Synthetic Tritium Labeling: Reagents and Methodologies

Abstract

This review presents a survey of new high specific activity tritium labeling reagents and methodologies developed in recent years and their applications to tritium labeling chemistry. The review is organized on the basis of reagent type, its development and applications. Emphasis is placed on the synthetic applications of the reagents and techniques that have an exceptionally high capability to produce high specific activity tritium labeled compounds. The focus of this review is on chemical labeling syntheses and does not include heterogeneous/homogeneous metal-catalyzed hydrogen-tritium exchange and biochemical reactions.

• 1 Introduction

• 2 Synthesis and Applications of Tritiated Hydrides

• 2.1 Lithium, Sodium, and Potassium Borotritide Reagents (LiBT₄, NaBT₄, KBT₄)

• 2.2 Lithium Tritide (LiT)

• 2.3 Lithium Supertritide (LiEt₃BT)

• 2.4 Lithium Aluminum Tritide (LiAlT₄)

• 2.5 Lithium Selectride [Li(sec-Bu)₃BT]

• 2.6 Lithium Trimethoxyborotritide [Li(OCH₃)₃BT]

• 2.7 Tritiated [2-(1,3-Dithianyl)]myrtanylborane (MDBT₂)

• 2.8 Tritiated Methylborane (CH₃BT₂)

• 2.9 Tritiated Lithium 9-Boratabicyclo[3.3.1]nonane
  (Li9-BBNT)

• 2.10 Tritiated BoraneTHF Complex (BT₃THF)

• 2.11 Lithium Borotritide (LiBT₄)

• 2.12 Tritiated Schwartz’ Reagent (ZrCp₂ClT)

• 2.13 Tritiated Silanes

• 2.14 Tributyltin tritide (Bu₃SnT)

• 2.15 Tritiated Triacetoxy Sodium Borotritide [NaBT(OAc)₃]

• 3 Synthesis and Applications of Tritiated Water

• 3.1 Tritiated Water (T₂O)

• 3.2 Tritiated Methylene Diiodide (CHTI₂)

• 3.3 Tritiated Diimide (TN=NT)

• 3.4 Tritioolefination

• 3.5 Base-Induced Tritiodesilylation

• 3.6 Fluoride-Induced Tritiodesilylation

• 3.7 Tritiated Diazomethane (CHTN₂)

• 4 Catalytic Tritiations with Tritium Gas

• 4.1 Catalytic Tritiodehalogenation

• 4.2 Heterogeneous Catalytic Tritiations

• 4.3 Homogeneous Catalytic Tritiations

• 5 Tritium Labeling via Organometallic Compounds

• 5.1 Metallation/Reduction with Tritium Gas

• 5.2 Metallation/Reduction with Tritiated Water

• 6 Conclusion

tritiated hydrides - heterogeneous catalytic tritiations - high specific activity -

References

1

Home address: Dr. M. Saljoughian, 44 Wandel Dr., Moraga, CA 94556, USA.

2a Allen J. Isot. Phys. Biomed. Sci.   Vol. 1 Labelled Compounds (Part A):  Buncel E. Jones JR. Elsevier; Amsterdam: 1987.  p.425 

2b Andres H, Morimoto H, and Williams PG. inventors; US Patent  5,186,868. 

3 Evans EA. Tritium and Its Compounds   2nd ed.:  Butterworths; London: 1974.  p.14-15  

4 Evans EA. Warrell DC. Elvidge JA. Jones JR. Handbook of Tritium NMR Spectroscopy and Applications   John Wiley and Sons; Chichester: 1985.  p.23-24  

5 Than C. Morimoto H. Andres H. Williams PG. J. Labelled Compd. Radiopharm.  1996,  38:  693 

6 Zippi EM. Andres H. Morimoto H. Williams PG. Synth. Commun.  1995,  25:  2685 

7 Andres H. Morimoto H. Williams PG. J. Chem. Soc., Chem. Commun.  1990,  627 

8 Andres H. Morimoto H. Williams PG. Proceedings of the 4th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1991   Buncel E. Kabalka GW. Elsevier; Amsterdam: 1992.  p.40 

9 Andres H, Morimoto H, and Williams PG. inventors; US Patent  5,186,868. 

10 Andres H. Morimoto H. Williams PG. Zippi EM. Proceedings of the 5th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1994   Allen J. Voges R. John Wiley and Sons; Chichester: 1995.  p.83 

