Synthesis of N-Acetoxy-N-benzoyl-2-aminofluorene, an Ultimate Carcinogen by LTA Oxidation of α-Phenyl-N-(2-aminofluorenyl)nitrone, and N-(2′-Deoxyguanosin-8-yl)-2-aminofluorene

Honnaiah Mallesha; Kodagahally R. Ravi Kumar; Kanchugarakoppal S. Rangappa

doi:10.1055/s-2001-18718

PAPER

Synthesis of N-Acetoxy-N-benzoyl-2-aminofluorene, an Ultimate Carcinogen by LTA Oxidation of α-Phenyl-N-(2-aminofluorenyl)nitrone, and N-(2′-Deoxyguanosin-8-yl)-2-aminofluorene

Honnaiah Mallesha, Kodagahally R. Ravi Kumar, Kanchugarakoppal S. Rangappa*
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570 006, India
Fax: +91(821)518835 and +91(821)421263; e-Mail: rangappaks@yahoo.com;

Abstract

All articles of this category

Abstract

The rearrangement of a new α-phenyl-N-(2-aminofluorenyl)nitrone (8) to a new ultimate carcinogen, N-acetoxy-N-benzoyl-2-aminofluorene (9) is achieved in a lead tetraacetate (LTA) oxidation reaction. Compound 9 reacts with deoxyguanosine (dG) at pH 7.0 to give N-(benzoyl)-N-(deoxyguanosin-8-yl)-2-aminofluorene (10). Subsequent debenzoylation with the heterogeneous system (sodium carbonate/methanol) leads to the C8-adduct, N-(2′-deoxyguanosin-8-yl)-2-aminofluorene (11).

Key words

N-acetoxy compound - LTA oxidation - α-phenyl-N-(2-aminofluorene)nitrone - dG adduct, N-(2′-deoxyguanosin-8-yl)-2-aminofluorene

Full Text

References

1a Scott TS. Carcinogenic and Chronic Toxic Hazards of Aromatic Amines Elsevier; Amsterdam: 1962.

1b Clayson DB. Garner RC. Chemical Carcinogens Searle CE. ACS Monograph 173 366; Washington: 1969.

1c King CM. Glowinski IB. EHP Environ. Health Perspect. 1983, 43: 42

1d Lai CC. Miller EC. Miller JA. Liem A. Carcinogenesis 1988, 9: 1295

1e Smith BA. Springfield JR. Gutmann HR. Carcinogenesis 1986, 7: 405

1f Helmick JS. Martin KA. Heinrich JL. Novak M. J. Am. Chem. Soc. 1991, 113: 3459

2a Allaben WT. Weis CC. Fullerton NF. Beland FA. Carcinogenesis 1983, 4: 1067

2b Morris HP. Eyestone WH. J. Natl. Cancer Inst. 1953, 13: 1139

3a Lai CC. Miller EC. Miller JA. Liem A. Carcinogenesis 1988, 9: 1295

3b Allaben WT. King CM. J. Biol. Chem. 1984, 259: 12128

4a In Microsomes and Drug Oxidations Flammang TJ. Kadlubar FF. Taylor and Francis; London: 1985. p.190

4b Flammang TJ. Kadlubar FF. Carcinogenesis 1986, 7: 919

4c Bosold F. Boche G. Angew. Chem., Int. Ed. Engl. 1990, 29: 63

4d Boche G. Ulbrich R. Famulok M. Bosold F. Tetrahedron Lett. 1990, 31: 1689

4e Meier C. Boche G. Tetrahedron Lett. 1990, 31: 1693

5a Scribner JA. Miller JA. Miller EC. Cancer Res. 1970, 30: 1570

5b Kriek E. Chem. Biol. Interact. 1969, 1: 3

5c Patel DJ. Tonelli AF. Biochemistry 1975, 14: 3990

5d Graves DE. Stone MP. Krugh TR. Biochemistry 1985, 24: 7573

6 Weisburger JA. Weisburger EK. Pharmacol. Rev. 1973, 25: 1

7a Novak M. Rangappa KS. J. Org. Chem. 1992, 57: 1285

7b Novak M. Rangappa KS. Manitsas RK. J. Org. Chem. 1993, 58: 7813

7c Novak M. Helmick JS. Oberlies N. Rangappa KS. Clark WM. Swenton JS. J. Org. Chem. 1993, 58: 867

8 Beland FA. Miller DW. Mitchum RK. J. Chem. Soc., Chem. Commum. 1983, 30

9a King CM. Philipps B. Science 1968, 159: 1351

9b King CM. Philipps B. J. Biol. Chem. 1969, 244: 6209

10a Irving CC. Russell LT. Biochemistry 1970, 9: 2471

10b Lotlikar PD. Scribner TD. Miller JA. Miller MC. Life Sci. 1966, 5: 1263

11 Luha L. Biochem. J. 1971, 124: 69

12 Weisburger JH. Fiala ES. Experiental Colon Carcinogenesis CRC Press; Boca Raton: 1979. p.27

13 Mallesha H. Ravi Kumar KR. Mantelingu K. Rangappa KS. Synthesis 2001, 10: 1459

14 Famulok M. Boche G. Angew. Chem., Int. Ed. Engl. 1989, 28: 468

15 Patrick TB. Schield JA. Kirchner DG. J. Org. Chem. 1974, 39: 1758

16

Mallesha H., Ravi Kumar K. R., Vishu Kumar B. K., Mantelingu K., Rangappa K. S.; Proc. Ind. Acad. Sci. (Chem. Sci.) 2001, 113 (4), in press

17a Bamberger E. Brady F. Berischite 1900, 33: 271

17b Baeyer A. Berischite 1874, 7: 1638

18a Splitter JS. Calvin M. J. Org. Chem. 1958, 23: 651

18b Kamlet MJ. Kaplan LA. J. Org. Chem. 1957, 22: 576

18c Shindo H. Umezawa B. Chem. Pharm. Bull. 1962, 10: 492

19a Butler RN. Scott FL. O’Mahony AF. Chem. Rev. 1973, 73: 93

19b Hamer J. Macaluso A. Chem. Rev. 1964, 64: 470

19c Ohta A. Ochai E. Chem. Pharm. Bull. 1962, 10: 1260

19d Ohta A. Ochai E. Chem. Pharm. Bull. 1963, 11: 1586

20 Tamagaki S. Oae S. Bull. Chem. Soc. Jpn. 1970, 43: 1573

21 Galtin L. Davis JC. J. Am. Chem. Soc. 1962, 84: 1464

22 Famulok M. Bosold G. Boche G. Angew. Chem., Int. Ed. Engl. 1989, 28: 337

23 Underwood GR. Price MF. Shapiro R. Carcinogenesis 1988, 9: 1817

24 Kriek E. Miller JA. Juhl U. Miller EC. Biochemistry 1967, 6: 177

25a Bosold F. Boche G. Angew. Chem., Int. Ed. Engl. 1990, 29: 63

25b Kriek E. Westra JG. Carcinogenesis 1980, 1: 459