New hydroxylamines for the synthesis of hydroxamic acids

Tetrahedron Letters

Volumn 39, Issue 43, 1998, Pages 7865-7868

  Barlaam, Bernard ^a   Hamon, Annie ^a   Maudet, Mickaël ^a  

^a ZI La Pompelle   (France)

Author keywords

Hydroxamic acids; Hydroxylamines; Protecting groups

Indexed keywords

HYDROXAMIC ACID DERIVATIVE; HYDROXYLAMINE; MATRIX METALLOPROTEINASE INHIBITOR;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; DRUG SYNTHESIS;

EID: 0032558622     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01760-2     Document Type: Article

References (22)

1. 1. a) Beckett, R.P.; Davidson, A.H.; Drummond, A.H.; Huxley, P.; Whittaker, M. Drug Discovery Today 1996, 1, 16
2. b) Beckett, R.P., Whittaker, M. Exp. Opin. Ther. Patents 1998, 8, 259
3. c) Hagmann, W.K.; Lak, M.W.; Becker, J.W. in Ann. Rep. Med. Chem, Bristol, J.A. (Ed) Academic Press Inc 1996, Vol. 31, 231
4. 3/anisole): Nagata, W.; Nishitani, Y.; Aoki, T.; Yoshida, T. J. Antibiotics, 1988, 316
5. b) p-methoxybenzyl "Solid Phase analog": Richter, S.L.; Desai, M.C. Tetrahedron Lett. 1997, 38, 321
6. c) p-methoxybenzyl "Solid Phase analog": Floyd, C.; Lewis, C.; Patel, S.R.; Whittaker, M. Tetrahedron Lett. 1996, 37, 8045
7. d) MacPherson, L.J. et al. J. Med. Chem, 1997, 40, 2525
8. e) Trityl "Solid Phase analog": Bauer, U.; Ho, W.B.; Koskinen, A.M.P. Tetrahedron Lett. 1997, 38, 7233
9. f) 2-Chlorotrityl "Solid Phase analog": Mellor, S.L.; McGuire, C.; Chan, W.C. Tetrahedron Lett. 1997, 38, 3311
10. 3. Mention of 2,4-dimethoxybenzyl for hydroxamate protection in Ciba Geigy US Patent, US5506242 (1996)
11. 4. Lee, B.H; Miller, M.J. J. Org. Chem. 1983, 48, 24
12. 5. Isolation of TNFα convertase: a) Black, R.A. and al. Nature 1997, 385, 729
13. b) Moos, M.L. and al. Nature 1997, 385, 733
14. 6. The acidic NH group (pKa about 10) of O-protected hydroxamates is vulnerable to side reactions like alkylation or acylation. For other N,O-bisprotection of hydroxamates: a) N,O-benzyl: Bashiardes, G.; Bodwell, G.J.; Davies, S.G. J. Chem. Soc. Perkin Trans. 1 1993, 459
15. b) N-BOC-O-TBDMS or N-BOC-O-THP: Altenburger, J.M.; Mioskowski, C.; d'Orchymont, H.; Schirlin, D.; Schalk, C.; Tarnus, C. Tetrahedron Lett. 1992, 33, 5055
16. c) During that work, an independant communication disclosed the N-2,4,6-dimethoxybenzyl-O-THP or -O-allyl protection on solid phase: Gu, K.N.; Patel, D.V. J. Org. Chem. 1997, 62, 7088
17. 3 calc. C 59.00, H 7.15, N 7.65 found C 58.10, H 7.10. N 7.35.
18. 8. Grochowski, E.; Jurczak, J. Synthesis, 1976, 682
19. 3): 3.78-3.81 (m, 15 H), 4.14 (s, 2H), 4.75 (s, 2H), 6.10 (s, 2H), 6.45 (m, 2H), 7.27 (m, 1H); m.p.: 72-74 °C.
20. 10. When treated with 1% TFA-dichloromethane for 15 mn, the fully N,O-protected hydroxamate 6b gave the corresponding N-protected-O-deprotected hydroxamate (not isolated, characterised by HPLC/MS) with only traces of the fully deprotected hydroxamic acid 6.
21. (12) Evaporation of the filtrate gave 6 which can be further purified by trituration in ether (10 mg; 65 %).
22. 3COOH: C: 69.48, H: 6.87). (equation presented)