A new and efficient solid phase synthesis of hydroxamic acids

Journal of Organic Chemistry

Volumn 62, Issue 21, 1997, Pages 7088-7089

  Ngu, Khehyong ^a   Patel, Dinesh V ^a  

^a Versicor Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZYLAMINE DERIVATIVE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DRUG CARRIER; HYDROXAMIC ACID; MATRIX METALLOPROTEINASE INHIBITOR; METALLOPROTEINASE INHIBITOR; STROMELYSIN; TETRAHYDROPYRAN DERIVATIVE; THERMOLYSIN; TRIFLUOROACETIC ACID;

ACYLATION; AQUEOUS SOLUTION; ARTICLE; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; SOLID STATE;

EID: 0030732272     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo971274g     Document Type: Article

References (30)

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15. a = 10) of such hydroxamate intermediates is vulnerable to side reactions such as alkylations and cyclizations under basic and Mitsunobu type conditions, thus limiting the potential for further synthetic manipulations typically required for synthesizing nonpeptidic metalloenzyme inhibitors. For SPS of O-linked hydroxamic acids, see (a) Floyd, C. D.; Lewis, C. N.; Patel, S. R.; Whittaker, M. Tetrahedron Lett. 1996, 37, 8045. (b) Richter, L. S.; Desai, M. C. Tetrahedron Lett. 1997, 38, 321. (c) Gordeev, M. F.; Hui, H. C.; Gordon, E. M.; Patel, D. V. Tetrahedron Lett. 1997, 38, 1729. (d) Miller, S. L.; McGuire, C.; Chan, W. C. Tetrahedron Lett. 1997, 38, 3311.
16. a = 10) of such hydroxamate intermediates is vulnerable to side reactions such as alkylations and cyclizations under basic and Mitsunobu type conditions, thus limiting the potential for further synthetic manipulations typically required for synthesizing nonpeptidic metalloenzyme inhibitors. For SPS of O-linked hydroxamic acids, see (a) Floyd, C. D.; Lewis, C. N.; Patel, S. R.; Whittaker, M. Tetrahedron Lett. 1996, 37, 8045. (b) Richter, L. S.; Desai, M. C. Tetrahedron Lett. 1997, 38, 321. (c) Gordeev, M. F.; Hui, H. C.; Gordon, E. M.; Patel, D. V. Tetrahedron Lett. 1997, 38, 1729. (d) Miller, S. L.; McGuire, C.; Chan, W. C. Tetrahedron Lett. 1997, 38, 3311.
17. a = 10) of such hydroxamate intermediates is vulnerable to side reactions such as alkylations and cyclizations under basic and Mitsunobu type conditions, thus limiting the potential for further synthetic manipulations typically required for synthesizing nonpeptidic metalloenzyme inhibitors. For SPS of O-linked hydroxamic acids, see (a) Floyd, C. D.; Lewis, C. N.; Patel, S. R.; Whittaker, M. Tetrahedron Lett. 1996, 37, 8045. (b) Richter, L. S.; Desai, M. C. Tetrahedron Lett. 1997, 38, 321. (c) Gordeev, M. F.; Hui, H. C.; Gordon, E. M.; Patel, D. V. Tetrahedron Lett. 1997, 38, 1729. (d) Miller, S. L.; McGuire, C.; Chan, W. C. Tetrahedron Lett. 1997, 38, 3311.
18. a = 10) of such hydroxamate intermediates is vulnerable to side reactions such as alkylations and cyclizations under basic and Mitsunobu type conditions, thus limiting the potential for further synthetic manipulations typically required for synthesizing nonpeptidic metalloenzyme inhibitors. For SPS of O-linked hydroxamic acids, see (a) Floyd, C. D.; Lewis, C. N.; Patel, S. R.; Whittaker, M. Tetrahedron Lett. 1996, 37, 8045. (b) Richter, L. S.; Desai, M. C. Tetrahedron Lett. 1997, 38, 321. (c) Gordeev, M. F.; Hui, H. C.; Gordon, E. M.; Patel, D. V. Tetrahedron Lett. 1997, 38, 1729. (d) Miller, S. L.; McGuire, C.; Chan, W. C. Tetrahedron Lett. 1997, 38, 3311.
19. Ngu, K.; Patel, D. V. Tetrahedron Lett. 1997, 38, 973.
20. Attempted cleavage of the product from the Wang resin gave the p-hydroxybenzyl-derived adduct derived from partial O-cleavage of the linker group.
21. Aldehyde 5 was purchased from Perseptive Biosystems Inc., MA. For synthesis and early applications of HAL linker, see Albericio, F.; Kneib-Cordonier, N.; Biancalana, S.; Gera, L.; Maseda, I.; Hudson, D.; Barany, G. J. Org. Chem. 1990, 55, 3730.
22. Direct attachment of linker 5 to resin followed by oxime formation with alkoxyamines 6 and 7 and reduction on solid support to arrive at alkoxyamines 13 and 12, respectively, was attempted but found to be less satisfactory compared to the current approach.
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30. Further applications of Tsunda's various modified Mitsunobu reagent systems for solid phase N-alkylation of sulfonamides are in progress and will be reported separately in the near future.