Regioselective nitration of Nα,N1-bis(trifluoroacetyl)-l-tryptophan methyl ester: Efficient synthesis of 2-nitro and 6-nitro-N-trifluoroacetyl-l-tryptophan methyl ester

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 21, 2008, Pages 5750-5752

  Osborne, Andrew S ^a   Som, Phanneth ^a   Metcalf, Jessica L ^a   Phillips, Robert S ^a,b  

^a UNIVERSITY OF GEORGIA   (United States)

^b University of Georgia   (United States)

Author keywords

Indole; Nitration; Nitrotryptophan; Tryptophan

Indexed keywords

2 NITRO N TRIFLUOROACETYLTRYPTOPHAN METHYL ESTER; 6 NITRO N TRIFLUOROACETYLTRYPTOPHAN METHYL ESTER; ACETIC ACID DERIVATIVE; ESTER DERIVATIVE; FLUORINE DERIVATIVE; N ALPHA,N 1 BIS(TRIFLUOROACETYL)TRYPTOPHAN METHYL ESTER; NITRO DERIVATIVE; TRYPTOPHAN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; NITRATION; QUANTUM YIELD; REACTION ANALYSIS; REACTION TIME; STEREOCHEMISTRY; SYNTHESIS;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; MAGNETIC RESONANCE SPECTROSCOPY; NITRATES; TRYPTOPHAN;

EID: 53949083509     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.086     Document Type: Article

References (20)

1. Bittner S., Scherzer R., and Harlev E. Amino Acids 33 (2006) 19
2. Munn D.H., Zhou M., Attwood J.T., Bondarev I., Conway S.J., Marshall B., Brown C., and Mellor A.L. Science 281 (1998) 1191
3. Mellor A.L., and Munn D.H. Immunol.Today 20 (1999) 469
4. Lee M.S., and Phillips R.S. Bioorg. Med. Chem. Lett. 1 (1991) 477
5. Dua R.K., and Phillips R.S. Tetrahedron Lett. 33 (1992) 29
6. Ma C., Liu X., Li X., Flippen-Anderson J., Yu S., and Cook J.M. J. Org. Chem. 66 (2001) 4525
7. Sloan M.J., and Phillips R.S. Bioorg. Med. Chem. Lett. 2 (1992) 1053
8. Lee M., and Phillips R.S. Bioorg. Med. Chem. Lett. 2 (1992) 1563
9. Welch M., and Phillips R.S. Bioorg. Med. Chem. Lett. 9 (1999) 637
10. Phillips R.S. Tetrahedron: Asymmetry 15 (2004) 2787
11. Miles E.W., and Phillips R.S. Biochemistry 24 (1985) 4694
12. De Fazi R., Berti G., and Da Settimo A. Gazz. Chim. Ital. 89 (1959) 2238
13. Moriya T., Hagio K., and Yoneda N. Bull. Chem. Soc. Jpn. 48 (1975) 2217
14. Phillips R.S., and Cohen L.A. J. Heterocycl. Chem. 25 (1988) 191
15. Phillips R.S., and Cohen L.A. Tetrahedron Lett. 24 (1983) 5555
16. Phillips R.S., and Cohen L.A. J. Am. Chem. Soc. 108 (1986) 2023
17. Makisumi S., and Saroff H.A. J. Gas Chromatogr. 1 (1965) 23
18. Pelkey E.T., and Gribble G.W. Synthesis (1999) 1117
19. Jiang J., and Gribble G.W. Tetrahedron Lett. 43 (2002) 4115
20. 1-bis(trifluoroacetyl)-l-tryptophan methyl ester (2.0 g, 4.84 mmol) was placed in a 50 ml round bottomed flask with 10 ml of solvent, either acetic anhydride or trifluoroacetic acid. The reaction mixture was cooled to -2 °C in an ice-salt bath. A solution of 70% nitric acid (3 ml) in the same solvent (10 ml) was added drop-wise and the reaction was stirred. After 45 min, the reaction was quenched by pouring into ice-cold 5% aqueous sodium carbonate solution. Additional sodium bicarbonate was added until the pH of the mixture was 7.5. The resulting yellow precipitate was collected by filtration, and the cake was washed with cold water. The dried product was dissolved in a minimal volume of ethyl acetate and crystallized by addition of hexane. After standing at 4 °C overnight, the product was collected by filtration, washed with a small volume of hexanes and air-dried.