o-Nitrobenzyl as a photocleavable nitrogen protecting group for indoles, benzimidazole, and 6-chlorouracil

Tetrahedron Letters

Volumn 39, Issue 5-6, 1998, Pages 359-362

  Voelker, Troy ^a   Ewell, Tim ^a   Joo, Jean ^a   Edstrom, Eric D ^a  

^a UNIVERSITY OF MONTANA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 CHLOROURACIL; BENZIMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; UNCLASSIFIED DRUG; URACIL DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; METHODOLOGY; PHOTOLYSIS; REACTION ANALYSIS; REACTION TIME;

EID: 0032576869     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10600-1     Document Type: Article

References (22)

1. 1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, J. Wiley, New York, 1991.
2. 2. a) Muchowski, J. M.; Solas, D. R. J. Org. Chem. 1984, 49, 203.
3. b) Anderson, H. J.; Groves, J. K. Tetrahedron Lett. 1971, 3165.
4. c) Katritzky, A. R.; Khan, G. R.; Marson, C. M. J. Heterocydic Chem. 1987, 24, 641.
5. d) Gonzalez, C.; Greenhouse, R.; Tallabs, R.; Muchowski, J. M. Can J. Chem. 1983, 61, 1697.
6. 3. Removal of N-benzyl groups from indoles and imidazoles typically requires strong basic, acidic, or reducing reaction conditions, a) (MeLi, rt, >12 h) Suzuki, H.; Tsukuda, A.; Kondo, M.; Aizawa, M.; Senon, Y.; Nakajima, M.; Watanabe, T.; Yokoyama, Y.; Murakami, Y. Tetrahedron Lett. 1995, 31, 1671.
7. 3, PhH) Murakami, Y.; Watanabe, T.; Kobayashi, A.; Yokoyama, Y. Synthesis 1984, 738.
8. 2O, 3 d) Evans, D. A.; Lundy, K. M. J. Am. Chem. Soc. 1992, 114, 1495.
9. 4. A 2,4-dimethoxybenzyl group was first used to protect the amide side-chain of glutamine and asparagine residues and can be readily cleaved using TFA or aqueous HF. Pietta, P. G.; Cavallo, P.; Marshall. G. R. J. Org. Chem. 1971, 36, 3966.
10. 5. a) Edstrom, E. D.; Wei, Y. J. Org. Chem. 1993, 58, 403.
11. b) Edstrom, E. D.; Wei, Y. J. Org. Chem. 1994, 59, 6902.
12. 6. Specifically, the need arose for an alkyl-based pyrrole protecting group which is stable to acid and basic reaction conditions and can be removed selectively in the presence of acid or base deavable protecting groups elsewhere in the molecule.
13. 7. For previous use of the ONB group of amino and carboxyl function of amino acids, see: a) Patchomik, A.; Amit, B.; Woodward, R. B. J. Am. Chem. Soc. 1970, 92, 6333.
14. b) Barltrop, J. A.; Plant, P. J.; Schofield, P. Tetrahedron Lett. 1966, 822.
15. For a review on photoremovable protecting groups, see: c) Pilla Rajasekharen, V. N. Synthesis 1980, 1.
16. 8. a) Kalbag, S. M.; Roeske, R. W. J. Am. Chem. Soc. 1975, 97, 440.
17. b) Acedo, M.; De Clercq, E.; Eritja, R. J. Org. Chem. 1995, 60, 6262.
18. 9. The use of NaH was less desirable due to competing deprotonation of the ONB-Br which lead to dark colored by-products. This problem was avoided by the use of less basic LiH. Excess (10 eq) of this hydride was used in order to shorten the reaction times which were monitored by TLC.
19. 3) δ 161.9, 140.9, 136.7, 135.4, 129.1, 128.8, 128.1, 124.9, 122.2, 121.1, 120.4, 110.3, 106.2, 103.4, 78.0 (CHOH).
20. 11. For example, ONB protected 3-indolylacetonitrile and 2-pyridinone afforded less than satisfactory deprotection yields (<50%).
21. 12. For a related problem involving the secondary reaction of the liberated amino group from ONB protected amino acid derivatives with the aldehyde group of this by-product, see: ref 7a.
22. 13. We give thanks to a referee for suggesting this explanation.