Automated RNA-synthesis with photocleavable sugar and nucleobase protecting groups

Synlett

Volumn , Issue SPEC. ISS., 1999, Pages 930-934

  Stutz, Alfred ^a   Pitsch, Stefan ^a  

^a Organ Chemisches Lab E   (Switzerland)

Author keywords

Aminoacylation; Base protecting groups; Phosphoramidites; Photolabile protection; RNA synthesis

Indexed keywords

ADENINE DERIVATIVE; CARBONYL DERIVATIVE; GUANINE DERIVATIVE; NUCLEOSIDE; RNA; SUGAR;

AMINOACYLATION; ARTICLE; CHIRALITY; NUCLEAR MAGNETIC RESONANCE; PHOTOLYSIS; RNA SEQUENCE; RNA SYNTHESIS;

EID: 0033047736     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1999-3098     Document Type: Article

References (22)

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2. Hayakawa, Y.; Kato, H.; Uchiyama, H. K.; Noyori, R. J. Org. Chem. 1986, 51, 2402. Hayakawa, Y.; Wakabayashi, S.; Kato, H.; Noyori, R. J. Am. Chem. Soc. 1990, 112, 1691. Hayakawa, Y.; Hirose, M.; Hayakawa, M.; Noyori, R. J. Org. Chem. 1995, 60, 925.
3. Hayakawa, Y.; Kato, H.; Uchiyama, H. K.; Noyori, R. J. Org. Chem. 1986, 51, 2402. Hayakawa, Y.; Wakabayashi, S.; Kato, H.; Noyori, R. J. Am. Chem. Soc. 1990, 112, 1691. Hayakawa, Y.; Hirose, M.; Hayakawa, M.; Noyori, R. J. Org. Chem. 1995, 60, 925.
4. Hayakawa, Y.; Kato, H.; Uchiyama, H. K.; Noyori, R. J. Org. Chem. 1986, 51, 2402. Hayakawa, Y.; Wakabayashi, S.; Kato, H.; Noyori, R. J. Am. Chem. Soc. 1990, 112, 1691. Hayakawa, Y.; Hirose, M.; Hayakawa, M.; Noyori, R. J. Org. Chem. 1995, 60, 925.
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10. The synthesis of longer conjugates is not reported.
11. The chemical synthesis of the truncated t-RNAs allows the incorporation of natural or unnatural modified nucleosides and would extend the scope of the method.
12. The preparation of a trimeric aminoacylated RNA-sequence from a partially protected RNA-precursor has been reported. Thereby, Fmoc ([(9-fluorenyl)methoxy]carbonyl), MTHP (4-methoxytetrahydropyran-4-yl), BPOC ([2-(4-biphenylyl)-2-propyloxy]carbonyl were employed as protecting groups for the nucleobases, the sugar-moieties and the amino acid, respectively. The tedious, stepwise deprotection procedure yielded only 20-30%: Hagen, M. D.; Scalfi-Happ, C.; Happ, E.; Chladek, S. J. J. Org. Chem. 1988, 53, 5040. Hagen, M. D.; Chladek, S. J. J. Org. Chem. 1989, 54, 3189.
13. The preparation of a trimeric aminoacylated RNA-sequence from a partially protected RNA-precursor has been reported. Thereby, Fmoc ([(9-fluorenyl)methoxy]carbonyl), MTHP (4-methoxytetrahydropyran-4-yl), BPOC ([2-(4-biphenylyl)-2-propyloxy]carbonyl were employed as protecting groups for the nucleobases, the sugar-moieties and the amino acid, respectively. The tedious, stepwise deprotection procedure yielded only 20-30%: Hagen, M. D.; Scalfi-Happ, C.; Happ, E.; Chladek, S. J. J. Org. Chem. 1988, 53, 5040. Hagen, M. D.; Chladek, S. J. J. Org. Chem. 1989, 54, 3189.
14. Wu, X.; Pitsch, S. Nucleic Acids Res. 1998, 26, 4315.
15. 2), 124.7, 129.3, 130.0, 134.5 (4 CH), 138.1, 147.5, 150.8 (3C).
16. 2 and chloride. The reagent is stable in biphasic reaction mixtures, where chloride ions are extracted into the aqueous phase (as realized in the preparation of 12 from 9).
17. 3) 1:1→9:1):1.00 g (75%) 15 as off-white, solid foam.
18. 3), seem to react by addition to the carbonyl group, followed by elimination of 2-nitrobenzyl alcohol.
19. The coinjections were carried out on a reversed-phase column (see Figure 1, 0 → 20% B (30 min) and on an ion-exchange column (Nucleogel SAX, 10 mM phosphate (pH 6) → 10 mM phosphate + 0.2 M KCI (30 min).
20. Obtained from XERAGON AG (Zürich, Switzerland)
21. Picles, U.; Zürcher, W.; Schär, M.; Moser, H. E. Nucleic Acids Res. 1993, 21, 3191.
22. Stutz, A.; Kuntze, S.; Pitsch, S. in preparation.