Solid-phase synthesis of cyclooctadepsipeptide PF1022A analogs using a cyclization-cleavage method with grime resin

Tetrahedron Letters

Volumn 38, Issue 5, 1997, Pages 757-760

  Lee, Byung H ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHELMINTIC AGENT; CYCLO(DEXTRO LACTYL N METHYLLEUCYL DEXTRO 3 PHENYLLACTYL N METHYLLEUCYL DEXTRO LACTYL N METHYLLEUCYL DEXTRO 3 PHENYLLACTYL N METHYLLEUCYL); CYCLODEPSIPEPTIDE; CYCLOPEPTIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REACTION ANALYSIS; TECHNIQUE;

EID: 0031016106     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02454-9     Document Type: Article

References (22)

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6. (c) Dutton, F. E.; Nelson, S. J. J. Antibiotics 1994, 47, 1322.
7. (a) Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233.
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11. (c) Sasaki, T.; Kaiser, E. T. J Org. Chem. 1991, 56, 3159.
12. (a) Ösapay, G.; Profit, A.; Taylor, J. W. Tetrahedron Lett. 1990, 31, 6121.
13. (b) Xu, M.; Nishino, N.; Mihara, H.; Fujimoto, T.; Izumiya, N. Chemistry Lett. 1992, 191.
14. (c) Kates, S. A.; Solé N. A.; Johnson, C. R.; Hudson, D.; Barany G.; Albercio, F. Tetrahedron Lett. 1993, 34, 1549.
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17. 6 + H requires 392.2073).
18. 9 + H requires 667.3594).
19. Compound l0a (2.15 g, 3.86 mmol), DMAP (610 mg, 5 mmol), and Kaiser oxime (Novabiochem, 0.91 mmol/g, 2 g, 1.82 mmol) were suspended in DCM (80 mL). The mixture was treated with DIG (0.94 mL, 5.4 mmol) and stirred for 16 h. The resin was washed with DCM (2 × 25 mL), MeOH (2 × 25 mL), DMF (2 × 25 mL), and DCM (2 × 25 mL). The washed resin was dried in vacuo for 4 h to give 4a (2.67 g, 0.65 mmol/g by cleavage reaction with morpholine).
20. Resin-bound peptide 4a (250 mg, 0.16 mmol) was suspended in TFA/DCM (25%, 4 mL). The mixture was stirred for l h at room temperature, washed with DCM (2 × 25 mL), MeOH (2 × 25 mL), DMF (2 × 25 mL), and DCM (2 × 25 mL). The washed resin was dried in vacuo for l h to give resin-bound peptide 4a having a free amino group. This resin was suspended in DMF (4 mL) and treated with Boc-L-MeLeu-D-Lac-OH (170 mg, 0.54 mmol), DIEA (0.2 mL), and PyBrop (Novabiochem, 250 mg, 0.54 mmol). The mixture was stirred at room temperature for 1.5 h. The resin was washed with DCM (2 × 25 mL), MeOH (2 × 25 mL), DMF (2 × 25 mL), and DCM (2 × 25 mL). The washed resin was dried in vacuo for 4 h to give resin-bound peptide 11a (257 mg).
21. t = 13.34 min (90% pure, RP 8 column; gradient: 50 to 90% acetonitrile/H2O + 0.1% TFA over 20 min).
22. 12 + Na requires 950.5044).