Synthesis of phosphorothioate analogs of phosphatidylinositol 3,4,5-trisphosphate

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 10, 1997, Pages 1231-1234

  Kubiak, Robert J ^a   Bruzik, Karol S ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INOSITOL DERIVATIVE; PHOSPHOROTHIOIC ACID DERIVATIVE; POLYPHOSPHOINOSITIDE;

ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; IN VITRO STUDY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0031579947     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00196-0     Document Type: Article

References (22)

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6. Synthesis of the natural 3-phosphorylated phosphatidylinositols: (a) Falck, J.R.; Abdali, A. in Inositol Phosphates and Derivatives. Synthesis, Biochemistry, and Therapeutic Potential, Reitz, A.B. Ed.; ACS Symp. Ser. 1991, 463, 145;
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17. The 31P NMR spectra are simplified by the debenzylation reaction yielding the persilylated derivatives 16 and 17, where only two diastereomers are present due to chirality at the silylated phosphate group at the 1-position.
18. Bruzik, K.S.; Stec, W.J. J. Org. Chem. 1981, 46, 1618; ibid. 1981, 46, 1625.
19. Bruzik, K.S.; Stec, W.J. J. Org. Chem. 1981, 46, 1618; ibid. 1981, 46, 1625.
20. An analogous method employing DBU/TMS-Cl was used recently for the cleavage of the 2-cyanoethyl phosphate; Evans, D.A.; Gage, J.R.; Leighton, J.L. J. Org. Chem. 1992, 57, 1964.
21. The 1;1 ratio of diastereomers of the product 5 is indicated by the 1H NMR spectrum of the derivative 11.
22. 4 (NH4+): 1H NMR (CDCl3:CD3OD:D2O, 1:1:0.3) δ 0.89 (t, J = 6.7 Hz, 6 H), 1.22-1.38 (m, 48 H), 1.52-1.68 (m, 4 H), 2.29-2.37 (m, 4 H), 3.94-3.99 (m, 1 H), 4.04-4.11 (m, 3 H), 4.18-4.24 (m, 1 H), 4.32-4.37 (m, 1 H), 4.43 (m, 1 H), 4.52 (m, 1 H), 4.82 (m, 1 H), 5.27 (m, 1 H) (the two missing inositol protons are most likely overlapped by the broad OH signal); 31P NMR (CDCl3:CD3OD:D2O, 1:1:0.3) δ -0.61 (1P), 52.4 (2P), 53.2 (1P); ES MS [M-H]+=1097. 5 (NH4+): 1H NMR (CDCl3:CD3OD:D2O, 1:1:0.3) δ 0.89 (t, J = 6,6 Hz, 6H), 1.27 (m, 48 H), 1.51-1.68 (m. 4 H), 2.29-2.36 (m, 4 H), 3.93-4.01 (m, 1 H), 4.03-4.38 (m, 6 H), 4.41-4.46 (m, 1 H), 4.79 (m, 1 H), 5.22-5.34 (m, 1 H); the missing inositol proton is most likely overlapped by a broad OH resonance; 31P NMR (CDCl3:CD3OD:D2O, 1:1:0.3) δ 52.3, (1P), 52.6 (1P), 53.2 (1P), 56.7 (1P); ES MS [M-H]+=1113.