'One-pot' preparation of N-(Carbonylamino)amino acids and half- acid/half-ester urea dipeptides directly from α-amino acids

Tetrahedron Letters

Volumn 40, Issue 15, 1999, Pages 2895-2898

  Weiberth, Franz J ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID DERIVATIVE; CARBONYL DERIVATIVE;

AMINO ACID ANALYSIS; AMINO ACID SYNTHESIS; ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; DRUG SYNTHESIS;

EID: 0033537802     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00388-3     Document Type: Article

References (33)

1. Zhang, X.; Rodrigues, J.; Evans, L.; Hinkle, B.; Ballantyne, L.; Peña, M. J. Org. Chem. 1997, 62, 6420-6423.
2. Yamada, Y. et al. Chem. Pharm. Bull. 1997, 45, 1631-1641.
3. See, for example, (a) von Geldern, T. W. et al. J. Med. Chem. 1996, 39, 957-967.
4. (b) Fukami, T. et al. J. Med. Chem. 1996, 39, 2313-2330, and references cited therein.
5. (c) He, J. X.; Cody, W. L.; Doherty, A. M. J. Org. Chem. 1995, 60, 8262-8266.
6. Palmer, J. T.; Rasnick, D.; Klaus, J. L.; Brömme, D. J. Med. Chem. 1995, 38, 3193-3196.
7. Batey, R. A.; Santhakumar, V.; Yoshina-Ishii, C.; Taylor, S. D. Tetrahedron Lett. 1998, 39, 6267-6270.
8. Majer, P.; Randad, R. S. J. Org. Chem. 1994, 59, 1937-1938.
9. Nowick, J. S.; Powell, N. A.; Nguyen, T. M.; Noronha, G. J. Org. Chem. 1992, 57, 7364-7366.
10. (a) A method for preparing N-(carbonylamino)amino acids by reaction of N,O-bis(trimethylsilyl)amino acids with isocyanates is suitable for the synthesis of N,N'-disubstituted ureas, but it is not applicable for preparing the trisubstituted ureas reported here. See: Arrieta, A.; Palomo, C. Synthesis 1982, 1050-1052. Similarly, N,N'-disubstituted ureas can also be prepared from reaction of amino acids with trichloroacetamides. See: Atanassova, I. A.; Petrov, J. S.; Balabanova, A. N.; Mollov, N. M. Synth. Commun.1989, 19, 2947-2954.
11. (a) A method for preparing N-(carbonylamino)amino acids by reaction of N,O-bis(trimethylsilyl)amino acids with isocyanates is suitable for the synthesis of N,N'-disubstituted ureas, but it is not applicable for preparing the trisubstituted ureas reported here. See: Arrieta, A.; Palomo, C. Synthesis 1982, 1050-1052. Similarly, N,N'-disubstituted ureas can also be prepared from reaction of amino acids with trichloroacetamides. See: Atanassova, I. A.; Petrov, J. S.; Balabanova, A. N.; Mollov, N. M. Synth. Commun. 1989, 19, 2947-2954.
12. (b) A solid phase, combinatorial approach to preparing half-acid/half-ester urea dipeptides has been described: Nieuwenhuijzem, J. W.; Conti, P. G. M.; Ottenheijm, H. C. J.; Linders, J. T. M. Tetrahedron Lett. 1998, 39, 7811-7814.
13. Hils, J.; Rühlmann, K. Chem. Ber., 1967, 100, 1638-1345.
14. (a) Kricheldorf, H. R. Synthesis 1970, 592-593.
15. (b) Kricheldorf, H. R. Liebings Ann. Chem. 1972, 763, 17-38.
16. (a) Gmeiner, P. G.; Feldman, P. L.; Chu-Moyer, M. Y.; Rapoport, H. J. Org. Chem. 1990, 55, 3068-3074.
17. (b) Jamison, T. F.; Rapoport, H. Org. Synth. 1992, 71, 226-235.
18. (a) Barlos, K.; Papaioannou, D.; Theodoropoulos, D. J. Org. Chem. 1982, 47, 1324-1326.
19. (b) Hipskind, P. A. et al. J. Org. Chem. 1995, 60, 7033-7036.
20. (a) Kricheldorf, H. R.; Schultze, J. Synthesis 1976, 739-741.
21. (b) Chung, J. Y. L.; Zhao, D.; Hughes, D. L.; Grabowski, E. J. J. Tetrahedron 1993, 49, 5767-5776.
22. The sequence is considered "one-pot" in the sense that no intermediates are isolated.
23. Eckert, H.; Forster, B. Angew. Chem. Int. Ed. Engl. 1987, 26, 894-895.
24. -1 was observed. It appears from this preliminary experiment that the silyl group participates in the formation of isocyanate 3. Additional in situ FT IR studies probing this reaction are on-going, and will be reported in due time.
25. O-Silyl protected α-isocyanato acids 3 have been prepared from amino acids via N-(aryloxycarbonyl)amino acids. See: Kricheldorf, H. R. Synthesis 1970, 649-651.
26. In limited experience, isolated yields were generally lower and more variable for compounds 7 than for compounds 5.
27. 2, 90:10:1 EtOAc/MeOH/HOAc, ninhydrin.
28. Sample preparation: injected 5 μL of solution prepared from ca. 0.5 mg of compound dissolved in 1 mL of the mobile phase; column: 4.6 mm × 25 cm Chirobiotic T (Teicoplanin); mobile phase: 70:30 EtOH (USP)/20 mM ammonium citrate dibasic (pH 4.0); flow: 1 mL/min; detection: uv at 210 nm; retention times: 5a, 3.75 min, 5b, 3.15 min. Compounds were enantiomerically homogeneous within the detection limits of the method.
29. Nowick, J. S.; Holmes, D. L.; Noronha, G.; Smith, E. M.; Nguyen, T. M.; Hauling, S.-L. J. Org. Chem. 1996, 61, 3929-3934.
30. 1H NMR spectroscopy.
31. Techniques such as using finely divided amino acid and vigorous agitation were employed in the heterogeneous silylations. Also, to prevent loss of TMSCl, joints were carefully sealed and an efficient condenser was used.
32. 22 = -27.6° (c = 1.00, MeOH) for enantiomer 5b obtained from L-Leu (1b).
33. If necessary, nuisance emulsions at the interfaces can be broken by using Celite® and filtering through a 40-μ fritted filter.