New strategy for the diastereoselective synthesis of bicyclic 'pre- activated' analogues of cyclophosphamide

Tetrahedron Letters

Volumn 39, Issue 16, 1998, Pages 2315-2318

  Maynard Faure, P ^a   Gonser, C ^a   Vaime, V ^a   Bouchu, D ^a  

^a UNIVERSITÉ LYON 1   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ACETALDEHYDE; ALCOHOL DERIVATIVE; AZIDE; BICYCLO COMPOUND; CYCLOPHOSPHAMIDE DERIVATIVE; DRUG ANALOG;

ARTICLE; CATALYSIS; CHEMICAL REACTION; CYCLIZATION; DIASTEREOISOMER; DRUG ACTIVATION; PHOSPHORYLATION; SYNTHESIS;

EID: 0032537110     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00075-6     Document Type: Article

References (40)

1. 1. Both terms, "activated and pre-activated", refer to compounds which do not need liver biological oxidation and are active in vitro. For reviews on cyclophosphamide see: (a) Hill D. L. A Review of Cyclophosphamide, Thomas C. C. Ed, Springfield, 1975;
2. (b) Zon G. Prog. Med. Chem., 1982, 19, 205-246;
3. (c) Stec W. J. in Organophosphorus Chemistry, vol. 13, 1982, pp 145-174;
4. (d) Brock N. Cancer Res., 1989, 49, 1-7.
5. 2. Borch R. F; Hoye T. R. and Swanson T. A. J. Med. Chem., 1984, 27, 490-494 and references cited herein.
6. 3. Connors T. A.; Cox P. J.; Farmer P. B.; Foster A. B. and Jarman M. Biochem. Pharmacol., 1974, 23, 115-129.
7. 4. (a) Marinello A.; Gurtoo H. L.; Struck R. F. and Paul B. Biochem. Biophys. Res. Commun., 1978, 83, 1347-1353;
8. (b) Cox P. J. Biochem. Pharmacol., 1979, 28, 2045-2049;
9. (c) Brock N.; Stekar J.; Pohl J.; Niemeyer U. and Scheffler G. Arzneim.-Forsch., 1979, 29, 659-661.
10. 5. (a) Niemeyer U.; Engel J.; Hilgard P.; Peukert M.; Pohl J. and Sindermann H. in Progress in Clinical and Medecine, vol. 9, Springer-Verlag, Berlin, 1989, pp 35-60;
11. (b) Borch R. F. and Canute G. W. J. Med Chem., 1991 ,34, 3044-3052;
12. (c) Borch R. F. and Valente R. R. J. Med. Chem., 1991, 34, 3052-3058;
13. (d) Schmidt B. F.; Tang W.-C. and Eisenbrand G. Synthesis, 1992, 701-704;
14. (e) Moon K.-Y; Shirota F. N.; Baturay N. and Kwon C-H J. Med. Chem., 1995, 38, 848-851.
15. 6. Bassam L.; Moreau M. and Bouchu D. Tetrahedron Lett., 1990, 887-890.
16. 7. We thank Dr Hecquet B., Centre Oscar Lambret (Lille, France) for preliminary tests on the 3-[bis(2-chloroethyl)amino]-2-aza-4,10-dioxa-3-phosphabicyclo(4.4.0)decane 3-oxide (T/C = 185%, 50 mg/kg).
17. 8. (a) Effenberger F.; Marer R.; Schonwalder K. H. and Ziegler T. Chem. Ber., 1982, 115, 2766-2782;
18. (b) Hojo M.; Masuda R.; Sakaguchi S. and Takagawa M. Synthesis, 1986, 1016-1017.
19. 9. Tietze L. F.; Meier H. and Voss E. Synthesis, 1988, 274-277.
20. 10. The reaction probably takes place in two successive steps (1,4 addition of the methanolate, then substitution of the trichloromethyl group) both having very similar kinetics since one can sometimes isolate a trace amount of methyl (2,3-dihydro-4-furan)carboxylate. This results from the substitution of the trichloromethyl group, at this stage the insufficiently activated double bond cannot undergo further 1,4 addition.
21. 11. This alcohol was previously prepared starting from γ-butyrolactone: Vader J.; Koopmans R.; De Groot A.; Van Veldhuizen A. and Van der Kerk S. Tetrahedron, 1988, 44, 2663-2674.
22. 1H NMR and CPG. It should be noted that this compound is unstable in the presence of traces of acid.
23. 2,3 = 1.68 Hz).
24. 14. (a) Chan T. H. and Lee S. D. Tetrahedron Lett., 1983, 1225-1228;
25. (b) Kim S.; Park J. H. and Lee S. Tetrahedron Lett., 1989, 6697-6700.
26. 15. Vorbrüggen H. Acc. Chem. Res., 1995, 28, 509-520; Acta Biochim. Pol., 1996, 43, 23-36.
27. 15. Vorbrüggen H. Acc. Chem. Res., 1995, 28, 509-520; Acta Biochim. Pol., 1996, 43, 23-36.
28. 16. Lipshutz B. H.; Hayakawa H.; Kato K.; Lowe R. F. and Stevens K. L. Synthesis, 1994, 1476-1484.
29. 17. Typical procedure for the cyclisation: In a Schlenk reaction vessel placed under argon, the solution of 0.5 g (3.78 mmol) of 9 in 5 mL of anhydrous chloroform containing 4 Å molecular sieves is agitated at -78°C. TMSOTf (58 μL, 0.3 mmol) is added over a period of 5 mn. The reaction mixture is allowed to return to room temperature and further agitated during three hours. 4 mL of buffer solution (pH 7) is then added. After the workup the stereomers 10a and 10b (70% yield) are separated by HPLC on Macherey-Nagel silica gel column with chloroform/methanol (97/3) as eluant. It is noted that the same cyclisation reaction is observed when the phosphorodiamidates are placed in "old" chloroform during two weeks.
30. 18. Full conformational study and configurational assignment by NMR spectroscopy of these bicyclic analogues of cyclophophamide will be published elsewhere.
31. 19. Alanine A. I. D.; Fishwick C. W. G. and Szantay Jr. C. Tetrahedron Lett., 1989, 6777-6780.
32. 20. Maynard-Faure P., Thesis, 1997, Lyon.
33. 21. (a) Niemeyer U; Engel J.; Scheffler G.; Molge K.; Sauerbier D. and Weigert W. Invest. New Drugs, 1984, 2, 133-139;
34. (b) Niemeyer U.; Engel J.; Scheffler G.; Pohl J.; Hagele G. and Krebs B. Phosphorus and Sulfur, 1987, 30, 585-588.
35. 25
36. 23. Tsui F.-P; Brandt J. A. and Zon G. Biochem. Pharmacol., 1979, 28, 367-374.
37. 24. (a) Farmer P. B.; Jarman M.; Facchinetti T.; Pankiewicz K. and Stec W. J. Chem.-Biol. Interactions, 1977, 18, 47-57;
38. (b) Abel G.; Cox P. J.; Farmer P. B.; Haskins N. J.; Jarman M.; Merai K. and Stec W. J Cancer Res., 1978, 38, 2592-2599;
39. (c) Jarman M.; Milsted R. A.; Smyth J. F.; Kinas R. W.; Pankiewicz K. and Stec W. J. Cancer Res. 1979, 39, 2762-2767.
40. 23 rules out the possibilty of racemisation of cyclophosphamide during in vitro liver microsomal metabolism but not of the 4-hydroxycyclophosphamide formed thereafter.