucleotides to molecular biology problems. Nucl. Acids Res. Symp. Ser. 7:259‐279.
   Shimidzu, T. and Letsinger, R.L. 1968. Synthesis of deoxyguanylyldeoxyguanosine on an insoluble polymer support. J. Org. Chem. 33:708‐711.
   Singh, H.K., Cote, G.L., and Sikorski, R.S. 1993. Enzymatic regioselective deacylation of 2′,3′,5′‐tri‐O‐acylribonucleosides: Enzymatic synthesis of 2′,3′‐di‐O‐acylribonucleosides. Tetrahedron Lett. 34:5201‐5204.
   Singh, H.K., Cote, G.L., and Hadfield, T.M. 1994. Manipulation of enzyme regioselectivity by solvent engineering: Enzymatic synthesis of 5′‐O‐acylribonucleosides. Tetrahedron Lett. 35:1353‐1356.
   Sinha, N.D., Biernat, J., McManus, J., and Köster, H. 1984. Polymer support oligonucleotide synthesis. XVII. Use of β‐cyanoethyl‐N,N‐dialkylamino/N‐morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product. Nucl. Acids Res. 12:4539‐4557.
   Smith, M., Rammler, D.H., Goldberg, I.H., and Khorana, H.G. 1962. Studies on polynucleotides. XIV. Specific synthesis of the C3′‐C5′ interribonucleotide linkage. Syntheses of uridylyl‐(3′→5′)‐uridine and uridylyl‐(3′→5′)‐adenosine. J. Am. Chem. Soc. 84:430‐440.
   Sonveaux, E. 1986. The organic chemistry underlying DNA synthesis. Bioorg. Chem. 14:271‐325.
   Sproat, B.S. and Gait, M.J. 1984. Solid‐phase synthesis of oligodeoxyribonucleotides by the phosphotriester method. In Oligonucleotide Synthesis: A Practical Approach (M.J. Gait, ed.) pp. 83‐115. IRL Press, Oxford.
   Takaku, H., Morita, K., and Sumiuchi, T. 1983. Selective removal of terminal dimethoxytrityl groups. Chem. Lett. 1661‐1664.
   Tanaka, T. and Oishi, T. 1985. Chemical synthesis of deoxyribonucleotides containing deoxyadenosine at the 3′‐end on a polystyrene polymer support. Chem. Pharm. Bull. 33:5178‐5183.
   Tanimura, H. and Imada, T. 1990. Practical chemical synthesis of RNA fragments. Improvements in the preparation of ribonucleoside phosphoramidite units. Chem. Lett. 1715‐1718.
   Tanimura, H., Fukazawa, T., Sekine, M., Hata, T., Efcavitch, J.W., and Zon, G. 1988. The practical synthesis of RNA fragments in the solid phase approach. Tetrahedron Lett. 29:577‐578.
   Tanimura, H., Maeda, M., Fukazawa, T., Sekine, M., and Hata, T. 1989. Chemical synthesis of the 24 RNA fragments corresponding to hop stunt viroid. Nucl. Acids Res. 17:8135‐8147.
   Taunton‐Rigby, A. 1973. Oligonucleotide synthesis. III. Enzymatically removable acyl protecting groups. J. Org. Chem. 38:977‐985.
   Taunton‐Rigby, A., Kim, Y.‐H., Crosscup, C.J., and Starkovsky, N.A. 1972. Oligonucleotide synthesis. II. The use of substituted trityl groups. J. Org. Chem. 37:956‐964.
   Temsamani, J., Kubert, M., and Agrawal, S. 1995. Sequence identity of the n‐1 product of a synthetic oligonucleotide. Nucl. Acids Res. 23:1841‐1844.
   Ti, G.S., Gaffney, B.L., and Jones, R.A. 1982. Transient protection: Efficient one‐flask syntheses of protected deoxynucleosides. J. Am. Chem. Soc. 104:1316‐1319.
   Tong, G., Lawlor, J.M., Tregear, G., and Haralambidis, J. 1993. The synthesis of oligonucleotide‐polyamide conjugate molecules suitable as PCR primers. J. Org. Chem. 58:2223‐2231.
   Uemura, A., Nozaki, K., Yamashita, J., and Yasumoto, M. 1989a. Lipase‐catalyzed regioselective acylation of sugar moieties of nucleosides. Tetrahedron Lett. 30:3817‐3818.
