Rapid generation of cis-constrained norstatine analogs using a TMSN3-modified Passerini MCC/N-capping strategy

Tetrahedron Letters

Volumn 43, Issue 38, 2002, Pages 6833-6835

  Nixey, Thomas ^a   Hulme, Christopher ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DERIVATIVE; ASPARTIC PROTEINASE INHIBITOR; CYANIDE; DICHLOROMETHANE; ISOCYANIDE; N BUTYLOXYCARBONYL ALPHA AMINOALDEHYDE; NORSTATINE DERIVATIVE; PROTEINASE; TRIMETHYLSILYL DERIVATIVE; TRIMETHYLSILYLAZIDE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS; PASSERINI REACTION; REACTION ANALYSIS;

EID: 0037119735     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(02)01505-8     Document Type: Article

References (24)

1. (a) Dunn, B. M. Structure and Function of the Aspartic Proteases: Genetics, Structures, and Mechanisms; Plenum Press: New York, 1991; Vol. 306, xviii, 585 pp.
2. (b) Takahashi K. Aspartic Proteinases: Structure, Function, Biology, and Biomedical Implications. 1995;Plenum Press, New York.
3. Lee C.E., Kick E.K., Ellman J.A. J. Am. Chem. Soc. 120:1998;9735-9747. and references cited therein.
4. (a) Spatola A.F. Weinstein B., Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins. 7:1983;267 Dekker, New York.
5. (b) West M.L., Fairlie D.P. Trends Pharmacol. Sci. 16:1995;67.
6. (c) Huff J.R. J. Med. Chem. 34:1991;2305.
7. (a) Zabrocki J., Smith G.D., Dunbar J.B., Iijima H., Marshall G.R. J. Am. Chem. Soc. 110:1988;5875-5880.
8. (b) Yu K.-L., Johnson R.L. J. Org. Chem. 52:1987;2051-2059.
9. (c) Marshall, G. R.; Humblet. C.; Van Opdenbosch, N.; Zabrocki, J. In Peptides: Synthesis-Structure-Function; Proceedings of the Seventh American Peptide Symposium; Rich, D. H.; Gross, E., Eds.; Pierce Chemical: Rockford, IL, 1981; pp. 669-672.
10. (a) May B.C.H., Abell A.D. Tetrahedron Lett. 42:2001;5641-5644.
11. (b) Abell A.D., Foulds G.J. J. Chem. Soc., Perkin Trans. 1. 17:1997;2475-2482.
12. (a) Passerini M. Gazz. Chim. Ital. 51:1921;126.
13. (b) Passerini M. Gazz. Chim. Ital. 51:1921;181.
14. (a) Salvino J., Kumar V.N., Orton E., Airey J., Kiesow T., Crawford K., Rose M., Krolikowski P., Drew M., Engers D., Krolinkowski D., Herpin T., Gardyan M., McGeehan G., Labaudiniere R. J. Comb. Chem. 2:2000;691-697.
15. (b) Drew M., Orton E., Krolikowski P., Salvino J., Kumar N.V. J. Comb. Chem. 2:2000;8-9.
16. (c) Jones, W.; Overland, D.; Poppe, L.; Cardenas, J.; Pate, M.; Hulme, C. LabAutomation2002, T002.
17. 3 has also been employed in the Ugi reaction: (i) Bienayme, H. Tetrahedron Lett. 1998, 39, 2735; (ii) Nixey, T.; Kelly, M.; Hulme, C. Tetrahedron Lett. 2000, 41, 8729; (iii) Nixey, T.; Kelly, M.; Semin, D.; Hulme, C. Tetrahedron Lett. 2002, 43, 3681.
18. 3 has also been employed in the Ugi reaction: (i) Bienayme, H. Tetrahedron Lett. 1998, 39, 2735; (ii) Nixey, T.; Kelly, M.; Hulme, C. Tetrahedron Lett. 2000, 41, 8729; (iii) Nixey, T.; Kelly, M.; Semin, D.; Hulme, C. Tetrahedron Lett. 2002, 43, 3681.
19. 3 has also been employed in the Ugi reaction: (i) Bienayme, H. Tetrahedron Lett. 1998, 39, 2735; (ii) Nixey, T.; Kelly, M.; Hulme, C. Tetrahedron Lett. 2000, 41, 8729; (iii) Nixey, T.; Kelly, M.; Semin, D.; Hulme, C. Tetrahedron Lett. 2002, 43, 3681.
20. 3 has also been employed in the Ugi reaction: (i) Bienayme, H. Tetrahedron Lett. 1998, 39, 2735; (ii) Nixey, T.; Kelly, M.; Hulme, C. Tetrahedron Lett. 2000, 41, 8729; (iii) Nixey, T.; Kelly, M.; Semin, D.; Hulme, C. Tetrahedron Lett. 2002, 43, 3681.
21. +theoretical value 334.1874; actual value 334.1876. dM/M=0.60 ppm.
22. +theoretical value 389.1726; actual value 389.1735. dM/M=2.3 ppm.
23. Production of an 80-member array was successfully completed using a 96 well filter plate encapsulated in a reaction frame assembly. A slurry of TFP resins (20 μmol), DMF (350 μL) and the free amine (18 μmol) was heated at 60°C for 18 h, cooled, and the mixture was then filtered into a collection plate and the solvent was evaporated in vacuo at 65°C. Scavenging with PS-NCO (1 equiv., 24 h) was performed to remove any remaining free amine. The secondary alcohol present in the products showed little reactivity towards the polymer bound isocyanate under the reaction conditions.
24. 3CN to 100% over 15 min. The HPLC was interfaced with an APCI probe, and detection was performed at UV 215 nm.