11 Andres H. Than C. Morimoto H. Williams PG. Proceedings of the 6th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1997   Heys JR. Melillo DG. John WiIey and Sons Ltd; Chichester: 1998.  p.213 

12 Coates RM. Hegde S. Pearce CJ. Proceedings of the International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1982   Duncan WP. Susan AB. Elsevier; Amsterdam: 1983.  p.429 

13 Hegde S. Coates RM. Pearce CJ. J. Chem. Soc., Chem. Commun.  1983,  1484 

14 Priestley ND. Floss HG. Froland WA. Lipscomb JD. Williams PG. Morimoto H. J. Am. Chem. Soc.  1992,  114:  7561 

15 Nguyen H.-HAT. Zhu M. Elliott SJ. Nakagawa KH. Hedman B. Costello AM. Peeples TL. Wilkinson B. Morimoto H. Williams PG. Floss HG. Lidstrom ME. Hodgson KO. Chan SI. Proceedings of the 8th International Symposium on Microbial Growth on C1 Compounds, Lidstrom M. E., Tabita F. R.   Kluwer Academic Publishers; Dordrecht: 1996.  p.150 

16 Wilkinson B. Zhu M. Priestley ND. Nguyen H.-HT. Morimoto H. Williams PG. Chan SI. Floss HG. J. Am. Chem. Soc.  1996,  118:  92 

17 Valentine AM. Wilkinson B. Liu KE. Komar-Panicucci S. Priestley ND. Williams PG. Morimoto H. Floss HG. Lippard SJ. J. Am. Chem. Soc.  1997,  119:  1818 

18 Liu Y.-Y. Thom E. Burger W. Proceedings of the 5th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds 1994   Allen J. Voges R. John Wiley and Sons; Chichester: 1995.  p.93 

19 Olah GA. Ohannesian L. Arvangaghi M. Chem. Rev.  1987,  87:  671 

20 Freer RJ. Day AR. Muthukumaraswamy N. Pinon D. Wu A. Showell HJ. Becker EL. Biochemistry  1982,  21:  257 

21 Strazzolini P. Giumanini AG. Cauci S. Tetrahedron  1990,  46:  1081 

22 Montgomery JA. Thomas J. J. Labelled Compd. Radiopharm.  1978,  15:  727 

23 Burr JG. Brown WG. Heller HE. J. Am. Chem. Soc.  1950,  72:  2560 

24 Saljoughian M. Williams PG. Curr. Pharm. Des.  2000,  6:  1029 

25 Dischino DD. Combrink KD. Doweyko L. Morimoto H. Pearce BC. Williams PG. Yevich JP. J. Labelled Compd. Radiopharm.  1995,  36:  789 

26 Burgos A. Kamenka J.-M. Moustier A.-M. Rousseau B. J. Labelled Compd. Radiopharm.  1991,  29:  1061 

27 Lamotte H. Degeilh F. Neau P. Ripoche P. Rousseau B. J. Labelled Compd. Radiopharm.  1994,  34:  289 

28 Saljoughian M. Morimoto H. Williams PG. Fusion Technol.  1992,  21:  318 

29 Liu Y.-Y. Chen L. J. Labelled Compd. Radiopharm.  1995,  38:  71 

30 Lee S. Morimoto H. Williams PG. J. Labelled Compd. Radiopharm.  1997,  39:  461 

31 Burgos A. Kamenka J.-M. Rousseau B. J. Labelled Compd. Radiopharm.  1991,  29:  1347 

32 Rasset C. Rousseau B. Proceedings of the 5th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds 1994   Allen J. Voges R. John Wiley and Sons; Chichester: 1995.  p.91 

33 Rasset C. Rousseau B. J. Labelled Compd. Radiopharm.  1994,  34:  523 

34 Garmestani K. Link JM. Krohn KA. J. Labelled Compd. Radiopharm.  1990,  28:  1171 

35 Than C. Morimoto H. Andres H. Williams PG. J. Org. Chem.  1995,  60:  7503 

36 Than C. Morimoto H. Andres H. Williams PG. J. Org. Chem.  1996,  61:  8771 

37 Latli B. Than C. Morimoto H. Williams PG. Casida JE. J. Labelled Compd. Radiopharm.  1996,  38:  971 

38 Huguenin PN. Shimma N. J. Labelled Compd. Radiopharm.  1996,  38:  999 

39 Dischino DD. Meanwell NA. Morimoto H. Pearce BC. Than C. Torri AF. Williams PG. Yu K.-L. J. Labelled Compd. Radiopharm.  1999,  42:  1061 

