Expedient Total Synthesis of Triciribine and Its Prodrugs

REFERENCES

• Schram , K. H. ; Townsend , L. B. The synthesis of 6-amino-4-methyl-8-(β-D-ribofuranosyl)(4-H, 8-H)pyrrolo-[4,3,2-de]pyrimido[4,5-c]pyridazine, a new tricyclic nucleoside . Tetrahedron Lett. 1971 , 49 , 4757 – 4760 .
   Google Scholar
• Yang , L. ; Dan , H. C. ; Sun , M. ; Liu , Q. ; Sun , X.-M. ; Feldman , R. I. ; Hamilton , A. D. ; Polokoff , M. ; Nicosia , S. V. ; Herlyn , M. ; Sebti , S. M. ; Cheng , J. Q. AKT/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of AKT signaling with antitumor activity in cancer cells overexpressing AKT. Cancer Res. 2004, 64, 4394–4399.
   PubMed Web of Science ®Google Scholar
• Datta , S. R. ; Brunet , A. ; Greenberg , M. E. Cellular survival: A play in three AKTS . Genes Devel. 1999 , 13 , 2905 – 2927 .
   PubMed Web of Science ®Google Scholar
• Cheng , J. Q. ; Nicosia , S. V. AKT signal transduction pathway in oncogenesis . In Encyclopedic Reference of Cancer ; D. Schwab (Ed.); Springer : Berlin , Germany , 2001 ; pp. 35 – 37 .
   Google Scholar
• Sun , M. ; Wang , G. ; Paciga , J. E. ; Feldman , R. I. ; Yuan , Z. Q. ; Ma , X. L. ; Shelley , S. A. ; Jove , R. ; Tsichlis , P. N. ; Nicosia , S. V. ; Cheng , J. Q. AKT1/PKBα kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells . Am. J. Pathol. 2001 , 159 , 431 – 437 .
   PubMed Web of Science ®Google Scholar
• Cheng , J. Q. ; Altomare , D. A. ; Klein , M. A. ; Lee , W.-C. ; Kruh , G. D. ; Lissy , N. A. ; Testa , J. R. Transforming activity and cell cycledependent expression of the AKT2 oncogene: Evidence for a link between cell cycle regulation and oncogenesis . Oncogene 1997 , 14 , 2793 – 2801 .
   PubMed Web of Science ®Google Scholar
• West , K. A. ; Castillo , S. S. ; Dennis , P. A. Activation of the PI3K/AKT pathway and chemotherapeutic resistance . Drug Resist. Update 2002 , 5 , 234 – 248 .
   PubMed Web of Science ®Google Scholar
• O'Connell , M. J. ; Rubin , J. ; Hahn , R. G. ; Kvols , L. K. ; Moertel , C. G. Phase II clinical trial of tricyclic nucleoside phosphate for advanced colorectal cancer . Cancer Treat. Report 1987 , 71 ( 3 ), 333 – 334 .
   PubMedGoogle Scholar
• Mittelman , A. ; Casper , E. S. ; Godwin , T. A. ; Cassidy , C. ; Young , C. W. Phase I study of tricyclic nucleoside phosphate . Cancer Treat. Report 1983 , 67 ( 2 ), 159 – 162 .
   PubMedGoogle Scholar
• Feun , L. G. ; Savaraj , N. ; Bodey , G. P. ; Lu , K. ; Yap , B. S. ; Ajani , J. ; Burgess , M. A. ; Benjamin , R. S. ; McKelvey , E. ; Krakoff , I. Phase I study of tricyclic nucleoside phosphate using a five-day continuous infusion schedule . Cancer Res. 1984 , 44 ( 8 ), 3608 – 3612 .
   PubMed Web of Science ®Google Scholar
• Schilcher , R. B. ; Haas , C. D. ; Samson , M. K. ; Young , J. D. ; Baker , L. H. Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5′-phosphate using a weekly intravenous regimen . Cancer Res. 1986 , 46 ( 6 ), 3147 – 3151 .
   PubMed Web of Science ®Google Scholar
• Feun , L. G. ; Blessing , J. A. ; Barrett , R. J. ; Hanjani , P. A phase II trial of tricyclic nucleoside phosphate in patients with advanced squamous cell carcinoma of the cervix: a gynecologic oncology group study . Am. J. Clin. Oncol. 1993 , 16 ( 6 ), 506 – 508 .
   PubMed Web of Science ®Google Scholar
• Hoffman , K. ; Holmes , F. A. ; Fraschini , G. ; Esparza , L. ; Frye , D. ; Raber , M. N. ; Newman , R. A. ; Hortobagyi , G. N. Phase I–II study: Triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer . Cancer Chemother. Pharmacol. 1996 , 37 ( 3 ), 254 – 258 .
