[59128-90-4]  · C7H6N4O2S  · 1-Phenylsulfonyl-1H-tetrazole  · (MW 210.24)

(coupling reagent for oligonucleotide solution synthesis using the phosphotriester method1-4)

Physical Data: mp 86-92 °C.

Solubility: insol H2O; sol pyridine, CH2Cl2; reacts slowly with H2O and protic solvents.

Form Supplied in: white crystals; not available from commercial sources.

Analysis of Reagent Purity: prior to use, the purity should be determined by mp.

Preparative Method: by reaction of Benzenesulfonyl Chloride (1 equiv) and tetrazole (1 equiv) in the presence of Triethylamine (1 equiv) in dioxane at 5 °C for 2 h. A crystalline product was obtained after dissolving the crude material in benzene, shaking with silica gel, filtering, and evaporating in vacuo to dryness.

Handling, Storage, and Precautions: the dry solid should be stored in a desiccator with drierite at 4 °C. The material decomposes completely after 20 days at 25 °C, and it should be used immediately following preparation. Cation: Avoid contact with metals and metal salts, since tetrazole may form explosive metal salts. Contact with strong oxidizers or strong heat may cause fire or explosion.

1-Phenylsulfonyl-1H-tetrazole (1) has been used as a condensing reagent in deoxyoligonucleotide solution synthesis by the phosphotriester method.1-3 It activates 5-dimethoxytrityl (DMT) deoxynucleoside 3-(p-chorophenyl) phosphates in anhydrous pyridine, allowing the coupling reaction with 5-hydroxy nucleoside in 30 min at 25 °C, yielding the corresponding p-chlorophenyl phosphate dimer in 74% yield. This reaction has been extended for the preparation of oligodeoxynucleotides containing up to 12 bases with coupling times in the range of 30-120 min at 25 °C (eq 1). Couplings mediated by (1) occur more rapidly than with the corresponding 2,4,6-trimethyl and 2,4,6-triisopropyl analogs and no sulfonation at the 5-hydroxy group has been observed.1,3

Furthermore, (1) has been used in anhydrous pyridine for 24 h at 25 °C for the preparation of a ribonucleotide dimer in 60% yield (eq 2).

Although (1) has not been used in solid-phase oligonucleotide synthesis, another more stable arylsulfonyl derivative, 1-(mesitylsulfonyl)-3-nitro-1,2,4-triazole (MSNT),5,6 is commonly used in that strategy by the phosphotriester approach.7

1. Stawinski, J.; Hozumi, T.; Narang, S. A. CJC 1976, 54, 670.
2. Stawinski, J.; Hozumi, T.; Narang, S. A.; Bahl, C. P.; Wu, R. Nucleic Acids Res. 1977, 4, 353.
3. Narang, S. A.; Stawinski, J. U.S. Patent 4 059 592 1977 (CA 1978, 88, 191 349v).
4. Ogilvie, K. K.; Pon, R. T. Nucleic Acids Res. 1980, 8, 2105.
5. Reese, C. B.; Abasawa, A. TL 1980, 21, 2265.
6. Tan, Z. K.; Ikuta, S.; Huang, T.; Dugaiczyk, A.; Itakura, K. Cold Spring Harbor Symp. Quant. Biol. 1982, 47, 383 (CA 1983, 99, 22 773a).
7. Itakura, K.; Rossi, J. J.; Wallace, R. B. Annu. Rev. Biochem. 1984, 53, 323.

Ramon Eritja

CID-CSIC, Barcelona, Spain

Steven A. Kates & Fernando Albericio

Millipore Corporation, Bedford, MA, USA

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