40 Zippi EM. Andres H. Morimoto H. Williams PG. Synth. Commun.  1994,  24:  1037 

41 Neu H. Andres H. J. Labelled Compd. Radiopharm.  1999,  42:  992 

42 Kuivila HG. Synthesis  1970,  499 

43 Neumann WP. Synthesis  1987,  665 

44 Parnes H. Pease J. J. Org. Chem.  1979,  44:  151 

45 Miura K. Ichinose Y. Nozaki K. Fugami K. Oshima K. Utimoto K. Bull. Chem. Soc. Jpn.  1989,  62:  143 

46 Four P. Guibé F. J. Org. Chem.  1981,  46:  4439 

47 Padwa A. Nimmesgern H. Wong GSK. Tetrahedron Lett.  1985,  26:  957 

48 Korth HG. Sustmann R. Gröninger KS. Leisung M. Giese B. J. Org. Chem.  1988,  53:  4364 

49 Barton DHR. McCombie SW. J. Chem. Soc., Perkin Trans. 1  1975,  1574 

50 Robins MJ. Wilson JS. J. Am. Chem. Soc.  1981,  103:  932 

51 Jaiswal DK. Andres H. Morimoto H. Williams PG. J. Chem. Soc., Chem. Commun.  1993,  907 

52 Sugiura S. Tanaka T. Bannai K. Kurozumi S. J. Labelled Compd. Radiopharm.  1991,  29:  1041 

53 Zippi EM. Plourde GW. Satyamurthy N. J. Labelled Compd. Radiopharm.  1995,  36:  361 

54 Saljoughian M. Morimoto H. Williams PG. Than C. Seligman SJ. J. Org. Chem.  1996,  61:  9625 

55 Wichmann J. Huguenin P. Adam G. J. Labelled Compd. Radiopharm.  2000,  43:  1 

56 Robins MJ. Wilson JS. Hansske F. J. Am. Chem. Soc.  1983,  105:  4059 

57 Saljoughian M. Morimoto H. Than C. Williams PG. Proceedings of the 6th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1997   Heys JR. Melillo DG. John WiIey and Sons; Chichester: 1998.  p.193 

58 Saljoughian M. Morimoto H. Than C. Williams PG. Andres H. J. Labelled Compd. Radiopharm.  1998,  41:  1027 

59 Ono N. Kaji A. Synthesis  1986,  693 

60 Barton DHR. Bringmann G. Lamotte G. Motherwell WB. Motherwell RSH. Porter AEA. J. Chem. Soc., Perkin Trans. 1  1980,  2657 

61 Moenius T. Andres H. Acemoglu M. Kohler B. Schnelli P. Zueger C. J. Labelled Compd. Radiopharm.  2000,  43:  113 

62 Curran DP. Kim D. Liu HT. Shen W. J. Am. Chem. Soc.  1988,  110:  5900 

63 Curran DP. Somayajula KV. Yu H. Tetrahedron Lett  1992,  33:  2295 

64 Than C. Morimoto H. Williams PG. Chehade KAH. Andres DA. Spielmann HP. J. Org. Chem.  2001,  66:  3602 

65 Jaiswal DK. Morimoto H. Saljoughian M. Williams PG. Proceedings of the 4th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1991   Buncel E. Kabalka GW. Elsevier; Amsterdam: 1992.  p.46 

66 Saljoughian M. Morimoto H. Williams PG. DeMello N. J. Chem. Soc., Chem. Commun.  1990,  1652 

67 Saljoughian M. Williams PG. Morimoto H. Goodlett DR. Van Breemen RB. J. Chem. Soc., Chem. Commun.  1993,  414 

68 Culf AS. Morimoto H. Williams PG. Lockley WJS. Primrose WU. Jones JR. J. Labelled Compd. Radiopharm.  1996,  38:  373 

69 Saljoughian M. Morimoto H. Than C. Williams PG. Tetrahedron Lett.  1996,  37:  2923 

70 Jaiswal DK. Morimoto H. Saljoughian M. Williams PG. Proceedings of the 4th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1991   Buncel E. Kabalka GW. Elsevier; Amsterdam: 1992.  p.46 

