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. 1990 Jan 11;18(1):41–49. doi: 10.1093/nar/18.1.41

New synthetic routes to protected purine 2'-O-methylriboside-3'-O-phosphoramidites using a novel alkylation procedure.

B S Sproat 1, B Beijer 1, A Iribarren 1
PMCID: PMC330201  PMID: 2308835

Abstract

A highly selective alkylation procedure has been developed enabling new synthetic routes to be established for protected purine 2'-O-methylriboside-3'-O-phosphoramidites; building blocks for the assembly of 2'-O-methyloligoribonucleotides. The new procedure avoids the use of the highly toxic and potentially explosive reagent diazomethane and is far superior to the use of silver oxide/methyl iodide. Moreover, the use of highly versatile key intermediates will enable the synthesis of a wide variety of base modified analogues as well as other 2'-O-alkylriboside derivatives.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BROOM A. D., ROBINS R. K. THE DIRECT PREPARATION OF 2'-O-METHYLADENOSINE FROM ADENOSINE. J Am Chem Soc. 1965 Mar 5;87:1145–1146. doi: 10.1021/ja01083a045. [DOI] [PubMed] [Google Scholar]
  2. Coddington A. Some substrates and inhibitors of adenosine deaminase. Biochim Biophys Acta. 1965 Jun 22;99(3):442–451. doi: 10.1016/s0926-6593(65)80198-9. [DOI] [PubMed] [Google Scholar]
  3. Furukawa Y., Kobayashi K., Kanai Y., Honjo M. Synthesis of 2'-O-methyluridine, 2'-O-methylcytidine and their relating compounds. Chem Pharm Bull (Tokyo) 1965 Nov;13(11):1273–1278. doi: 10.1248/cpb.13.1273. [DOI] [PubMed] [Google Scholar]
  4. Gin J. B., Dekker C. A. The preparation and properties of O-methylated adenosine derivatives. Biochemistry. 1968 Apr;7(4):1413–1420. doi: 10.1021/bi00844a025. [DOI] [PubMed] [Google Scholar]
  5. Inoue H., Hayase Y., Asaka M., Imura A., Iwai S., Miura K., Ohtsuka E. Synthesis and properties of novel nucleic acid probes. Nucleic Acids Symp Ser. 1985;(16):165–168. [PubMed] [Google Scholar]
  6. Inoue H., Hayase Y., Imura A., Iwai S., Miura K., Ohtsuka E. Synthesis and hybridization studies on two complementary nona(2'-O-methyl)ribonucleotides. Nucleic Acids Res. 1987 Aug 11;15(15):6131–6148. doi: 10.1093/nar/15.15.6131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Inoue H., Hayase Y., Iwai S., Ohtsuka E. Sequence-dependent hydrolysis of RNA using modified oligonucleotide splints and RNase H. FEBS Lett. 1987 May 11;215(2):327–330. doi: 10.1016/0014-5793(87)80171-0. [DOI] [PubMed] [Google Scholar]
  8. Inoue H., Hayase Y., Iwai S., Ohtsuka E. Sequence-specific cleavage of RNA using chimeric DNA splints and RNase H. Nucleic Acids Symp Ser. 1988;(19):135–138. [PubMed] [Google Scholar]
  9. Khwaja T. A., Robins R. K. Purine nucleosides. XVI. Synthesis of the naturally occurring 2 -O-methylpurine ribonucleosides and related derivatives. J Am Chem Soc. 1966 Aug 5;88(15):3640–3643. doi: 10.1021/ja00967a031. [DOI] [PubMed] [Google Scholar]
  10. Lamond A. I., Sproat B., Ryder U., Hamm J. Probing the structure and function of U2 snRNP with antisense oligonucleotides made of 2'-OMe RNA. Cell. 1989 Jul 28;58(2):383–390. doi: 10.1016/0092-8674(89)90852-0. [DOI] [PubMed] [Google Scholar]
  11. Mukai S., Shibahara S., Morisawa H. A new method for the unidirectional deletion of DNA with Bal 31 nuclease using 2'-O-MeRNA-DNA chimeric adaptors. Nucleic Acids Symp Ser. 1988;(19):117–120. [PubMed] [Google Scholar]
  12. Nyilas A., Chattopadhyaya J. Synthesis of O2'-methyluridine, O2'-methylcytidine, N4,O2'-dimethylcytidine and N4,N4,O2'-trimethylcytidine from a common intermediate. Acta Chem Scand B. 1986 Nov;40(10):826–830. doi: 10.3891/acta.chem.scand.40b-0826. [DOI] [PubMed] [Google Scholar]
  13. Robins M. J., Naik S. R., Lee A. S. Nucleic acid related compounds. 12. The facile and high-yield stannous chloride catalyzed monomethylation of the cis-glycol system of nucleosides by diazomethane. J Org Chem. 1974 Jun 28;39(13):1891–1899. doi: 10.1021/jo00927a022. [DOI] [PubMed] [Google Scholar]
  14. Robins M. J., Naik S. R. Nucleic acid related compounds. 1. Methylation and transformation of 4-methoxy-2-pyrimidinone 1- -D-ribofuranoside into 2'-O-methyl nucleoside components of ribonucleic acid, their analogs, and derivatives. Biochemistry. 1971 Sep 14;10(19):3591–3597. doi: 10.1021/bi00795a017. [DOI] [PubMed] [Google Scholar]
  15. Schulhof J. C., Molko D., Teoule R. The final deprotection step in oligonucleotide synthesis is reduced to a mild and rapid ammonia treatment by using labile base-protecting groups. Nucleic Acids Res. 1987 Jan 26;15(2):397–416. doi: 10.1093/nar/15.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shibahara S., Mukai S., Nishihara T., Inoue H., Ohtsuka E., Morisawa H. Site-directed cleavage of RNA. Nucleic Acids Res. 1987 Jun 11;15(11):4403–4415. doi: 10.1093/nar/15.11.4403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sinha N. D., Biernat J., McManus J., Köster H. Polymer support oligonucleotide synthesis XVIII: use of beta-cyanoethyl-N,N-dialkylamino-/N-morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product. Nucleic Acids Res. 1984 Jun 11;12(11):4539–4557. doi: 10.1093/nar/12.11.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sproat B. S., Lamond A. I., Beijer B., Neuner P., Ryder U. Highly efficient chemical synthesis of 2'-O-methyloligoribonucleotides and tetrabiotinylated derivatives; novel probes that are resistant to degradation by RNA or DNA specific nucleases. Nucleic Acids Res. 1989 May 11;17(9):3373–3386. doi: 10.1093/nar/17.9.3373. [DOI] [PMC free article] [PubMed] [Google Scholar]

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