A solid phase synthesis of miconazole analogs via an iodoetherification reaction

Tetrahedron Letters

Volumn 37, Issue 32, 1996, Pages 5687-5690

  Tortolani, David R ^a   Biller, Scott A ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; IMIDAZOLE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0030570868     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01222-1     Document Type: Article

References (22)

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4. (b.) Kam, K.; Salmon, S.; Hersch, E.; Hruby, V.; Kaznierski, W.; Knaap, R. Nature 1991, 354, 82.
5. (c.) Houghton, R.; Pinilla, C.; Blondelle, S.; Apple, J.; Dooley, C.; Cuevero, J. Nature 1991, 354, 84.
6. (d.) Bunin, B.; Ellman, J. J. Am. Chem. Soc. 1992, 114, 10997.
7. (e.) Dewitt, S.; Kiely, J.; Stankovic, C.; Schroeder, M.; Cody, D.; Pavia, M. Proc. Natl. Acd. Sci. USA, 1993, 90, 6909.
8. (f.) Alper, J. Science 1994, 264, 1399.
9. 3. Godefroi, E.F.; Heeres, J.; van Cutsem, J.; Janssen, P. A. J. J. Med. Chem. 1969, 12, 784.
10. 4. (a.) Barrany, G.; and Merrifield, R.B. (1980) Peptides 2, 1.
11. (b.) Brodansky, M.; Klausner, Y.S.; Ondetti, M.A.; Peptide Synthesis, 2nd ed., Wiley, 1976.
12. (c.) Merrifield resin purchased from Advanced ChemTech, copolymer of chloromethylpolystyrene cross-linked with 1% divinyl benzene, 100-200 mesh, 1.2 mmol of Cl/g resin.
13. 2O (1:1, 5×10 mL), DME (5×10 mL), MeOH (5×10 mL) and then dried under high vacuum. A second treatment was performed to ensure high conversion.
14. 2O (1:1, 5×10 mL), DMF(3×1 mL), MeOH (5×10 mL) and then dried under high vacuum. A second treatment was performed to ensure high conversion.
15. 7. Other conditions attempted: a.) displacement of iodide 48 with imidazole in DMF at 75°C,
16. b.) displacement with imidazole in the presence of silver triflate in DMF at 75 °C and
17. c.) displacement with 1-(trimethylsilyl)imidazole in DMF at 75 °C.
18. +).
19. 9. UV detection at 215 nm.
20. 10. Samples were purified by preparative HPLC using a YMC S5 ODS column, 30 × 250 mm, eluted with a gradient from 20% to 100% aqueous methanol containing 0.1% TFA over 20 minutes. Appropriate fractions were collected based on UV absorbance at 215 nm and were concentrated in vacuo. System hardware included a Shimadzu SCL-10A system controller, 2-Shimadzu LC-8A solvent pumps, a Shimadzu SPD-10A detector (equipped with preparative flow cell), a Shimadzu SIL 10-A autosampler equipped for 2-ml injection and a Shimadzu FRC-10A fraction collector.
21. 11. Purified compound isolated as TFA salt.
22. +).