   PubMed Web of Science ®Google Scholar
• Pu , P. ; Kang , C. ; Li , J. ; Jiang , H. ; Cheng , J. The effects of antisense AKT2 RNA on the inhibition of malignant glioma cell growth in vitro and in vivo . J. Neuro-Oncol. 2006 , 76 ( 1 ), 1 – 11 .
   PubMed Web of Science ®Google Scholar
• Jiang , J. G. ; Chen , R. J. ; Xiao , B. ; Yang , S. ; Wang , J. N. ; Wang , Y. ; Cowart , L. A. ; Xiao , X. ; Wang , D. W. ; Xia , Y. Regulation of endothelial nitric-oxide synthase activity through phosphorylation in response to epoxyeicosatrienoic acids . Prostaglandins Other Lipid Mediators 2007 , 82 ( 1–4 ), 162 – 174 .
   PubMed Web of Science ®Google Scholar
• Lindsley , C. W. ; Zhao , Z. ; Leister , W. H. ; Robinson , R. ; Barnett , S. F. ; Defeo-Jones , D. ; Jones , R. E. ; Hartman , G. D. ; Huff , J. R. ; Huber , H. E. ; Duggan , M. E. Allosteric AKT (PKB) inhibitors: Discovery and SAR of isozyme selective inhibitors . Bioorg. Med. Chem. Lett. 2005 , 15 ( 3 ), 761 – 764 .
   PubMed Web of Science ®Google Scholar
• Noble , S. ; Goa , K. L. Adefovir dipivoxil . Drugs 1999 , 58 ( 3 ), 479 – 487 , 488–489 .
   PubMed Web of Science ®Google Scholar
• Tyring , S. ; Barbarash , R. A. ; Nahlik , J. E. ; Cunningham , A. ; Marley , J. ; Heng , M. ; Jones , T. ; Rea , T. ; Boon , R. ; Saltzman , R. Famciclovir for the treatment of acute herpes zoster: Effects on acute disease and postherpetic neuralgia: A randomized, double-blind, placebo-controlled trial. Ann. Internal Med. 1995 , 123 ( 2 ), 89 – 96 .
   PubMed Web of Science ®Google Scholar
• Cihlar , T. ; Birkus , G. ; Greenwalt , D. E. ; Hitchcock , M. J. Tenofovir exhibits low cytotoxicity in various human cell types: Comparison with other nucleoside reverse transcriptase inhibitors. Antiviral Res. 2002, 54 (1), 37–45.
   PubMed Web of Science ®Google Scholar
• Beutner , K. R. Valacyclovir: A review of its antiviral activity, pharmacokinetic properties, and clinical efficacy . Antiviral Res. 1995 , 28 ( 4 ), 281 – 290 .
   PubMed Web of Science ®Google Scholar
• Cocohoba , J. M. ; McNicholl , I. R. Valganciclovir: An advance in cytomegalovirus therapeutics . Annals Pharmacother. 2002 , 36 ( 6 ), 1075 – 1079 .
   PubMed Web of Science ®Google Scholar
• Ganapathy , M. E. ; Huang , W. ; Wang , H. ; Ganapathy , V. ; Leibach , F. H. Valacyclovir: A substrate for the intestianl and renal peptide transporters PEPT1 and PEPT2 . Biochem. Biophys. Res. Commun. 1998 , 246 , 470 – 475 .
   PubMed Web of Science ®Google Scholar
• Han , H. ; de Vrueh , R. L. A. ; Rhie , J. K. ; Covitz , K. Y. ; Smith , P. L. ; Lee , C. ; Oh , D. ; Sadee , W. ; Amidon , G. L. 5′-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter . Pharmaceut. Res. 1998 , 15 ( 8 ), 1154 – 1159 .
   PubMed Web of Science ®Google Scholar
• Balimane , P. V. ; Tamai , I. ; Guo , A. ; Nakanishi , T. ; Kitada , H. ; Leibach , F. H. ; Tsuji , A. ; Sinko , P. J. Direct evidence for peptide transporter (PepT1)–mediated uptake of a nonpeptide prodrug, valacyclovir . Biochem. Biophys. Res. Commun. 1998 , 250 ( 2 ), 246 – 51 .
   PubMed Web of Science ®Google Scholar
• Sugawara , M. ; Huang , W. ; Fei , Y.-J. ; Leibach , F. H. ; Ganapathy , V. ; Ganapathy , M. E. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2 . J. Pharmaceut. Sci. 1999 , 89 ( 2000 ), 781 – 789 .
