Rapid cleavage of cyclic tertiary amides of Kemp's triacid: Effects of ring structure

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 16, 2004, Pages 4153-4156

  Dougan, Michael L ^a,b   Chin, Jonathan L ^a,c   Solt, Ken ^a,d   Hansen, David E ^a  

^a AMHERST COLLEGE   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Amide cleavage; Kemp's triacid

Indexed keywords

ACID; AMIDE; BENZENE DERIVATIVE; PIPERIDONE DERIVATIVE; PROLINE DERIVATIVE;

ALLYLATION; ARTICLE; CONCENTRATION RESPONSE; CYCLIZATION; DEGRADATION; DERIVATIZATION; LYSIS; MATHEMATICAL COMPUTING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULAR MECHANICS; REACTION ANALYSIS;

ACIDS; AMIDES; KINETICS; MOLECULAR STRUCTURE;

EID: 3142754095     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.06.024     Document Type: Article

References (13)

1. Menger F.M., Ladika M. J. Am. Chem. Soc. 110:1988;6794-6796
2. Kemp D.S., Petrakis K.S. J. Org. Chem. 46:1981;5140-5143
3. Radzicka A., Wolfenden R. J. Am. Chem. Soc. 118:1996;6105-6109
4. Smith R.M., Hansen D.E. J. Am. Chem. Soc. 120:1998;8910-8913
5. Menger F.M., Ladika M. J. Org. Chem. 55:1990;3006-3007
6. Curran T.P., Borysenko C.W., Abelleira S.M., Messier R.J. J. Org. Chem. 59:1994;3522-3529
7. Johnson F. Chem. Rev. 68:1968;375-413
8. + 308.1862. Found 308.1859
9. + 428.2073. Found 428.2067
10. 1H NMR spectrum was recorded to ensure that the anhydride (and in the case of prolyl derivative 11, the benzyl ester) had completely hydrolyzed. An aliquot of DCl solution was then added (from between 7 and 20 μL depending on the final pD for the pyrrolidyl and piperidyl amide derivatives, or from between 33 and 40 μL for prolyl amide derivative). The NMR tube was rapidly inverted many times to mix the solution
11. ® pH strips were used to measure the pD of each solution. The pD was taken as the 'pH' indicated plus 0.5, the correction factor for borate buffer (Schowen, K. B.; Schowen, R. L. Methods Enzymol. 1982, 87, 551-606)
12. 2-, and/or -N-CH- for the prolyl derivative, signals were used to determine the extent of reaction. Rate constants were then calculated using the integrated first-order rate equation
13. Molecular mechanics calculations were performed using HyperChem™ RELEASE 5.11 Pro for Windows (Hypercube, Inc.). The MM + force field with the block-diagonal Newton-Raphson algorithm was employed