4,4′-Dimethoxytrityl and 4,4′,4″-trimethoxytrityl as protecting groups for amino functions; selectivity for primary amino groups and application in ¹⁵N-labelling

Abstract

4,4′-Dimethoxytrityl tetrafluoroborate (DMT⁺ BF₄^–) and 4,4′,4″-trimethoxytrityl tetrafluoroborate (TMT⁺ BF₄^–) are useful reagents for protecting primary and some secondary amines. Protected amines are obtained either by reaction of DMT⁺ BF₄^– or TMT⁺ BF₄^– with the amine or by alkylating DMT- or TMT-amine (available from DMT⁺ BF₄^– and TMT⁺ BF₄^– by treatment with ammonia). Alkylation of DMT- or TMT-amine stops after monoalkylation. Deprotection of the alkylated DMT- and TMT-amine is achieved by treatment with an acid of appropriate molarity (e.g. 0.1 M HCl in 1∶1 tetrahydrofuran–water for TMT-amines). The value of the methodology described is illustrated by a synthesis of (¹⁵NH₂) adenosine. X-Ray molecular structures of one DMT and two TMT derivatives are reported.

References

1. C. Bleasdale, S. B. Ellwood and B. T. Golding, J. Chem. Soc., Perkin Trans. 1, 1990, 803.
2. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 1992.
3. F. Balkenhohl, C. von dem Bussche-Hünnefeld, A. Lansky and C. Zechel, Angew. Chem., Int. Ed. Engl., 1996, 35, 2289.
4. H. Waldmann and A. Reidel, Angew. Chem., Int. Ed. Engl., 1997, 36, 647.
5. L. Agarwal, A. Yamazaki, P. J. Cashion and H. G. Khorana, Angew. Chem., Int. Ed. Engl., 1972, 11, 451.
6. C. A. Bunton and S. K. Huang, J. Am. Chem. Soc., 1974, 96, 515.
7. M. Ashwell, C. Bleasdale, B. T. Golding and I. K. O'Neill, J. Chem. Soc., Chem. Commun., 1990, 955.
8. C. Morin and M. Vidal, Tetrahedron, 1992, 48, 9277.
9. V. F. Patel, J. N. Hardin, J. J. Starling and J. M. Mastro, Bioorg. Med. Chem. Lett., 1995, 5, 507.
10. V. F. Patel, J. N. Hardin, G. B. Grindey and R. M. Shultz, Bioorg. Med. Chem. Lett, 1995, 5, 513.
11. L. Zervas and D. M. Theodoropoulos, J. Am. Chem. Soc., 1956, 78, 1359.
12. P. Mamos, G. Karigiaanis, C. Anthanassopoulos, S. Bitcha, D. Kalpaxis and D. Papaioannou, Tetrahedron Lett., 1995, 36, 5187.
13. C. C. Leznoff and T. M. Fyles, J. Chem. Soc., Chem. Commun., 1976, 251.
14. C. C. Leznoff, T. M. Fyles and J. Weatherston, Can. J. Chem., 1977, 55, 1143.
15. T. M. Fyles, C. C. Leznoff and J. Weatherston, Can. J. Chem., 1978, 56, 1031.
16. C. C. Leznoff and T. W. Hall, Tetrahedron Lett., 1982, 23, 3023.
17. K. Barlos, D. Gatos, I. Kallitsis, D. Papaioannou and P. Sotiriou, Liebigs Ann. Chem., 1988, 1079.
18. K. Barlos, D. Gatos, J. Kallitsis, G. Papaphotiu, P. Sotiriou, Y. Wenqing and W. Schäfer, Tetrahedron Lett., 1989, 30, 3943.
19. C. Chen, L. A. Ahlberg Randall, R. B. Miller, A. D. Jones and M. J. Kurth, J. Am. Chem. Soc., 1994, 116, 2661.
20. The Combinatorial Chemistry Catalog, Calbiochem-Novabiochem (UK) Ltd., Nottingham, Feb. 1997.
21. C. Bleasdale, B. T. Golding, W. H. Lee, H. Maskill, J. Riseborough and E. Smits, J. Chem. Soc., Chem. Commun., 1994, 93.
22. M. Canle, J. Crugeiras, I. Demertas and H. Maskill, Org. Reactivity (Tartu), 1997, submitted for publication.
23. F. H. Allen and O. Kennard, Chem. Design Automation News, 1993, 8, 31.
24. B. T. Golding, P. K. Slaich, G. Kennedy, C. Bleasdale and W. P. Watson, Chem. Res. Toxicol., 1996, 9, 147.
25. X. Gao and R. A. Jones, J. Am. Chem. Soc., 1987, 109, 1275.
26. G. M. Sheldrick, SHELXTL Manual, Version 5, Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA, 1995.