   Google Scholar
• Tsume , Y. ; Vig , B. S. ; Sun , J. ; Landowski , C. P. ; Hilfinger , J. M. ; Ramachandran , C. ; Amidon , G. L. Enhanced absorption and growth inhibition with amino acid monoester prodrugs of floxuridine by targeting hPEPT1 transporters . Molecules , 2008 , 13 ( 7 ), 1441 – 1454 .
   PubMed Web of Science ®Google Scholar
• Porcari , A. R. ; Townsend , L. B. An improved total synthesis of triciribine: A tricyclic nucleoside with antineoplastic and antiviral properties nucleosides . Nucleotides Nucleic Acids 2004 , 23 ( 1–2 ), 31 – 39 .
   PubMed Web of Science ®Google Scholar
• Swayze , E. E. ; Hinkley , J. M. ; Townsend , L. B. In Nucleic Acid Chemistry: Improved and New Synthetic Procedures, Method, and Techniques, Part IV ; L. B. Townsend , R. S. Tipson (Eds.); Wiley-Interscience : New York , 1991 ; p. 16 .
   Google Scholar
• Porcari , A. R. ; Townsend , L. B. An improved synthesis of the versatile heterocycle, 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine . Synth. Commun. 1998 , 28 ( 20 ), 3835 – 3843 .
   Web of Science ®Google Scholar
• Ellis , G. A. ; Romney-Alexander , T. M. Chem. Rev. 1987 , 87 , 779 .
   Web of Science ®Google Scholar
• Grushin , V. V. ; Alper , H. Chem. Rev. 1994 , 94 , 1074 .
   Web of Science ®Google Scholar
• Sundermeier , M. ; Zapf , A. ; Mutyala , S. ; Baumann , W. ; Sans , J. ; Weiss , S. ; Beller , M. Progress in the palladium-catalyzed cyanation of aryl chlorides . Chem. Eur. J. 2003 , 9 ( 8 ), 1828 – 1836 .
   PubMed Web of Science ®Google Scholar
• Jin , F. ; Confalone , P. N. Palladium-catalyzed cyanation reactions of aryl chlorides . Tetrahedron Lett. 2000 , 41 , 3271 – 3273 .
   Web of Science ®Google Scholar
• Sundermayer , M. ; Zapf , A. ; Beller , M. ; Sans , J. A new palladium catalyst system for the cyanation of aryl chlorides. Tetrahedron Lett. 2001 , 42 , 6707 – 6710 .
   Web of Science ®Google Scholar
• von Koten , G. ; Noltes , J. G. In Comprehensive Organometallic Chemistry ; G. Wilkinson (Ed.); Oxford : Pergamon , 1982 ; vol. 2 , p. 709 .
   Google Scholar
• Shen , W. ; Kim , J.-S. ; Kish , P. E. ; Zhang , J. ; Mitchell , S. ; Gentry , B. G. ; Breitenbach , J. M. ; Drach , J. C. ; Hilfingera , J. Design and synthesis of vidarabine prodrugs as antiviral agents . Bioorg. Med. Chem. Lett. 2009 , 19 ( 3 ), 792 – 796 .
   PubMed Web of Science ®Google Scholar
• (a) McGuigan , C. ; Cahard , D. ; Sheeka , H. M. ; De Clercq , E. ; Balzarini , J. Aryl phosphoramidate derivatives of d4T have improved anti-HIV efficacy in tissue culture and may act by the generation of a novel intracellular metabolite. J. Med. Chem. 1996, 39, 1748–1753. (b) Qiu , Y.-L. ; Ptak , R. G. ; Breitenbach , J. M. ; Lin , J.-S. ; Cheng , Y.-C. ; Drach , J. C. ; Kern , E. R. ; Zemlicka , J. Synthesis and antiviral activity of phosphoralaninate derivatives of methylenecyclopropane analogues of nucleosides. Antiviral Res. 1999, 43, 37–53.
   PubMed Web of Science ®Google Scholar
• Vogel , A. I. ; Tatchell , A. R. ; Furnis , B. S. ; Hannaford , A. J. ; Smith , P. W. G. Vogel's Textbook of Practical Organic Chemistry, , 5th ed. ; Wiley & Sons Inc. : New York , 1989 .
   Google Scholar
• Still , W. C. ; Kahn , M. ; Mitra , A. Rapid chromatographic technique for preparative separations with moderate resolution . J. Org. Chem. 1978 , 43 , 2923 – 2925 .
   Web of Science ®Google Scholar