71 Brook AG. Acc. Chem. Res.  1974,  7:  77 

72 Brook AG. Warner CM. Limburg WW. Can. J. Chem.  1967,  45:  1231 

73 Kessar SV. Pure Appl. Chem.  1990,  62:  1397 

74 Pizey JS. N-Bromosuccinimide, Diazomethane, Manganese Dioxide, Raney Nickel in Synthetic Reagents   Vol. 2:  Ellis Horwood Ltd; Chichester: 1974.  p.65 

75 Wurdeman RL. Church KM. Gold B. J. Am. Chem. Soc.  1989,  111:  6408 

76 Gutsche CD. The Reaction of Diazomethane and its Derivatives with Aldehydes and Ketones in Organic Reactions   Vol. 8:  John Wiley and Sons; Chichester: 1954.  p.364 

77 Black TH. Aldrichimica Acta  1983,  16:  3 

78 Saljoughian M. Morimoto H. Rapoport H. Proceedings of the 3rd International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1988   Baillie TA. Jones JR. Elsevier; Amsterdam: 1989.  p.517 

79 Saljoughian M. Morimoto H. Williams PG. J. Chem. Soc., Perkin Trans. 1  1990,  1803 

80 Williams PG. Morimoto H. Saljoughian M. Andres H. Trans. Am. Nucl. Soc.  1989,  60:  34 

81 Jaiswal DK. Morimoto H. Trump EL. Williams PG. Wemmer DE. J. Labelled Compd. Radiopharm.  1996,  38:  743 

82 Highsmith S. Kubinec M. Jaiswal DK. Morimoto H. Williams PG. Wemmer DE. J. Biomol. NMR  1993,  3:  325 

83 Jaiswal DK. Morimoto H. Williams PG. Wemmer DE. Proceedings of the 4th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1991   Buncel E. Kabalka GW. Elsevier; Amsterdam: 1992.  p.448 

84 Saljoughian M. Morimoto H. Williams PG. Rapoport H. Trans. Am. Nucl. Soc.  1987,  55:  39 

85 Saljoughian M. Morimoto H. Williams PG. Rapoport H. J. Labelled Compd. Radiopharm.  1988,  25:  313 

86 O’Neil JP. VanBrocklin HF. Morimoto H. Williams PG. J. Labelled Compd. Radiopharm.  1997,  39:  215 

87 Callaway JC. Morimoto H. Gynther J. Airaksinen MM. Williams PG. J. Labelled Compd. Radiopharm.  1992,  31:  355 

88 Kovalainen JT. Morimoto H. Williams PG. Vepsalainen J. Reijonen A. Gynther J. J. Labelled Compd. Radiopharm.  1995,  36:  1147 

89 Bennani YL. Boehm MF. J. Org. Chem.  1995,  60:  1195 

90 Hammadi A. Meunier G. Tarride J.-L. Menez A. Genet R. Proceedings of the 6th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1997   Heys JR. Melillo DG. John WiIey and Sons Ltd; Chichester: 1998.  p.197 

91 Prestwich GD. Wawrzenczyk C. Proc. Natl. Acad. Sci. U.S.A.  1985,  82:  5290 

92 Seltzman HH. Odear DF. Laudeman CP. Ivy Carroll F. Wyrick CD. J. Labelled Compd. Radiopharm.  1994,  24:  367 

93 Taylor R. Tetrahedron Lett.  1975,  435 

94 Blackburn GM. Flavell AJ. Orgee L. Will JP. Williams GM. J. Chem. Soc., Perkin Trans. 1  1981,  3196 

95 Rapkin E. Steele G. Schavey R. Am. Lab.  1995,  27:  31 

96 Pfanner K. Zeller A. J. Labelled Compd. Radiopharm.  1998,  41:  1033 

97 Lockley WJS. J. Labelled Compd. Radiopharm.  1987,  24:  1509 

98 Kingston LP. Lockley WJS. Mather AN. Wilkinson DJ. Hesk D. Jones JR. Proceedings of the 5th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1994   Allen J. Voges R. John Wiley and Sons; Chichester: 1995.  p.57 

99 Morimoto H. Williams PG. Fusion Technol.  1992,  21:  256