   Uemura, A., Nozaki, K., Yamashita, J., and Yasumoto, M. 1989b. Regioselective deprotection of 3′,5′‐O‐acylated pyrimidine nucleosides by lipase and esterase. Tetrahedron Lett. 30:3819‐3820.
   Usman, N., Ogilvie, K.K., Jiang, M.‐Y., and Cedergren, R.J. 1987. Automated chemical synthesis of long oligoribonucleotides using 2′‐O‐silylated ribonucleoside 3′‐O‐phosphoramidites on a controlled‐pore glass support: Synthesis of a 43‐nucleotide sequence similar to the 3′‐half molecule of an Escheria coli formylmethionine tRNA. J. Am. Chem. Soc. 109:7845‐7854.
   van Boom, J.H. and Burgers, P.M.J. 1976. Use of levulinic acid in the protection of oligonucleotides via the modified phosphotriester method; synthesis of decaribonucleotide U‐A‐U‐A‐U‐A‐U‐A‐U‐A. Tetrahedron Lett. 52:4875‐4878.
   van Boom, J.H. and Wreesmann, C.T.J. 1984. Chemical synthesis of small oligoribonucleotides in solution. In Oligonucleotide Synthesis: A Practical Approach (M.J. Gait, eds.) pp. 153‐183. IRL Press, Oxford.
   Wada, T., Mochizuki, A., Sato, Y., and Sekine, M. 1998a. Functionalisation of solid supports with N‐unprotected deoxyribonucleotides. Tetrahedron Lett. 39:5593‐5596.
   Wada, T., Naotake, K., Mori, T., and Sekine, M. 1998b. Stereocontrolled synthesis of dithymidine phosphorothioates by use of a functionalized 5′‐protecting group bearing an imidazole residue. Nucleosides Nucleotides 17:351‐364.
   Waldmann, H. and Sebastian, D. 1994. Enzymatic protecting group techniques. Chem. Rev. 94:911‐937.
   Waldmeier, F., de Bernardini, S., Leach, C.A., and Tamm, C. 1982. 246. Nucleosides and Nucleotides. Part 19. On detritylation with zinc bromide in oligonucleotide synthesis. Helv. Chim. Acta 65:2472‐2475.
   Wallraff, G., Labadie, J., Brock, P., Di Pietro, R., Nguyen, T., Huynh, T., Hinsberg, W., and McGall, G. 1997. DNA sequencing on a chip. CHEMTECH. 22‐32.
   Weiler, J. and Pfleiderer, W. 1995. An improved method for large scale synthesis of oligonucleotides applying the NPE/NPEOC‐strategy. Nucleosides Nucleotides 14:917‐920.
   Weiss, R., Birch‐Hirschfeld, E., and Witkowski, W. 1984. Comparative study of the synthesis of oligodeoxynucleotides achieved by the phosphotriester method on various supports. Nucl. Acids Res. Symp. Ser. 14:313‐314.
   Welch, C.J., Zhou, X.‐X., and Chattopadhyaya, J. 1986. Synthesis of an mRNA fragment of alanyl‐tRNA synthetase gene in Escherichia coli using the 6‐methyl‐3‐pyridyl group for protection of the imide functions of uridine and guanosine. Acta Chem. Scand. B 40:817‐825.
   Winnacker, E.‐L. and Dörper, T. 1982. Solid‐phase synthesis of oligonucleotides using the phosphoramidite method. In Chemical and Enzymatic Synthesis of Gene Fragments: A Laboratory Manual (H.G. Gassen and A. Lang eds.) pp. 97‐102. Verlag Chemie, Weinheim, Germany.
   Wong, C.‐H., Chen, S.‐T., Hennen, W.J., Bibbs, J.A., Wang, Y.‐F., Liu, J.L.‐C., Pantoliano, M.W., Whitlow, M., and Bryan, P.N. 1990. Enzymes in organic synthesis: Use of subtilisin and a highly stable mutant derived from multiple site‐specific mutations. J. Am. Chem. Soc. 112:945‐953.
   Yamakage, S., Sakatsume, O., Furuyama, E., and Takaku, H. 1989. 1‐(2‐Chloroethoxy)ethyl group for the protection of 2′‐hydroxyl group in the synthesis of oligoribonucleotides. Tetrahedron Lett. 30:6361‐6364.
   Yu, D., Tang, J., Iyer, R.P., and Agrawal, S. 1994. Diethoxy‐N,N‐diisopropyl phosphoramidite as an improved capping reagent in the synthesis of oligonucleotides using phosphoramidite chemistry. Tetrahedron Lett. 35:8565‐8568.
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