An improved synthesis of V-PROLI/NO, a cytochrome P450-activated nitric oxide prodrug

Tetrahedron Letters

Volumn 50, Issue 31, 2009, Pages 4545-4548

  Hong, Sam Y ^a   Nandurdikar, Rahul S ^a   Keefer, Larry K ^a   Saavedra, Joseph E ^b   Chakrapani, Harinath ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b SAIC FREDERICK INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

O2 VINYL 1 (PYRROLIDIN 1 YL)DIAZEN 1 IUM 1,2 DIOLATE; PRODRUG; SARCOSINE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LIVER PROTECTION;

EID: 66949156475     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2009.05.089     Document Type: Article

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21. 4. The filtrate was concentrated under reduced pressure and the resulting oil was then purified by silica gel flash chromatography using a mixture of 12→75% EtOAc/hexanes to afford 6 (4.40 g, 16.4 mmol, 75%) as an oil. The spectral features of this material were consistent with the previously published values (Ref. 19).
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23. 3·0.1 EtOAc: C, 45.35; H, 7.10; N, 21.44. Found: C, 45.35, H, 6.93; N, 21.08.
24. 2/ethyl acetate), was conducted; the yield of 2 in such a case was 21%.
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26. 3·0.1 EtOAc: C, 25.85; H, 5.14; N, 16.75; Br, 31.85. Found: C, 25.97; H, 5.14; N, 16.48; Br, 31.76.
27. 3: C, 37.26; H, 6.88; N, 26.07. Found: C, 37.34, H, 6.99; N, 25.91.
28. 4·0.1 EtOAc: C, 35.17; H, 5.48; N, 22.60. Found: C, 35.39, H, 5.48; N, 22.60.
29. 4: C, 44.65; H, 6.09; N, 19.54. Found: C, 44.74; H, 6.10; N, 19.43.
30. Stock solutions (10 mM) of the compounds in DMSO were prepared and diluted in 1 × pH 7.4 phosphate buffered saline (PBS) to a final concentration of 100 μM (10 μL stock solution in DMSO + 990 μL PBS) and incubated at 37 °C in the dark. An Agilent 1100 series HPLC fitted with a C-18 reverse-phase column (Phenomenex Luna 250 × 4.60 mm) operating at 262 nm and run isocratically with acetonitrile:water (75%, v/v) was used to analyze the reaction course. Injections (20 μL) of these solutions were carried out once per day. The data plotted were a mean of three independent experiments.
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