Asymmetric synthesis of RK-682 and its analogs, and evaluation of their protein phosphatase inhibitory activities

Tetrahedron Letters

Volumn 37, Issue 48, 1996, Pages 8775-8778

  Sodeoka, Mikiko ^a   Sampe, Ruriko ^a   Kagamizono, Terumi ^b   Osada, Hiroyuki ^b  

^a SAGAMI CHEMICAL RESEARCH CENTER   (Japan)

^b INST OF PHYS AND CHEMICAL RESEARCH   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; PHOSPHOPROTEIN PHOSPHATASE; RK 682; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG SYNTHESIS; FIBROBLAST; HUMAN; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030602210     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02029-1     Document Type: Article

References (17)

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11. 3), mp 245-260 °C, dec.) of (R)-1a by treatment of (A)-1a with either 1 equiv of sodium methoxide in methanol or 1/2 mol equiv of magnesium ethoxide in THF. The spectra of these salts were, again, inconsistent with that of natural sample of RK-682.
12. -1, Elemental Analysis C 59.77, H 8.96. Silicon derivatives of β-diketone have been reported, see: (a) Rochow, E. G. "Comprehensive Inorganic Chemistry", Ed. Trotman-Dickenson, A. F. Vol. 1, pp1465-1467 (1973).
13. 2Si or its oligomers are also possible. Although the exact structure of this silicon complex is unclear, the biologically active form of RK-682 in the aqueous assay buffer should be (R)-1a, the hydrolyzed product of this complex.
14. 9. The ability of a GST-VHR fusion protein to dephosphoryiate p-nitrophenylphosphate was measured in a buffer containing 25 mM MOPS, pH 6.5, 5 mM EDTA, and 1 mM DTT. For VHR phosphatase, see: Ishibashi, T.; Bottaro, D. P.; Chan, A.; Miki, T.; Aaronson, S. A. Proc. Natl Acad. Sci. USA 1992, 89, 12170-12174.
15. 2, 0.1 mM DTT, 0.1 mM PMSF, and 5% glycerol. For cdc25A, see: Hoffmann, I.; Draetta, G.; Karsenti, E. EMBO J. 1994, 13, 4302-4310. For cdc25B, see: Honda, R.; Ohba, Y. Nagata, A.; Okayama, H.; Yasuda, H. FEBS Lett. 1993, 318, 331-334.
16. 2, 0.1 mM DTT, 0.1 mM PMSF, and 5% glycerol. For cdc25A, see: Hoffmann, I.; Draetta, G.; Karsenti, E. EMBO J. 1994, 13, 4302-4310. For cdc25B, see: Honda, R.; Ohba, Y. Nagata, A.; Okayama, H.; Yasuda, H. FEBS Lett. 1993, 318, 331-334.
17. 11. The ability of rabbit PP1 to dephosphorylate p-nitrophenylphosphate was measured in a buffer containing 20 mM MOPS, pH 7.5, 60 mM 2-mercaptoethanol, 0.1 M NaCl, 1 mg/mL serum albumin, and 50% glycerol. The assays were carried out according to the UBI (Upstate Biotechnology Incorporated) method.