A Regioselective Route to 5-Substituted Isoxazole- and Isoxazoline-3-phos­phonates

Abstract

5-Substituted 3-(diethoxyphosphoryl)isoxazoles and -2-isoxazolines were synthesized regioselectively by 1,3-dipolar cycloaddition of (diethoxyphosphoryl)formonitrile oxide to monosubstituted alkynes and alkenes. By applying this methodology to an N-(tert-butoxycarbonyl)-substituted allylglycine methyl ester, we prepared the precursors of two diastereomeric 3-phosphono-2-isoxazolin-5-yl-substituted amino acids, which are bioisosteres of potent NMDA receptor antagonists.

cycloadditions - regioselectivity - phosphonates - isoxazoles - heterocycles

References

1

On leave from Semmelweis University, Budapest, Hungary

2 Ogawa T, Kurose N, Tanaka S, and Nishi K. inventors; Patent Application WO  2006132197.  ; Chem. Abstr. 2007, 146, 62719

3 Sundermann C, Sundermann B, Holenz J, and Hennies H.-H. inventors; Patent Application WO  2006105945.  ; Chem. Abstr. 2006, 145, 419152

4 Caplan JF. Zheng RJ. Blanchard JS. Vederas JC. Org. Lett.  2000,  2:  3857 

5 Encarnacion RD. Sandoval E. Malmstrom J. Christophersen C. J. Nat. Prod.  2000,  63:  874 

6 Bardhan S. Schmitt DC. Porco JA. Org. Lett.  2006,  8:  927 

7 Ogamino T. Obata R. Tomoda H. Nishiyama S. Bull. Chem. Soc. Jpn.  2006,  79:  134 

8 Baxter EW, Nortey SO, and Reitz AB. inventors; Patent Application WO  2008033513.  ; Chem. Abstr. 2008, 148, 355825

9 Bräuner-Osborne H. Egebjerg J. Nielsen E. Madsen U. Krogsgaard-Larsen P. J. Med. Chem.  2000,  43:  2609 

10 Johansen TN. Stensbøl TB. Nielsen B. Vogensen SB. Frydenvang K. Bräuner-Osborne H. Madsen U. Krogsgaard-Larsen P. Chirality  2001,  13:  523 

11 Brehm L. Greenwood JR. Sløk FA. Holm MM. Nielsen B. Geneser U. Stensbøl TB. Bräuner-Osborne H. Begstrup M. Egebjer J. Krogsgaard-Larsen P. Chirality  2004,  16:  452 

12 Takemoto T. Nakajima T. J. Pharm. Soc. Jpn.  1964,  84:  1183 

13 Takemoto T. Yokobe T. Nakajima T. J. Pharm. Soc. Jpn.  1964,  84:  1186 

14 Lizáraga-Guerra R. López MG. J. Agric. Food Chem.  1996,  44:  2556 

15 Conti P. De Amici M. Roda G. Pinto A. Tamborini L. Madsen U. Nielsen B. Bräuner-Osborne H. De Micheli C. Tetrahedron  2007,  63:  2249 

16 Conti P. De Amici M. Grazioso G. Pinto A. Roda G. Stensbøl TB. Madsen U. Nielsen B. Bräuner-Osborne H. Pellegrini-Giampietro FC. Acher FC. De Micheli C. J. Med. Chem.  2005,  48:  6315 

17 Pinto A. Conti P. De Amici M. Tamborini L. Madsen U. Nielsen B. Christesen T. Bräuner-Osborne H. De Micheli C. J. Med. Chem.  2008,  51:  2311 

18 Conti P. Caligiuri A. Pinto A. Roda G. Tamborini L. Nielsen B. Madsen U. Frydenvang K. Colombo AH. De Micheli C. Eur. J. Med. Chem.  2007,  42:  1059 

19 Akarca US. Curr. Pharm. Des.  2005,  11:  1779 

20 Mukaiyama T. Hoshino T. J. Am. Chem. Soc.  1960,  82:  5339 

21 Caldirola P. De Amici M. De Micheli C. Heterocycles  1985,  23:  2479 

22 Padwa A. 1,3-Dipolar Cycloaddition Chemistry   John Wiley & Sons; New York: 1984. 

23 Christl M. Huisgen R. Sustmann R. Chem. Ber.  1973,  106:  3275 

24 Quan C. Kurth M. J. Org. Chem.  2004,  69:  1470 

25 Sinyashin OG. Romanova IP. Sagitova FR. Pavlov VA. Kovalenko VI. Badeev YV. Azancheev NM. Ill’yasov AV. Chernova AV. Vandyukova II. Mendeleev Commun.  1998,  79 

26 Al-Dulayymi JR. Baird MS. Pavlov V. Kurdjukov AI. Tetrahedron  1996,  52:  8877 

27 Zhang R. Chen J. Synthesis  1990,  817 

28 Sokolov MP. Buzykin BI. Pavlov VA. Zh. Obshch. Khim.  1990,  60:  223 

29 Petrov KA. Chauzov VA. Bogdanov NN. Pastukhova IV. Zh. Obshch. Khim.  1976,  46:  1242 

30 Piotrowska DG. Tetrahedron  2006,  62:  12306 

31 Piotrowska DG. Tetrahedron Lett.  2006,  47:  5363 

32 Savignac P. Iorga B. Modern Phosphonate Chemistry Products   CRC Press; Boca Raton: 2003. 

33 Conti P. De Amici M. Grazioso G. Roda G. Barberis Negra F. Nielsen B. Stensbøl TB. Madsen U. Bräuner-Osborne H. Frydenvang K. De Sarro G. Toma L. De Micheli C. J. Med. Chem.  2004,  47:  6740