Preparation of acid-labile resins with halide linkers and their utility in solid phase organic synthesis

Tetrahedron Letters

Volumn 38, Issue 6, 1997, Pages 973-976

  Ngu, Khehyong ^a   Patel, Dinesh V ^a  

^a Versicor Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RESIN;

ALKYLATION; ARTICLE; DRUG DESIGN; DRUG SYNTHESIS; IN VITRO STUDY; MATERIALS; METHODOLOGY; PEPTIDE SYNTHESIS;

EID: 0031562072     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02502-6     Document Type: Article

References (17)

1. 1 a) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385.
2. b) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555.
3. c) Gordon, E. M.; Gallop, M. A., Patel, D.Y. Acc. of Chem Res. 1996, 29, 144-154.
4. d) Patel D. V., Gordon, E. M. Drug Discovery Today 1996, 1, 134-144.
5. 2 a) Plunkett, M. J.; Ellman, J. A. J. Org. Chem. 1995, 60, 6006.
6. b) Backes, B. J.; Virgilio, A. A.; Ellman, J. A. J. Am. Chem. Soc. 1996, 118, 3055-3056.
7. 3 Simple chloromethyl polystyrene-divinylbenzene (Merrifield) resin or bromomethyl polyethyleneglycol polystyrene (Tentagel S Br) resin do not possess a cleavable linker and are therefore unsuitable. The 2-chlorotrityl resin is too labile and too bulky for practical utility in the current study.
8. 4 a) S.W.; Wang, J. Am. Chem. Soc. 1973, 95, 1328.
9. b) A. Florsheimer et al. "Peptides 1990, Proc. 21st European Peptide Symposium", E. Giralt & D. Andreu (Eds), ESCOM, Leiden, 1991, pp 131.
10. 5 Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part B. (1990, 3rd Edition), Chapter 3, Functional group interconversion by nucleophilic substitution, pp 121-128.
11. 1H NMR.
12. 2, but has limited stability and is probably getting partially hydrolyzed to the alcohol,
13. b) The tosyl and nosyl Wang resins (3, X = OTs or ONs) gave no desired sulfonamide product 5, indicating that most probably they are formed but are rather too stable and unreactive.
14. c) NA = not attempted. Based on the results obtained in 7b, the Tentagel S Ac tosyl and nosyl resins (4, X = OTs or ONs) were not included in the study.
15. 8 A sulfonamide group has recently been desribed as an anchoring group on solid support. Beaver, K. A.; Siegmund, A. C.; Spear, K. L. Tet. Lett. 1996, 37, 1145-1148.
16. 9 Tentagel S AC derived bromo resin 4 (R = OMe, X = Br) has also been found to be stable at 0 °C for 1 month, and further stability studies are currently in progress.
17. 10 Numerous applications of these halide resins (3 and 4, X = Br, I) for synthesis of non-peptidic, drug-like scaffold libraries are under investigation, and will be reported in the near future.