A novel linkage for the solid-phase synthesis of hydroxamic acid

Tetrahedron Letters

Volumn 38, Issue 41, 1997, Pages 7233-7236

  Bauer, Udo ^a,b   Ho, Wen Bin ^b   Koskinen, Ari M P ^a  

^a UNIVERSITY OF OULU   (Finland)

^b FIBROGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROXAMIC ACID;

ARTICLE; CATALYSIS; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030667268     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01678-X     Document Type: Article

References (11)

1. a) Neilands, J. B. Science 1967, 156, 3781.
2. b) Bauer, L. and Exner O. Angew. Chem. Int. Ed. Engl. 1974, 13, 376.
3. Beckett, R. P.; Davidson, A. H.; Drummond, A. H.; Huxley, P. and Whittaker, M. Drug Discovery Today 1996, 1, 16 and references cited therein.
4. During the course of this work methods for the synthesis of hydroxamic acids on solid support have been published: a) Floyd, C. D.; Lewis, C. N.; Patel, S. R. and Whittaker, M. Tetrahedron Lett. 1996, 37, 8045.
5. b) Richter, L. S.; Desai, M. C. Tetrahedron Lett. 1997, 38, 321.
6. c) Mellor, S.L.; McGuire, C.; Chan, W.C. Tetrahedron Lett. 1997, 38, 3311.
7. To a solution of N-hydroxyphthalimide (0.8 g, 5 mmol) and triethylamine (0.5 g, 5 mmol) in 8 mL dry DMF was added trityl chloride resin (1.0 g, 1 mmol/g loading, Novabiochem). After 12 h the resin was collected by filtration, washed successively with DMF, water, THF, MeOH and diethylether and then dried in vacuo. This resin was suspended in THF (10 mL) and hydrazine hydrat (1 mL) was added. After 12 h the resin was collected, washed with DMF, 5 M ammonium hydroxid solution, water, THF, MeOH and diethylether and then dried in vacuo. Loading >= 0.9 mmol/g. FT-IR (3: vmax (KBr) 1792, 1743, 1667, and 1602 cm-1; 4: vmax (KBr) 1653, and 1597 cm-1) revealed the absence of any carbonyl substituent confirming the hydrazinolysis of phthalimide. The loadings of 3 and 4 were determined by weight recovery of N-hydroxyphthalimide (upon cleavage) and phthalylhydrazide byproduct, respectively. They correlated well with the observed yields of products.
8. + + 1], 203 (29), 186 (78), 104 (96), 44 (100). Reactions of polymer bound materials were monitored by FT-IR. In addition, 15% by weight of each dry resin-bound intermediate was retained and the products resulted upon cleavage from the solid support were characterized by NMR and MS.
9. Knorr, R.; Trzeciak, A.; Bannwarth, W. and Gillessen, G. Tetrahedron Lett. 1989, 15, 1927.
10. Kolodziej, St. A. and Hamper B. C. Tetrahedron Lett. 1996, 37, 5277.
11. Zuckermann, R. N.; Kerr, J. M.; Kent, S. B. H. and Moos, W.H. J. Am. Chem. Soc. 1992, 114, 10646.